Target Information
| Target General Information | Top | |||||
|---|---|---|---|---|---|---|
| Target ID |
T09826
(Former ID: TTDNC00422)
|
|||||
| Target Name |
DNA topoisomerase I (TOP1)
|
|||||
| Synonyms |
DNA topoisomerase I
Click to Show/Hide
|
|||||
| Gene Name |
TOP1
|
|||||
| Target Type |
Successful target
|
[1] | ||||
| Disease | [+] 5 Target-related Diseases | + | ||||
| 1 | Bacterial infection [ICD-11: 1A00-1C4Z] | |||||
| 2 | Colorectal cancer [ICD-11: 2B91] | |||||
| 3 | Lung cancer [ICD-11: 2C25] | |||||
| 4 | Ovarian cancer [ICD-11: 2C73] | |||||
| 5 | Solid tumour/cancer [ICD-11: 2A00-2F9Z] | |||||
| Function |
Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(3'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 5'-OH DNA strand. The free DNA strand then rotates around the intact phosphodiester bond on the opposing strand, thus removing DNA supercoils. Finally, in the religation step, the DNA 5'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells. Involved in the circadian transcription of the core circadian clock component ARNTL/BMAL1 by altering the chromatin structure around the ROR response elements (ROREs) on the ARNTL/BMAL1 promoter. Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex.
Click to Show/Hide
|
|||||
| BioChemical Class |
Topoisomerase
|
|||||
| UniProt ID | ||||||
| EC Number |
EC 5.6.2.2
|
|||||
| Sequence |
MSGDHLHNDSQIEADFRLNDSHKHKDKHKDREHRHKEHKKEKDREKSKHSNSEHKDSEKK
HKEKEKTKHKDGSSEKHKDKHKDRDKEKRKEEKVRASGDAKIKKEKENGFSSPPQIKDEP EDDGYFVPPKEDIKPLKRPRDEDDADYKPKKIKTEDTKKEKKRKLEEEEDGKLKKPKNKD KDKKVPEPDNKKKKPKKEEEQKWKWWEEERYPEGIKWKFLEHKGPVFAPPYEPLPENVKF YYDGKVMKLSPKAEEVATFFAKMLDHEYTTKEIFRKNFFKDWRKEMTNEEKNIITNLSKC DFTQMSQYFKAQTEARKQMSKEEKLKIKEENEKLLKEYGFCIMDNHKERIANFKIEPPGL FRGRGNHPKMGMLKRRIMPEDIIINCSKDAKVPSPPPGHKWKEVRHDNKVTWLVSWTENI QGSIKYIMLNPSSRIKGEKDWQKYETARRLKKCVDKIRNQYREDWKSKEMKVRQRAVALY FIDKLALRAGNEKEEGETADTVGCCSLRVEHINLHPELDGQEYVVEFDFLGKDSIRYYNK VPVEKRVFKNLQLFMENKQPEDDLFDRLNTGILNKHLQDLMEGLTAKVFRTYNASITLQQ QLKELTAPDENIPAKILSYNRANRAVAILCNHQRAPPKTFEKSMMNLQTKIDAKKEQLAD ARRDLKSAKADAKVMKDAKTKKVVESKKKAVQRLEEQLMKLEVQATDREENKQIALGTSK LNYLDPRITVAWCKKWGVPIEKIYNKTQREKFAWAIDMADEDYEF Click to Show/Hide
|
|||||
| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| ADReCS ID | BADD_A01146 ; BADD_A05675 | |||||
| HIT2.0 ID | T99XQ3 | |||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Approved Drug(s) | [+] 5 Approved Drugs | + | ||||
| 1 | B-Lactams | Drug Info | Approved | Bacterial infection | [2] | |
| 2 | Belotecan hydrocholoride | Drug Info | Approved | Small-cell lung cancer | [3] | |
| 3 | Irinotecan | Drug Info | Approved | Colorectal cancer | [4], [5] | |
| 4 | Topetecan | Drug Info | Approved | Small-cell lung cancer | [6] | |
| 5 | Topotecan | Drug Info | Approved | Ovarian cancer | [7], [8] | |
| Clinical Trial Drug(s) | [+] 44 Clinical Trial Drugs | + | ||||
| 1 | Camptothecin | Drug Info | Phase 3 | Solid tumour/cancer | [9] | |
| 2 | Datopotamab deruxtecan | Drug Info | Phase 3 | Breast cancer | [10] | |
| 3 | Edotecarin | Drug Info | Phase 3 | Gastric adenocarcinoma | [11] | |
| 4 | Etirinotecan pegol | Drug Info | Phase 3 | Breast cancer | [12] | |
| 5 | Exatecan | Drug Info | Phase 3 | Solid tumour/cancer | [13] | |
| 6 | Karenitecin | Drug Info | Phase 3 | Lung cancer | [14] | |
| 7 | Rubitecan | Drug Info | Phase 3 | Human immunodeficiency virus infection | [15] | |
| 8 | 9-AMINOCAMPTOTHECIN | Drug Info | Phase 2 | Acquired immune deficiency syndrome | [16] | |
| 9 | AR-67 | Drug Info | Phase 2 | Myelodysplastic syndrome | [17] | |
| 10 | Beta-Lapachone | Drug Info | Phase 2 | Solid tumour/cancer | [18] | |
| 11 | CKD602 | Drug Info | Phase 2 | Solid tumour/cancer | [19] | |
| 12 | CRLX101 | Drug Info | Phase 2 | Solid tumour/cancer | [20] | |
| 13 | DIFLOMOTECAN | Drug Info | Phase 2 | Solid tumour/cancer | [21] | |
| 14 | EQ-917 | Drug Info | Phase 2 | Solid tumour/cancer | [22] | |
| 15 | Gimatecan | Drug Info | Phase 2 | Breast cancer | [23] | |
| 16 | LE-SN38 | Drug Info | Phase 2 | Solid tumour/cancer | [24], [25] | |
| 17 | Patritumab deruxtecan | Drug Info | Phase 2 | Breast cancer | [26] | |
| 18 | PEG-SN38 | Drug Info | Phase 2 | Metastatic colorectal cancer | [25], [27] | |
| 19 | Pegamotecan | Drug Info | Phase 2 | Esophageal cancer | [28] | |
| 20 | Polyglutamate camptothecin | Drug Info | Phase 2 | Solid tumour/cancer | [29] | |
| 21 | TLC-388 | Drug Info | Phase 2 | Solid tumour/cancer | [30] | |
| 22 | XR-5000 | Drug Info | Phase 2 | Colorectal cancer | [31] | |
| 23 | DS-7300 | Drug Info | Phase 1/2 | Solid tumour/cancer | [32] | |
