Target Information
| Target General Information | Top | |||||
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| Target ID |
T97071
(Former ID: TTDS00441)
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| Target Name |
Glutamate carboxypeptidase II (GCPII)
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| Synonyms |
Pteroylpoly-gamma-glutamate carboxypeptidase; Prostate-specific membrane antigen; PSMA; PSM; NAALADase I; NAALAD1; N-acetylated-alpha-linked acidic dipeptidase I; Membrane glutamate carboxypeptidase; MGCP; Glutamate carboxypeptidase 2; GIG27; Folylpoly-gamma-glutamate carboxypeptidase; Folate hydrolase 1; FOLH; FGCP; Cell growth-inhibiting gene 27 protein
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| Gene Name |
FOLH1
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Diagnostic imaging [ICD-11: N.A.] | |||||
| 2 | Prostate cancer [ICD-11: 2C82] | |||||
| Function |
Has a preference for tri-alpha-glutamate peptides. In the intestine, required for the uptake of folate. In the brain, modulates excitatory neurotransmission through the hydrolysis of the neuropeptide, N-aceylaspartylglutamate (NAAG), thereby releasing glutamate. Involved in prostate tumor progression. Has both folate hydrolase and N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity.
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| BioChemical Class |
Peptidase
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| UniProt ID | ||||||
| EC Number |
EC 3.4.17.21
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| Sequence |
MWNLLHETDSAVATARRPRWLCAGALVLAGGFFLLGFLFGWFIKSSNEATNITPKHNMKA
FLDELKAENIKKFLYNFTQIPHLAGTEQNFQLAKQIQSQWKEFGLDSVELAHYDVLLSYP NKTHPNYISIINEDGNEIFNTSLFEPPPPGYENVSDIVPPFSAFSPQGMPEGDLVYVNYA RTEDFFKLERDMKINCSGKIVIARYGKVFRGNKVKNAQLAGAKGVILYSDPADYFAPGVK SYPDGWNLPGGGVQRGNILNLNGAGDPLTPGYPANEYAYRRGIAEAVGLPSIPVHPIGYY DAQKLLEKMGGSAPPDSSWRGSLKVPYNVGPGFTGNFSTQKVKMHIHSTNEVTRIYNVIG TLRGAVEPDRYVILGGHRDSWVFGGIDPQSGAAVVHEIVRSFGTLKKEGWRPRRTILFAS WDAEEFGLLGSTEWAEENSRLLQERGVAYINADSSIEGNYTLRVDCTPLMYSLVHNLTKE LKSPDEGFEGKSLYESWTKKSPSPEFSGMPRISKLGSGNDFEVFFQRLGIASGRARYTKN WETNKFSGYPLYHSVYETYELVEKFYDPMFKYHLTVAQVRGGMVFELANSIVLPFDCRDY AVVLRKYADKIYSISMKHPQEMKTYSVSFDSLFSAVKNFTEIASKFSERLQDFDKSNPIV LRMMNDQLMFLERAFIDPLGLPDRPFYRHVIYAPSSHNKYAGESFPGIYDALFDIESKVD PSKAWGEVKRQIYVAAFTVQAAAETLSEVA Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T40SWE | |||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Approved Drug(s) | [+] 3 Approved Drugs | + | ||||
| 1 | Capromab | Drug Info | Approved | Prostate cancer | [2], [3], [4] | |
| 2 | Lutetium Lu-177 vipivotide tetraxetan | Drug Info | Approved | Prostate cancer | [5] | |
| 3 | PSMA-11 Ga-68 | Drug Info | Approved | Diagnostic imaging | [6] | |
| Clinical Trial Drug(s) | [+] 40 Clinical Trial Drugs | + | ||||
| 1 | 177-Lu-PSMA-617 | Drug Info | Phase 3 | Prostate cancer | [7] | |
| 2 | BAY 2315497 | Drug Info | Phase 3 | Prostate cancer | [8] | |
| 3 | 99mTc-MIP-1404 | Drug Info | Phase 2 | Prostate cancer | [9] | |
| 4 | ATL101 | Drug Info | Phase 2 | Influenza virus infection | [10] | |
| 5 | G-202 | Drug Info | Phase 2 | Solid tumour/cancer | [11] | |
| 6 | J 591 Lu-177 | Drug Info | Phase 2 | Prostate cancer | [12] | |
