Target Information
| Target General Information | Top | |||||
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| Target ID |
T30081
(Former ID: TTDR00500)
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| Target Name |
Thymidine kinase 1 (TK1)
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| Synonyms |
Thymidine kinase, cytosolic
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| Gene Name |
TK1
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Acute myeloid leukaemia [ICD-11: 2A60] | |||||
| 2 | Human immunodeficiency virus disease [ICD-11: 1C60-1C62] | |||||
| Function |
cytosol, identical protein binding, thymidine kinase activity, zinc ion binding, DNA metabolic process, nucleobase-containing compound metabolic process, protein homotetramerization, pyrimidine nucleoside salvage, thymidine metabolic process
Click to Show/Hide
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| BioChemical Class |
Kinase
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| UniProt ID | ||||||
| EC Number |
EC 2.7.1.21
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| Sequence |
MSCINLPTVLPGSPSKTRGQIQVILGPMFSGKSTELMRRVRRFQIAQYKCLVIKYAKDTR
YSSSFCTHDRNTMEALPACLLRDVAQEALGVAVIGIDEGQFFPDIVEFCEAMANAGKTVI VAALDGTFQRKPFGAILNLVPLAESVVKLTAVCMECFREAAYTKRLGTEKEVEVIGGADK YHSVCRLCYFKKASGQPAGPDNKENCPVPGKPGEAVAARKLFAPQQILQCSPAN Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| ADReCS ID | BADD_A05675 ; BADD_A06627 | |||||
| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 2 Approved Drugs | + | ||||
| 1 | DEOXYCYTIDINE | Drug Info | Approved | Acute myeloid leukaemia | [2], [3] | |
| 2 | Penciclovir | Drug Info | Approved | Human immunodeficiency virus infection | [2], [4] | |
| Clinical Trial Drug(s) | [+] 8 Clinical Trial Drugs | + | ||||
| 1 | TK-DLI | Drug Info | Preregistration | Graft-versus-host disease | [5] | |
| 2 | FV-100 | Drug Info | Phase 3 | Varicella zoster virus infection | [6] | |
| 3 | Radiosensitizer gene therapy | Drug Info | Phase 3 | Pancreatic cancer | [7] | |
| 4 | RP101 | Drug Info | Phase 2/3 | Pancreatic cancer | [8] | |
| 5 | HQK-1004 | Drug Info | Phase 2 | Solid tumour/cancer | [9] | |
| 6 | Ad-OC-hsvTK/valacyclovir | Drug Info | Phase 1 | Prostate cancer | [10] | |
| 7 | Rilapladib | Drug Info | Phase 1 | Cardiovascular disease | [11] | |
| 8 | Thymidine kinase-expressing adenovirus and ganciclovir suicide gene therapy | Drug Info | Phase 1 | Solid tumour/cancer | [12] | |
| Discontinued Drug(s) | [+] 1 Discontinued Drugs | + | ||||
| 1 | Sitimagene ceradenovec | Drug Info | Discontinued in Phase 3 | Brain cancer | [13] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Inhibitor | [+] 35 Inhibitor drugs | + | ||||
| 1 | DEOXYCYTIDINE | Drug Info | [14] | |||
| 2 | Penciclovir | Drug Info | [1] | |||
| 3 | FV-100 | Drug Info | [16] | |||
| 4 | Radiosensitizer gene therapy | Drug Info | [17] | |||
| 5 | RP101 | Drug Info | [18] | |||
| 6 | Ad-OC-hsvTK/valacyclovir | Drug Info | [20] | |||
| 7 | Rilapladib | Drug Info | [21] | |||
| 8 | (South)-Methanocarba-Thymidine | Drug Info | [1] | |||
| 9 | 1-[(Z)-4-(triphenylmethoxy)-2-butenyl]thymine | Drug Info | [24] | |||
| 10 | 1-[2-(2-triphenylmethoxyethoxy)ethyl]thymine | Drug Info | [24] | |||
| 11 | 1-[5-(triphenylmethoxy)pentyl]thymine | Drug Info | [24] | |||
| 12 | 1-[6-(triphenylmethoxy)hexyl]thymine | Drug Info | [24] | |||
| 13 | 1-[7-(triphenylmethoxy)heptyl]thymine | Drug Info | [24] | |||
| 14 | 2'-deoxythymidine triphosphate | Drug Info | [1] | |||
| 15 | 2'-Deoxyuridine | Drug Info | [14] | |||
| 16 | 2-phenylamino-9-(4-hydroxy-butyl)-6-oxopurine | Drug Info | [25] | |||
| 17 | 3'-(1,2,3-Triazol-1-yl)-3'-deoxy-beta-D-thymidine | Drug Info | [26] | |||
| 18 | 3-(2-propyn-1-yl)thymidine | Drug Info | [27] | |||
| 19 | 5-Bromothienyldeoxyuridine | Drug Info | [1] | |||
| 20 | 5-Iodo-2'-Deoxyuridine-5'-Monophosphate | Drug Info | [1] | |||
| 21 | 5-propyl-2'-deoxyuridine | Drug Info | [25] | |||
| 22 | 6-(Dihydroxy-Isobutyl)-Thymine | Drug Info | [1] | |||
| 23 | 6-Hydroxypropylthymine | Drug Info | [1] | |||
| 24 | 9-(4-Hydroxybutyl)-N2-Phenylguanine | Drug Info | [1] | |||
| 25 | 9-Hydroxypropyladenine, R-Isomer | Drug Info | [1] | |||
| 26 | 9-Hydroxypropyladenine, S-Isomer | Drug Info | [1] | |||
| 27 | BVDU-MP | Drug Info | [28] | |||
| 28 | Deoxythymidine | Drug Info | [1] | |||
| 29 | Edoxudine | Drug Info | [25] | |||
| 30 | ITdU | Drug Info | [21] | |||
| 31 | L-5-(bromovinyl)deoxyuridine | Drug Info | [25] | |||
| 32 | L-5-iodo-2'-deoxyuridine | Drug Info | [25] | |||
| 33 | N2-(3-trifluoromethylphenyl)guanine | Drug Info | [25] | |||
| 34 | P1-(5'-Adenosyl)P5-(5'-Thymidyl)Pentaphosphate | Drug Info | [18] | |||