| 24 | PEN-866 | Drug Info | Phase 1/2 | Solid tumour/cancer | [33] | |
| 25 | ABI-011 | Drug Info | Phase 1 | Solid tumour/cancer | [34] | |
| 26 | Afeletecan | Drug Info | Phase 1 | Breast cancer | [35] | |
| 27 | CZ-48 | Drug Info | Phase 1 | Solid tumour/cancer | [36] | |
| 28 | DAN-222 | Drug Info | Phase 1 | Breast cancer | [37] | |
| 29 | Daniquidone | Drug Info | Phase 1 | Lymphoma | [38] | |
| 30 | DFP 13318 | Drug Info | Phase 1 | Solid tumour/cancer | [33] | |
| 31 | DRF-1042 | Drug Info | Phase 1 | Solid tumour/cancer | [39] | |
| 32 | DS-6157 | Drug Info | Phase 1 | Gastrointestinal stromal tumour | [40] | |
| 33 | ELOMOTECAN HYDROCHLORIDE | Drug Info | Phase 1 | Solid tumour/cancer | [41] | |
| 34 | Genz-644282 | Drug Info | Phase 1 | Solid tumour/cancer | [42] | |
| 35 | GZ402674 | Drug Info | Phase 1 | Solid tumour/cancer | [43] | |
| 36 | INTOPLICINE | Drug Info | Phase 1 | Solid tumour/cancer | [44] | |
| 37 | IT-141 | Drug Info | Phase 1 | Solid tumour/cancer | [33] | |
| 38 | LMP400 | Drug Info | Phase 1 | Lymphoma | [45] | |
| 39 | LMP744 | Drug Info | Phase 1 | Solid tumour/cancer | [46] | |
| 40 | MLN-576 | Drug Info | Phase 1 | Acute lymphoblastic leukaemia | [47] | |
| 41 | Namitecan | Drug Info | Phase 1 | Solid tumour/cancer | [48] | |
| 42 | Tafluposide | Drug Info | Phase 1 | Solid tumour/cancer | [49] | |
| 43 | XMT-1001 | Drug Info | Phase 1 | Solid tumour/cancer | [50] | |
| 44 | (S)-DRF-1042 | Drug Info | Clinical trial | Bladder cancer | [51] | |
| Discontinued Drug(s) | [+] 13 Discontinued Drugs | + | ||||
| 1 | BECATECARIN | Drug Info | Discontinued in Phase 3 | Solid tumour/cancer | [52] | |
| 2 | Atiratecan | Drug Info | Discontinued in Phase 2 | Colorectal cancer | [53] | |
| 3 | Lurtotecan | Drug Info | Discontinued in Phase 2 | Ovarian cancer | [54] | |
| 4 | NK-611 | Drug Info | Discontinued in Phase 2 | Solid tumour/cancer | [55] | |
| 5 | S-16020-2 | Drug Info | Discontinued in Phase 2 | Solid tumour/cancer | [56] | |
| 6 | DE-310 | Drug Info | Discontinued in Phase 1 | Solid tumour/cancer | [57] | |
| 7 | BE-13793C | Drug Info | Terminated | Solid tumour/cancer | [58] | |
| 8 | BN-80245 | Drug Info | Terminated | Solid tumour/cancer | [59] | |
| 9 | CZ-112 | Drug Info | Terminated | Solid tumour/cancer | [60] | |
| 10 | Datelliptium chloride | Drug Info | Terminated | Breast cancer | [61] | |
| 11 | ED-110 | Drug Info | Terminated | Solid tumour/cancer | [62] | |
| 12 | PIROXANTRONE | Drug Info | Terminated | Solid tumour/cancer | [63] | |
| 13 | TAN-1496 | Drug Info | Terminated | Solid tumour/cancer | [64] | |
| Mode of Action | [+] 7 Modes of Action | + | ||||
| Inhibitor | [+] 63 Inhibitor drugs | + | ||||
| 1 | B-Lactams | Drug Info | [65] | |||
| 2 | Topetecan | Drug Info | [1] | |||
| 3 | Datopotamab deruxtecan | Drug Info | [70] | |||
| 4 | Edotecarin | Drug Info | [11] | |||
| 5 | Etirinotecan pegol | Drug Info | [71] | |||
| 6 | Exatecan | Drug Info | [72] | |||
| 7 | Karenitecin | Drug Info | [73] | |||
| 8 | Rubitecan | Drug Info | [74], [75] | |||
| 9 | 9-AMINOCAMPTOTHECIN | Drug Info | [76] | |||
| 10 | AR-67 | Drug Info | [77] | |||
| 11 | CKD602 | Drug Info | [78] | |||
| 12 | DIFLOMOTECAN | Drug Info | [80] | |||
| 13 | EQ-917 | Drug Info | [81] | |||
| 14 | Gimatecan | Drug Info | [82] | |||
| 15 | LE-SN38 | Drug Info | [83], [84] | |||
| 16 | Patritumab deruxtecan | Drug Info | [85] | |||
| 17 | PEG-SN38 | Drug Info | [86] | |||
| 18 | Pegamotecan | Drug Info | [87] | |||
| 19 | Polyglutamate camptothecin | Drug Info | [9] | |||
| 20 | TLC-388 | Drug Info | [30] | |||
| 21 | DS-7300 | Drug Info | [88] | |||
| 22 | PEN-866 | Drug Info | [33] | |||
| 23 | Afeletecan | Drug Info | [90] | |||
| 24 | CZ-48 | Drug Info | [91] | |||
| 25 | DAN-222 | Drug Info | [92] | |||
| 26 | DFP 13318 | Drug Info | [33] | |||
| 27 | DRF-1042 | Drug Info | [76], [94] | |||
| 28 | DS-6157 | Drug Info | [95] | |||
| 29 | Genz-644282 | Drug Info | [98] | |||
| 30 | IT-141 | Drug Info | [33] | |||
| 31 | LMP400 | Drug Info | [101] | |||
| 32 | LMP744 | Drug Info | [101] | |||
| 33 | Namitecan | Drug Info | [103] | |||
| 34 | XMT-1001 | Drug Info | [105] | |||
| 35 | (S)-DRF-1042 | Drug Info | [99] | |||
| 36 | Atiratecan | Drug Info | [107] | |||
| 37 | Lurtotecan | Drug Info | [99], [108] | |||
| 38 | NK-611 | Drug Info | [109] | |||
| 39 | DE-310 | Drug Info | [111] | |||
| 40 | BN-80245 | Drug Info | [113] | |||
| 41 | CZ-112 | Drug Info | [91] | |||
| 42 | (5Z,9Z)-5,9-heptacosadienoic acid | Drug Info | [119] | |||
| 43 | 10-hydroxycamptothecin | Drug Info | [120] | |||