| 7 | MLN-591RL | Drug Info | Phase 2 | Prostate cancer | [13] | |
| 8 | 177-Lu-PSMA-R2 | Drug Info | Phase 1/2 | Prostate cancer | [14] | |
| 9 | 177Lu-labelled PSMA-R2 | Drug Info | Phase 1/2 | Prostate cancer | [14] | |
| 10 | 4SCAR-PSMA | Drug Info | Phase 1/2 | Bladder cancer | [15] | |
| 11 | 64Cu-SAR-bisPSMA | Drug Info | Phase 1/2 | Prostate cancer | [16] | |
| 12 | 67Cu-SAR-bisPSMA | Drug Info | Phase 1/2 | Prostate cancer | [17] | |
| 13 | Acapatamab | Drug Info | Phase 1/2 | Prostate cancer | [18] | |
| 14 | CAR-T cells targeting PSMA | Drug Info | Phase 1/2 | Cervical cancer | [19] | |
| 15 | LAVA-1207 | Drug Info | Phase 1/2 | Prostate cancer | [20] | |
| 16 | MLN-2704 | Drug Info | Phase 1/2 | Prostate cancer | [21] | |
| 17 | REGN4336 | Drug Info | Phase 1/2 | Prostate cancer | [22] | |
| 18 | REGN5678 | Drug Info | Phase 1/2 | Prostate cancer | [23] | |
| 19 | 177Lu-labelled CTT-1403 | Drug Info | Phase 1 | Prostate cancer | [24] | |
| 20 | 225Ac-J591 | Drug Info | Phase 1 | Prostate cancer | [25] | |
| 21 | 225Ac-PSMA-617 | Drug Info | Phase 1 | Aggressive cancer | [26] | |
| 22 | 227Th-labelled PSMA-TTC | Drug Info | Phase 1 | Prostate cancer | [27] | |
| 23 | 99mTc-MIP-1405 | Drug Info | Phase 1 | Prostate cancer | [28] | |
| 24 | AMG 160 | Drug Info | Phase 1 | Non-small-cell lung cancer | [29] | |
| 25 | AMG 340 | Drug Info | Phase 1 | Prostate cancer | [30] | |
| 26 | APVO414 | Drug Info | Phase 1 | Prostate cancer | [31] | |
| 27 | Autologous T-cell therapy | Drug Info | Phase 1 | Prostate cancer | [32] | |
| 28 | BAY-1075553 | Drug Info | Phase 1 | Prostate cancer | [33] | |
| 29 | CCW702 | Drug Info | Phase 1 | Prostate cancer | [34] | |
| 30 | CTT1403 | Drug Info | Phase 1 | Prostate cancer | [24] | |
| 31 | GPI-16072 | Drug Info | Phase 1 | Neuropathic pain | [35] | |
| 32 | HPN424 | Drug Info | Phase 1 | Prostate cancer | [36] | |
| 33 | Iofolastat I-124 | Drug Info | Phase 1 | Prostate cancer | [37] | |
| 34 | JNJ-63898081 | Drug Info | Phase 1 | Solid tumour/cancer | [38] | |
| 35 | MIP-1095 | Drug Info | Phase 1 | Prostate cancer | [39] | |
| 36 | MT-112 | Drug Info | Phase 1 | Solid tumour/cancer | [40] | |
| 37 | PSMA CAR-T cell therapy | Drug Info | Phase 1 | Prostate cancer | [41] | |
| 38 | PSMA subunit vaccine | Drug Info | Phase 1 | Prostate cancer | [42] | |
| 39 | PSMA-targeted tubulysin B conjugates | Drug Info | Phase 1 | Prostate cancer | [43] | |
| 40 | PSMA-VRP | Drug Info | Phase 1 | Prostate cancer | [44] | |
| Discontinued Drug(s) | [+] 1 Discontinued Drugs | + | ||||
| 1 | MDX-070 | Drug Info | Discontinued in Phase 2 | Prostate cancer | [45] | |
| Preclinical Drug(s) | [+] 1 Preclinical Drugs | + | ||||
| 1 | IRX-4 | Drug Info | Preclinical | Prostate cancer | [46] | |
| Mode of Action | [+] 6 Modes of Action | + | ||||
| Binder | [+] 1 Binder drugs | + | ||||
| 1 | PSMA-11 Ga-68 | Drug Info | [6] | |||
| Agonist | [+] 2 Agonist drugs | + | ||||
| 1 | 177-Lu-PSMA-617 | Drug Info | [48] | |||
| 2 | 177-Lu-PSMA-R2 | Drug Info | [53] | |||
| Modulator | [+] 9 Modulator drugs | + | ||||
| 1 | 99mTc-MIP-1404 | Drug Info | [49] | |||
| 2 | ATL101 | Drug Info | [50] | |||