| 35 | Thymidine-5'-Phosphate | Drug Info | [1] | |||
| Modulator | [+] 4 Modulator drugs | + | ||||
| 1 | TK-DLI | Drug Info | [15] | |||
| 2 | HQK-1004 | Drug Info | [19] | |||
| 3 | Thymidine kinase-expressing adenovirus and ganciclovir suicide gene therapy | Drug Info | [22] | |||
| 4 | Sitimagene ceradenovec | Drug Info | [23] | |||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "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 | |||||
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| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
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| Target-regulating Transcription Factors | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| Target QSAR Model | ||||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 1 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
| REF 2 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 3 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000912) | |||||
| REF 4 | Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. | |||||
| REF 5 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800023073) | |||||
| REF 6 | ClinicalTrials.gov (NCT02412917) A Comparative Study of FV-100 vs. Valacyclovir for the Prevention of Post-Herpetic Neuralgia. U.S. National Institutes of Health. | |||||
| REF 7 | Clinical pipeline report, company report or official report of Advantagene. | |||||
| REF 8 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800020300) | |||||
| REF 9 | ClinicalTrials.gov (NCT00992732) Study of HQK-1004 and Valganciclovir to Treat Epstein-Barr Virus (EBV) - Positive Lymphoid Malignancies or Lymphoproliferative Disorders. U.S. National Institutes of Health. | |||||
| REF 10 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007778) | |||||
| REF 11 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800018454) | |||||
| REF 12 | ClinicalTrials.gov (NCT00964756) A Study of an Infectivity Enhanced Suicide Gene Expressing Adenovirus for Ovarian Cancer in Patients With Recurrent Ovarian and Other Selected Gynecologic Cancers. U.S. National Institutes of Health. | |||||
| REF 13 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800015264) | |||||
| REF 14 | Species- or isozyme-specific enzyme inhibitors. 5. Differential effects of thymidine substituents on affinity for rat thymidine kinase isozymes. J Med Chem. 1982 Jun;25(6):644-9. | |||||
| REF 15 | Company report (Takara Bio) | |||||
| REF 16 | Specific recognition of the bicyclic pyrimidine nucleoside analogs, a new class of highly potent and selective inhibitors of varicella-zoster virus (VZV), by the VZV-encoded thymidine kinase. Mol Pharmacol. 2002 Feb;61(2):249-54. | |||||
| REF 17 | Pronounced antitumor effects and tumor radiosensitization of double suicide gene therapy. Clin Cancer Res. 1997 Nov;3(11):2081-8. | |||||
| REF 18 | DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41. | |||||
| REF 19 | Induction of the Epstein-Barr virus thymidine kinase gene with concomitant nucleoside antivirals as a therapeutic strategy for Epstein-Barr virus-associated malignancies. Curr Opin Oncol. 2001 Sep;13(5):360-7. | |||||
| REF 20 | Phase I dose escalation clinical trial of adenovirus vector carrying osteocalcin promoter-driven herpes simplex virus thymidine kinase in localized and metastatic hormone-refractory prostate cancer. Hum Gene Ther. 2003 Feb 10;14(3):227-41. | |||||
| REF 21 | Trichomonas vaginalis thymidine kinase: purification, characterization and search for inhibitors. Biochem J. 1998 Aug 15;334 ( Pt 1):15-22. | |||||
| REF 22 | Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41. | |||||
| REF 23 | Sitimagene ceradenovec: a gene-based drug for the treatment of operable high-grade glioma. Future Oncol. 2010 Nov;6(11):1691-710. | |||||
| REF 24 | N1-substituted thymine derivatives as mitochondrial thymidine kinase (TK-2) inhibitors. J Med Chem. 2006 Dec 28;49(26):7766-73. | |||||
| REF 25 | Sensitivity of monkey B virus (Cercopithecine herpesvirus 1) to antiviral drugs: role of thymidine kinase in antiviral activities of substrate anal... Antimicrob Agents Chemother. 2007 Jun;51(6):2028-34. | |||||
| REF 26 | 3'-[4-Aryl-(1,2,3-triazol-1-yl)]-3'-deoxythymidine analogues as potent and selective inhibitors of human mitochondrial thymidine kinase. J Med Chem. 2010 Apr 8;53(7):2902-12. | |||||
| REF 27 | Synthesis, in vitro, and in silico evaluation of organometallic technetium and rhenium thymidine complexes with retained substrate activity toward ... J Med Chem. 2008 Nov 13;51(21):6689-98. | |||||
| REF 28 | Crystal structure of varicella zoster virus thymidine kinase. J Biol Chem. 2003 Jul 4;278(27):24680-7. | |||||
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