| 44 | 3,3'-(4-phenylpyridine-2,6-diyl)diphenol | Drug Info | [122] | |||
| 45 | 3-(4-phenyl-2,4'-bipyridin-6-yl)phenol | Drug Info | [122] | |||
| 46 | 3-(4-phenyl-6-(thiophen-2-yl)pyridin-2-yl)-phenol | Drug Info | [122] | |||
| 47 | 3-(4-phenyl-6-(thiophen-3-yl)pyridin-2-yl)-phenol | Drug Info | [122] | |||
| 48 | 3-(6-phenyl-2,4'-bipyridin-4-yl)phenol | Drug Info | [122] | |||
| 49 | 4-(4,6-diphenylpyridin-2-yl)phenol | Drug Info | [122] | |||
| 50 | 4-(6-phenyl-2,4'-bipyridin-4-yl)phenol | Drug Info | [122] | |||
| 51 | 4-hydroxysaprothoquinone | Drug Info | [123] | |||
| 52 | A35566-A | Drug Info | [99] | |||
| 53 | ATI-1150 | Drug Info | [99] | |||
| 54 | CHO793076 | Drug Info | [125] | |||
| 55 | DTS-108 | Drug Info | [99] | |||
| 56 | E-758 | Drug Info | [127] | |||
| 57 | Homocamptothecins (hCPTs) | Drug Info | [128] | |||
| 58 | IDN-5174 | Drug Info | [99] | |||
| 59 | IDN-6384 | Drug Info | [99] | |||
| 60 | MEN-14295 | Drug Info | [99] | |||
| 61 | NSC-341622 | Drug Info | [131] | |||
| 62 | ROSETTACIN | Drug Info | [131] | |||
| 63 | TOPOSTATIN | Drug Info | [132] | |||
| Modulator | [+] 23 Modulator drugs | + | ||||
| 1 | Belotecan hydrocholoride | Drug Info | [66], [67] | |||
| 2 | Irinotecan | Drug Info | [68] | |||
| 3 | Topotecan | Drug Info | [68] | |||
| 4 | Camptothecin | Drug Info | [9], [69] | |||
| 5 | Beta-Lapachone | Drug Info | [18] | |||
| 6 | CRLX101 | Drug Info | [79] | |||
| 7 | XR-5000 | Drug Info | [31] | |||
| 8 | ABI-011 | Drug Info | [89] | |||
| 9 | Daniquidone | Drug Info | [93] | |||
| 10 | ELOMOTECAN HYDROCHLORIDE | Drug Info | [96], [97] | |||
| 11 | GZ402674 | Drug Info | [99] | |||
| 12 | INTOPLICINE | Drug Info | [100] | |||
| 13 | MLN-576 | Drug Info | [47], [102] | |||
| 14 | Tafluposide | Drug Info | [104] | |||
| 15 | BECATECARIN | Drug Info | [106] | |||
| 16 | S-16020-2 | Drug Info | [110] | |||
| 17 | BE-13793C | Drug Info | [112] | |||
| 18 | Datelliptium chloride | Drug Info | [114] | |||
| 19 | ED-110 | Drug Info | [115], [116] | |||
| 20 | PIROXANTRONE | Drug Info | [117] | |||
| 21 | TAN-1496 | Drug Info | [118] | |||
| 22 | CRISNATOL MESILATE | Drug Info | [126] | |||
| 23 | TH-1320 | Drug Info | [99] | |||
| Activator | [+] 1 Activator drugs | + | ||||
| 1 | 2,3-Dimethoxybenzo[i]phenanthridines | Drug Info | [121] | |||
| Binder | [+] 4 Binder drugs | + | ||||
| 1 | 5-hydroxy-1H-indole-3-acetic acid | Drug Info | [124] | |||
| 2 | 7-amino-4-hydroxy-2-naphthalenesulfonic acid | Drug Info | [124] | |||
| 3 | Dibenzo-p-dioxin-2-carboxylic acid | Drug Info | [124] | |||
| 4 | Quinizarin | Drug Info | [124] | |||
| Inducer | [+] 2 Inducer drugs | + | ||||
| 1 | KT6006 | Drug Info | [129] | |||
| 2 | KT6528 | Drug Info | [129] | |||
| Intercalator | [+] 1 Intercalator drugs | + | ||||
| 1 | Nogalamycin | Drug Info | [130] | |||
| Stimulator | [+] 1 Stimulator drugs | + | ||||
| 1 | SER-203 | Drug Info | [99] | |||
| Cell-based Target Expression Variations | Top | |||||
|---|---|---|---|---|---|---|
| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: Topotecan | Ligand Info | |||||
| Structure Description | HUMAN DNA TOPOISOMERASE I (70 KDA) IN COMPLEX WITH THE POISON TOPOTECAN AND COVALENT COMPLEX WITH A 22 BASE PAIR DNA DUPLEX | PDB:1K4T | ||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | Yes | [133] |
| PDB Sequence |
QKWKWWEEER
210 YPEGIKWKFL220 EHKGPVFAPP230 YEPLPENVKF240 YYDGKVMKLS250 PKAEEVATFF 260 AKMLDHEYTT270 KEIFRKNFFK280 DWRKEMTNEE290 KNIITNLSKC300 DFTQMSQYFK 310 AQTEARKQMS320 KEEKLKIKEE330 NEKLLKEYGF340 CIMDNHKERI350 ANFKIEPPGL 360 FRGRGNHPKM370 GMLKRRIMPE380 DIIINCSKDA390 KVPSPPPGHK400 WKEVRHDNKV 410 TWLVSWTENI420 QGSIKYIMLN430 PSSRIKGEKD440 WQKYETARRL450 KKCVDKIRNQ 460 YREDWKSKEM470 KVRQRAVALY480 FIDKLALRAG490 NEKEEGETAD500 TVGCCSLRVE 510 HINLHPELDG520 QEYVVEFDFL530 GKDSIRYYNK540 VPVEKRVFKN550 LQLFMENKQP 560 EDDLFDRLNT570 GILNKHLQDL580 MEGLTAKVFR590 TYNASITLQQ600 QLKELTAPDE 610 NIPAKILSYN620 RANRAVAILC630 NHQRAPPKTF640 EKSMMNLQTK650 IDAKKEQLAD 660 ARRDLKSAKA670 DAKVMKDAKT680 KKVVESKKKA690 VQRLEEQLMK700 LEVQATDREE 710 NKQIALGTSK720 LNLDPRITVA731 WCKKWGVPIE741 KIYNKTQREK751 FAWAIDMADE 761 DYEF
|
|||||
|
|
||||||
| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Camptothecin | Ligand Info | |||||
| Structure Description | Human DNA Topoisomerase I (70 Kda) In Complex With The Poison Camptothecin and Covalent Complex With A 22 Base Pair DNA Duplex | PDB:1T8I | ||||
| Method | X-ray diffraction | Resolution | 3.00 Å | Mutation | Yes | [134] |
| PDB Sequence |
QKWKWWEEER
210 YPEGIKWKFL220 EHKGPVFAPP230 YEPLPENVKF240 YYDGKVMKLS250 PKAEEVATFF 260 AKMLDHEYTT270 KEIFRKNFFK280 DWRKEMTNEE290 KNIITNLSKC300 DFTQMSQYFK 310 AQTEARKQMS320 KEEKLKIKEE330 NEKLLKEYGF340 CIMDNHKERI350 ANFKIEPPGL 360 FRGRGNHPKM370 GMLKRRIMPE380 DIIINCSKDA390 KVPSPPPGHK400 WKEVRHDNKV 410 TWLVSWTENI420 QGSIKYIMLN430 PSSRIKGEKD440 WQKYETARRL450 KKCVDKIRNQ 460 YREDWKSKEM470 KVRQRAVALY480 FIDKLALRAG490 NEKEEGETAD500 TVGCCSLRVE 510 HINLHPELDG520 QEYVVEFDFL530 GKDSIRYYNK540 VPVEKRVFKN550 LQLFMENKQP 560 EDDLFDRLNT570 GILNKHLQDL580 MEGLTAKVFR590 TYNASITLQQ600 QLKELTAPDE 610 NIPAKILSYN620 RANRAVAILC630 NHQRAPPKTF640 EKSMMNLQTK650 IDAKKEQLAD 660 ARRDLKSAKA670 DAKVMKDAKT680 KKVVESKKKA690 VQRLEEQLMK700 LEVQATDREE 710 NKQIALGTSK720 LNLDPRITVA731 WCKKWGVPIE741 KIYNKTQREK751 FAWAIDMADE 761 DYEF
|
|||||
|
|
||||||
| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
|---|---|
|
Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Biological Network Descriptors
|
|
|
There is no similarity protein (E value < 0.005) for this target
|
|
Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
|
| Degree | 13 | Degree centrality | 1.40E-03 | Betweenness centrality | 5.03E-04 |
|---|---|---|---|---|---|
| Closeness centrality | 2.41E-01 | Radiality | 1.42E+01 | Clustering coefficient | 2.18E-01 |
| Neighborhood connectivity | 5.47E+01 | Topological coefficient | 9.88E-02 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
|---|---|
| Drug Property Profile of Target | Top | |
|---|---|---|
| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
|
|
||
| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
|
|
||
| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
|
|
||
| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Co-Targets | Top | |||||
|---|---|---|---|---|---|---|
| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
|---|---|---|---|---|---|---|
| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
|---|---|---|---|---|---|---|
| Target-regulating microRNAs | ||||||
| Target-interacting Proteins | ||||||
| Target Profiles in Patients | Top | |||||
|---|---|---|---|---|---|---|
| Drug Resistance Mutation (DRM) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
|---|---|---|---|---|---|---|
| NetPath Pathway | [+] 1 NetPath Pathways | + | ||||
| 1 | IL2 Signaling Pathway | |||||
| Panther Pathway | [+] 1 Panther Pathways | + | ||||
| 1 | DNA replication | |||||
| PID Pathway | [+] 1 PID Pathways | + | ||||
| 1 | Caspase Cascade in Apoptosis | |||||
| WikiPathways | [+] 1 WikiPathways | + | ||||
| 1 | Integrated Pancreatic Cancer Pathway | |||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 1 | Clinical pipeline report, company report or official report of GlaxoSmithKline (2009). | |||||
| REF 2 | Has nature already identified all useful antibacterial targets Curr Opin Microbiol. 2008 Oct;11(5):387-92. | |||||
| REF 3 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 4 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6823). | |||||
| REF 5 | New drugs for the treatment of cancer, 1990-2001. Isr Med Assoc J. 2002 Dec;4(12):1124-31. | |||||
| REF 6 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 020671. | |||||
| REF 7 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7101). | |||||
| REF 8 | Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. | |||||
| REF 9 | Topoisomerase I inhibitors: camptothecins and beyond. Nat Rev Cancer. 2006 Oct;6(10):789-802. | |||||
| REF 10 | ClinicalTrials.gov (NCT05374512) A Phase 3, Open-label, Randomised Study of Datopotamab Deruxtecan (Dato-DXd) Versus Investigator's Choice of Chemotherapy in Patients Who Are Not Candidates for PD-1/PD-L1 Inhibitor Therapy in First-line Locally Recurrent Inoperable or Metastatic Triple-negative Breast Cancer (TROPION Breast02). U.S.National Institutes of Health. | |||||
| REF 11 | Edotecarin: a novel topoisomerase I inhibitor. Clin Colorectal Cancer. 2005 May;5(1):27-36. | |||||
| REF 12 | ClinicalTrials.gov (NCT01492101) The BEACON Study (Breast Cancer Outcomes With NKTR-102). U.S. National Institutes of Health. | |||||
| REF 13 | ClinicalTrials.gov (NCT00023972) Gemcitabine With or Without Exatecan Mesylate in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer. U.S. National Institutes of Health. | |||||
| REF 14 | ClinicalTrials.gov (NCT00477282) Karenitecin Versus Topotecan in Patients With Advanced Epithelial Ovarian Cancer. U.S. National Institutes of Health. | |||||
| REF 15 | ClinicalTrials.gov (NCT00005869) Nitrocamptothecin Compared With Gemcitabine in Treating Patients With Unresectable Locally Advanced or Metastatic Pancreatic Cancer. U.S. National Institutes of Health. | |||||
| REF 16 | ClinicalTrials.gov (NCT00001427) A Phase II Trial of 72-Hour Continuous IV Infusion of 9-Aminocamptothecin With G-CSF Support in Patients With Advanced Ovarian Cancer Previously Treated With Paclitaxel and Cisplatin. U.S. National Institutes of Health. | |||||
| REF 17 | ClinicalTrials.gov (NCT01124539) Study of AR-67 in Adult Patients With Recurrence of Glioblastoma Multiforme (GBM) or Gliosarcoma. U.S. National Institutes of Health. | |||||
| REF 18 | Cancer therapy with beta-lapachone. Curr Cancer Drug Targets. 2002 Sep;2(3):227-42. | |||||
| REF 19 | ClinicalTrials.gov (NCT00430144) Belotecan (CKD-602) in Recurrent or Progressive Carcinoma of Uterine Cervix. U.S. National Institutes of Health. | |||||
| REF 20 | ClinicalTrials.gov (NCT01803269) Topotecan Hydrochloride or Cyclodextrin-Based Polymer-Camptothecin CRLX101 in Treating Patients With Recurrent Small Cell Lung Cancer. U.S. National Institutes of Health. | |||||
| REF 21 | ClinicalTrials.gov (NCT00080015) Diflomotecan (BN80915) Administered Once Every 3 Weeks in Treating Patients With Sensitive Small Cell Lung Cancer (SCLC). U.S. National Institutes of Health. | |||||
| REF 22 | Phase II study of camtobell inj. (belotecan) in combination with cisplatin in patients with previously untreated, extensive stage small cell lung cancer. Lung Cancer. 2013 Jun;80(3):313-8. | |||||
| REF 23 | A phase II trial of oral gimatecan for recurrent glioblastoma. J Neurooncol. 2013 Feb;111(3):347-53. | |||||
| REF 24 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6925). | |||||
| REF 25 | Randomized phase 2 study of pegylated SN-38 (EZN-2208) or irinotecan plus cetuximab in patients with advanced colorectal cancer. Cancer. 2013 Dec 15;119(24):4223-30. | |||||
| REF 26 | ClinicalTrials.gov (NCT05865990) Multicenter, Single-arm, 3 Cohort, Phase II Trial of HER3-DXd in Patients With Active Brain Metastases From Metastatic Breast Cancer and Non-small Cell Lung Cancer, and in Patients With Leptomeningeal Disease From Advanced Solid Tumors. U.S.National Institutes of Health. | |||||
| REF 27 | ClinicalTrials.gov (NCT01036113) A Phase 2 Study of EZN-2208 in Patients With Metastatic Breast Cancer. U.S. National Institutes of Health. | |||||
| REF 28 | ClinicalTrials.gov (NCT00080002) Efficacy of Pegamotecan (PEG-Camptothecin) in Localized or Metastatic Cancer of the Stomach or Gastroesophageal Junction. U.S. National Institutes of Health. | |||||
| REF 29 | ClinicalTrials.gov (NCT00291837) CT-2106 for the Second Line Treatment of Ovarian Cancer. U.S. National Institutes of Health. | |||||
| REF 30 | Topotecan - A novel topoisomerase I inhibitor: pharmacology and clinical experience. Oncology. 1999;56(1):1-12. | |||||
| REF 31 | Phase II study of XR5000 (DACA) administered as a 120-h infusion in patients with recurrent glioblastoma multiforme. Ann Oncol. 2002 May;13(5):777-80. | |||||
| REF 32 | ClinicalTrials.gov (NCT04145622) Study of DS-7300a in Participants With Advanced Solid Malignant Tumors. U.S. National Institutes of Health. | |||||
| REF 33 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 34 | ClinicalTrials.gov (NCT01163071) A Phase 1 Trial of ABI-011 in Patients With Advanced Solid Tumors or Lymphomas. U.S. National Institutes of Health. | |||||
| REF 35 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800013469) | |||||
| REF 36 | ClinicalTrials.gov (NCT00947739) Phase I and Pharmacology Study of Camptothecin-20-O-Propionate Hydrate (CZ48) in Patients With Solid Tumors or Lymphoma. U.S. National Institutes of Health. | |||||
| REF 37 | ClinicalTrials.gov (NCT05261269) A Dose-escalation Study of the Safety and Pharmacology of DAN-222 in Subjects With Metastatic Breast Cancer. U.S.National Institutes of Health. | |||||
| REF 38 | ClinicalTrials.gov (NCT00450502) Safety of Batracylin in Patients With Solid Tumors and Lymphomas. U.S. National Institutes of Health. | |||||
| REF 39 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800014200) | |||||
| REF 40 | ClinicalTrials.gov (NCT04276415) DS-6157a in Participants With Advanced Gastrointestinal Stromal Tumor (GIST). U.S. National Institutes of Health. | |||||
| REF 41 | ClinicalTrials.gov (NCT01435096) BN80927 in Patients With Advanced Malignant Solid Tumors. U.S. National Institutes of Health. | |||||
| REF 42 | ClinicalTrials.gov (NCT00942799) Dose Escalation Study to Assess the Safety and Tolerability of Genz-644282 in Patients With Solid Tumors. U.S. National Institutes of Health. | |||||
| REF 43 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800037203) | |||||
| REF 44 | ClinicalTrials.gov (NCT00003713) Chemotherapy in Treating Patients With Advanced or Metastatic Solid Tumors. U.S. National Institutes of Health. | |||||
| REF 45 | ClinicalTrials.gov (NCT01794104) Indenoisoquinoline LMP400 for Advanced Solid Tumors and Lymphomas. U.S. National Institutes of Health. | |||||
| REF 46 | ClinicalTrials.gov (NCT03030417) Indenoisoquinoline LMP744 in Adults With Relapsed Solid Tumors and Lymphomas. U.S. National Institutes of Health. | |||||
| REF 47 | In vitro and in vivo characterization of XR11576, a novel, orally active, dual inhibitor of topoisomerase I and II. Anticancer Drugs. 2002 Jan;13(1):15-28. | |||||
| REF 48 | ClinicalTrials.gov (NCT01748019) ST1968 Intravenous (Weekly) in Solid Tumors. U.S. National Institutes of Health. | |||||
| REF 49 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800012192) | |||||
| REF 50 | ClinicalTrials.gov (NCT00455052) A Study of Intravenous XMT-1001 in Patients With Advanced Solid Tumors. U.S. National Institutes of Health. | |||||
| REF 51 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8261). | |||||
| REF 52 | Clinical pipeline report, company report or official report of Exelixis. | |||||
| REF 53 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800024385) | |||||
| REF 54 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004939) | |||||
| REF 55 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002418) | |||||
| REF 56 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004159) | |||||
| REF 57 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800014192) | |||||
| REF 58 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005130) | |||||
| REF 59 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800011416) | |||||
| REF 60 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800011353) | |||||
| REF 61 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001278) | |||||
| REF 62 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002530) | |||||
| REF 63 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004116) | |||||
| REF 64 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004359) | |||||
| REF 65 | Luteolin, an emerging anti-cancer flavonoid, poisons eukaryotic DNA topoisomerase I. Biochem J. 2002 Sep 1;366(Pt 2):653-61. | |||||
| REF 66 | Impact of natural products on developing new anti-cancer agents. Chem Rev. 2009 Jul;109(7):3012-43. | |||||
| REF 67 | Belotecan, new camptothecin analogue, is active in patients with small-cell lung cancer: results of a multicenter early phase II study. Ann Oncol. 2008 Jan;19(1):123-7. | |||||
| REF 68 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. | |||||
| REF 69 | Mechanism of action of camptothecin.Ann N Y Acad Sci.2000;922:1-10. | |||||
| REF 70 | Datopotamab Deruxtecan, a Novel TROP2-directed Antibody-drug Conjugate, Demonstrates Potent Antitumor Activity by Efficient Drug Delivery to Tumor Cells. Mol Cancer Ther. 2021 Dec;20(12):2329-2340. | |||||
| REF 71 | Nonclinical pharmacokinetics and activity of etirinotecan pegol (NKTR-102), a long-acting topoisomerase 1 inhibitor, in multiple cancer models. Cancer Chemother Pharmacol. 2014 Dec;74(6):1125-37. | |||||
| REF 72 | Phase I study of topoisomerase I inhibitor exatecan mesylate (DX-8951f) given as weekly 24-hour infusions three of every four weeks. Clin Cancer Res. 2001 Dec;7(12):3963-70. | |||||
| REF 73 | Characterization of protein kinase chk1 essential for the cell cycle checkpoint after exposure of human head and neck carcinoma A253 cells to a novel topoisomerase I inhibitor BNP1350. Mol Pharmacol.2000 Mar;57(3):453-9. | |||||
| REF 74 | Rubitecan. Expert Opin Investig Drugs. 2006 Jan;15(1):71-9. | |||||
| REF 75 | A Phase I study of 9-nitrocamptothecin given concurrently with capecitabine in patients with refractory, metastatic solid tumors. Cancer. 2003 Jan 1;97(1):148-54. | |||||
| REF 76 | Intraperitoneal topoisomerase-I inhibitors. Preliminary findings with 9-aminocamptothecin. Ann N Y Acad Sci. 2000;922:178-87. | |||||
| REF 77 | Protracted dosing of the lipophilic camptothecin analogue AR-67 in non-small cell lung cancer xenografts and humans. Cancer Chemother Pharmacol. 2014 Jul;74(1):45-54. | |||||
| REF 78 | Antitumor activity of 7-[2-(N-isopropylamino)ethyl]-(20S)-camptothecin, CKD602, as a potent DNA topoisomerase I inhibitor. Arch Pharm Res. 1998 Oct;21(5):581-90. | |||||
| REF 79 | Company report (Ceruleanrx) | |||||
| REF 80 | Diflomotecan, a promising homocamptothecin for cancer therapy. Expert Opin Investig Drugs. 2009 Jan;18(1):69-75. | |||||
| REF 81 | The efficacy and toxicity of belotecan (CKD-602), a camptothericin analogue topoisomerase I inhibitor, in patients with recurrent or refractory epithelial ovarian cancer. J Chemother. 2010 Jun;22(3):197-200. | |||||
| REF 82 | Gimatecan and other camptothecin derivatives poison Leishmania DNA-topoisomerase IB leading to a strong leishmanicidal effect. Biochem Pharmacol. 2013 May 15;85(10):1433-40. | |||||
| REF 83 | Analysis of type of cell death induced by topoisomerase inhibitor SN-38 in human oral squamous cell carcinoma cell lines. Anticancer Res. 2012 Nov;32(11):4823-32. | |||||
| REF 84 | J Clin Oncol (Meeting Abstracts) May 2011 vol. 29 no. 15_suppl 7079 | |||||
| REF 85 | Efficacy and Safety of Patritumab Deruxtecan (HER3-DXd) in EGFR Inhibitor-Resistant, EGFR-Mutated Non-Small Cell Lung Cancer. Cancer Discov. 2022 Jan;12(1):74-89. | |||||
| REF 86 | EZN-2208 (PEG-SN38) overcomes ABCG2-mediated topotecan resistance in BRCA1-deficient mouse mammary tumors. PLoS One. 2012;7(9):e45248. | |||||
| REF 87 | A phase II study of pegylated-camptothecin (pegamotecan) in the treatment of locally advanced and metastatic gastric and gastro-oesophageal junction adenocarcinoma. Cancer Chemother Pharmacol. 2009 Jan;63(2):363-70. | |||||
| REF 88 | Clinical pipeline report, company report or official report of Daiichi Sankyo. | |||||
| REF 89 | Company report (Indena) | |||||
| REF 90 | The fate of camptothecin glycoconjugate: report of a clinical hold during a phase II study of BAY 56-3722 (formerly BAY 38-3441), in patients with recurrent or metastatic colorectal cancer resistant/refractory to irinotecan. Invest New Drugs. 2012 June; 30(3): 1208-1210. | |||||
| REF 91 | Pharmacology of camptothecin esters. Ann N Y Acad Sci. 2000;922:216-23. | |||||
| REF 92 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2023. Adis Insight | |||||
| REF 93 | Pharmacogenetically driven patient selection for a first-in-human phase I trial of batracylin in patients with advanced solid tumors and lymphomas.Cancer Chemother Pharmacol.2013 Oct;72(4):917-23. | |||||
| REF 94 | Safety, tolerability, and pharmacokinetics of a capsule formulation of DRF-1042, a novel camptothecin analog, in refractory cancer patients in a bridging phase I study. J Clin Pharmacol. 2005 Apr;45(4):453-60. | |||||
| REF 95 | Identification and Therapeutic Targeting of GPR20, Selectively Expressed in Gastrointestinal Stromal Tumors, with DS-6157a, a First-in-Class Antibody-Drug Conjugate. Cancer Discov. 2021 Jun;11(6):1508-1523. | |||||
| REF 96 | The dual topoisomerase inhibitor, BN 80927, is highly potent against cell proliferation and tumor growth. Ann N Y Acad Sci. 2000;922:303-5. | |||||
| REF 97 | The homocamptothecin, BN 80927, is a potent topoisomerase I poison and topoisomerase II catalytic inhibitor. Ann N Y Acad Sci. 2000;922:301-2. | |||||
| REF 98 | Genz-644282, a novel non-camptothecin topoisomerase I inhibitor for cancer treatment. Clin Cancer Res. 2011 May 1;17(9):2777-87. | |||||
| REF 99 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2636). | |||||
| REF 100 | Dual topoisomerase I and II inhibition by intoplicine (RP-60475), a new antitumor agent in early clinical trials. Mol Pharmacol. 1993 Oct;44(4):767-74. | |||||
| REF 101 | Targeting Topoisomerase I in the Era of Precision Medicine. Clin Cancer Res. 2019 Nov 15;25(22):6581-6589. | |||||
| REF 102 | Ex vivo characterization of XR11576 (MLN576) against ovarian cancer and other solid tumors. Anticancer Drugs. 2004 Oct;15(9):849-60. | |||||
| REF 103 | Namitecan: a hydrophilic camptothecin with a promising preclinical profile. Curr Med Chem. 2012;19(21):3488-501. | |||||
| REF 104 | Ex vivo effects of the dual topoisomerase inhibitor tafluposide (F 11782) on cells isolated from fresh tumor samples taken from patients with cancer. Anticancer Drugs. 2003 Jul;14(6):467-73. | |||||
| REF 105 | Pharmacokinetics and antitumor efficacy of XMT-1001, a novel, polymeric topoisomerase I inhibitor, in mice bearing HT-29 human colon carcinoma xenografts. Clin Cancer Res. 2012 May 1;18(9):2591-602. | |||||
| REF 106 | Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41. | |||||
| REF 107 | Method development and validation of the simultaneous determination of a novel topoisomerase 1 inhibitor, the prodrug, and the active metabolite in human plasma using column-switching LC-MS/MS, and its application in a clinical trial. J Chromatogr B Analyt Technol Biomed Life Sci. 2011 Nov 15;879(30):3415-22. | |||||
| REF 108 | Phase I and pharmacokinetic study of a low-clearance, unilamellar liposomal formulation of lurtotecan, a topoisomerase 1 inhibitor, in patients with advanced leukemia. Cancer. 2004 Apr 1;100(7):1449-58. | |||||
| REF 109 | DNA topoisomerase II poisons and inhibitors. Cancer Chemother Biol Response Modif. 1997;17:114-31. | |||||
| REF 110 | Cellular resistance to the antitumor DNA topoisomerase II inhibitor S16020-2: importance of the N-[2(Dimethylamino)ethyl]carbamoyl side chain. Mol Pharmacol. 2000 Oct;58(4):709-18. | |||||
| REF 111 | DE-310, a macromolecular prodrug of the topoisomerase-I-inhibitor exatecan (DX-8951), in patients with operable solid tumors. Invest New Drugs. 2005 Aug;23(4):339-47. | |||||
| REF 112 | DOI: 10.1002/3527601783.ch20 | |||||
| REF 113 | BN 80245: An E-ring modified camptothecin with potent antiproliferative and topoisomerase I inhibitory activities. Bioorganic & Medicinal Chemistry Letters Volume 7, Issue 17, 9 September 1997, Pages2235-2238. | |||||
| REF 114 | Toxicity of the antitumoral drug datelliptium in hepatic cells: Use of models in vitro for the prediction of toxicity in vivo. Toxicol In Vitro. 1992 Jul;6(4):295-302. | |||||
| REF 115 | ED-110, a novel indolocarbazole, prevents the growth of experimental tumors in mice. Jpn J Cancer Res. 1993 May;84(5):574-81. | |||||
| REF 116 | Indolocarbazole poisons of human topoisomerase I: regioisomeric analogues of ED-110. Bioorg Med Chem Lett. 1999 Jan 18;9(2):145-50. | |||||
| REF 117 | The displacement of iron(III) from its complexes with the anticancer drugs piroxantrone and losoxantrone by the hydrolyzed form of the cardioprotec... J Inorg Biochem. 1999 Nov-Dec;77(3-4):257-9. | |||||
| REF 118 | TAN-1496 A, C and E, diketopiperazine antibiotics with inhibitory activity against mammalian DNA topoisomerase I. J Antibiot (Tokyo). 1994 Nov;47(11):1202-18. | |||||
| REF 119 | Total synthesis and biological evaluation of (5Z,9Z)-5,9-hexadecadienoic acid, an inhibitor of human topoisomerase I. J Nat Prod. 2002 Nov;65(11):1715-8. | |||||
| REF 120 | Upregulation of p21WAF1/CIP1 in human breast cancer cell lines MCF-7 and MDA-MB-468 undergoing apoptosis induced by natural product anticancer drugs 10-hydroxycamptothecin and camptothecin through p53-dependent and independent pathways. Int J Oncol. 1998 Apr;12(4):793-804. | |||||
| REF 121 | 2,3-Dimethoxybenzo[i]phenanthridines: topoisomerase I-targeting anticancer agents. Bioorg Med Chem. 2003 Feb 20;11(4):521-8. | |||||
| REF 122 | Synthesis, topoisomerase I and II inhibitory activity, cytotoxicity, and structure-activity relationship study of hydroxylated 2,4-diphenyl-6-aryl ... Bioorg Med Chem. 2010 May 1;18(9):3066-77. | |||||
| REF 123 | Bioactive abietane and seco-abietane diterpenoids from Salvia prionitis. J Nat Prod. 2002 Jul;65(7):1016-20. | |||||
| REF 124 | Comparison of responses of DNA topoisomerase I from Candida albicans and human cells to four new agents which stimulate topoisomerase-dependent DNA nicking. FEMS Microbiol Lett. 1996 May 1;138(2-3):105-11. | |||||
| REF 125 | Synthesis of new camptothecin analogs with improved antitumor activities. Bioorg Med Chem Lett. 2009 Apr 1;19(7):2018-21. | |||||
| REF 126 | The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954. | |||||
| REF 127 | Lycobetaine acts as a selective topoisomerase IIbeta poison and inhibits the growth of human tumour cells. Br J Cancer. 2001 November; 85(10): 1585-1591. | |||||
| REF 128 | Homocamptothecins: potent topoisomerase I inhibitors and promising anticancer drugs. Crit Rev Oncol Hematol. 2003 Jan;45(1):91-108. | |||||
| REF 129 | Induction of mammalian DNA topoisomerase I mediated DNA cleavage by antitumor indolocarbazole derivatives. Biochemistry. 1992 Dec 8;31(48):12069-75. | |||||
| REF 130 | Structure, dynamics and hydration of the nogalamycin-d(ATGCAT)2Complex determined by NMR and molecular dynamics simulations in solution. J Mol Biol. 1999 Jul 16;290(3):699-716. | |||||
| REF 131 | Synthesis and biological evaluation of 14-(aminoalkyl-aminomethyl)aromathecins as topoisomerase I inhibitors: investigating the hypothesis of share... Bioorg Med Chem. 2009 Oct 15;17(20):7145-55. | |||||
| REF 132 | Isoaurostatin, a novel topoisomerase inhibitor produced by Thermomonospora alba. J Nat Prod. 2001 Feb;64(2):204-7. | |||||
| REF 133 | The mechanism of topoisomerase I poisoning by a camptothecin analog. Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15387-92. | |||||
| REF 134 | Structures of three classes of anticancer agents bound to the human topoisomerase I-DNA covalent complex. J Med Chem. 2005 Apr 7;48(7):2336-45. | |||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.