| 3 | J 591 Lu-177 | Drug Info | [12] | |||
| 4 | 99mTc-MIP-1405 | Drug Info | [49] | |||
| 5 | BAY-1075553 | Drug Info | [67] | |||
| 6 | PSMA-targeted tubulysin B conjugates | Drug Info | [76] | |||
| 7 | 99mTc-MIP-1340 | Drug Info | [75] | |||
| 8 | CTT-54 | Drug Info | [75] | |||
| 9 | MDX-1147 | Drug Info | [75] | |||
| Inhibitor | [+] 43 Inhibitor drugs | + | ||||
| 1 | G-202 | Drug Info | [51] | |||
| 2 | REGN5678 | Drug Info | [59] | |||
| 3 | AMG 160 | Drug Info | [64] | |||
| 4 | APVO414 | Drug Info | [65] | |||
| 5 | CTT1403 | Drug Info | [69] | |||
| 6 | GPI-16072 | Drug Info | [70] | |||
| 7 | Iofolastat I-124 | Drug Info | [72] | |||
| 8 | JNJ-63898081 | Drug Info | [73] | |||
| 9 | MIP-1095 | Drug Info | [74] | |||
| 10 | 2-(2-carboxy-5-mercaptopentyl)benzoic acid | Drug Info | [80] | |||
| 11 | 2-(2-carboxy-7-mercaptoheptyl)benzoic acid | Drug Info | [80] | |||
| 12 | 2-(2-Hydroxycarbamoyl-ethyl)-pentanedioic acid | Drug Info | [81] | |||
| 13 | 2-(2-Mercapto-ethyl)-pentanedioic acid | Drug Info | [82] | |||
| 14 | 2-(2-Phosphonooxy-ethyl)-pentanedioic acid | Drug Info | [82] | |||
| 15 | 2-(3-carbamoylbenzyl)-5-mercaptopentanoic acid | Drug Info | [80] | |||
| 16 | 2-(3-carboxybenzyl)succinic acid | Drug Info | [80] | |||
| 17 | 2-(3-cyanobenzyl)-5-mercaptopentanoic acid | Drug Info | [80] | |||
| 18 | 2-(3-Hydroxycarbamoyl-propyl)-pentanedioic acid | Drug Info | [81] | |||
| 19 | 2-(3-Mercapto-propyl)-pentanedioic acid | Drug Info | [82] | |||
| 20 | 2-(3-Methylsulfanyl-propyl)-pentanedioic acid | Drug Info | [82] | |||
| 21 | 2-(4-Mercapto-butyl)-pentanedioic acid | Drug Info | [82] | |||
| 22 | 2-(5-Mercapto-pentyl)-pentanedioic acid | Drug Info | [82] | |||
| 23 | 2-benzyl-5-mercaptopentanoic acid | Drug Info | [80] | |||
| 24 | 2-Hydroxycarbamoyl-pentanedioic acid | Drug Info | [81] | |||
| 25 | 2-Hydroxycarbamoylmethyl-pentanedioic acid | Drug Info | [81] | |||
| 26 | 2-Mercapto-pentanedioic acid | Drug Info | [82] | |||
| 27 | 2-Mercaptomethyl-pentanedioic acid | Drug Info | [82] | |||
| 28 | 2-Phosphonooxy-pentanedioic acid | Drug Info | [82] | |||
| 29 | 2-PMPA | Drug Info | [83], [84] | |||
| 30 | 3-(1-carboxy-4-mercaptobutoxy)benzoic acid | Drug Info | [80] | |||
| 31 | 3-(2-carbamoyl-5-mercaptopentyl)benzoic acid | Drug Info | [80] | |||
| 32 | 3-(2-carboxy-3-mercaptopropyl)benzoic acid | Drug Info | [80] | |||
| 33 | 3-(2-carboxy-3-phosphonopropyl)benzoic acid | Drug Info | [80] | |||
| 34 | 3-(2-carboxy-4-mercaptobutyl)benzoic acid | Drug Info | [80] | |||
| 35 | 3-(2-carboxy-5-mercaptopentyl)benzoic acid | Drug Info | [80] | |||
| 36 | 3-(2-carboxy-6-mercaptohexyl)benzoic acid | Drug Info | [80] | |||
| 37 | 3-[(1-carboxy-4-mercaptobutyl)thio]benzoic acid | Drug Info | [80] | |||
| 38 | 4-(2-carboxy-5-mercaptopentyl)benzoic acid | Drug Info | [80] | |||
| 39 | 5-Mercapto-pentanoic acid | Drug Info | [82] | |||
| 40 | MIP-1375 | Drug Info | [75] | |||
| 41 | PGI-02749 | Drug Info | [75] | |||
| 42 | PMID15027864C8d | Drug Info | [85] | |||
| 43 | [3H]quisqualate | Drug Info | [86] | |||
| CAR-T-Cell-Therapy | [+] 2 CAR-T-Cell-Therapy drugs | + | ||||
| 1 | 4SCAR-PSMA | Drug Info | [15] | |||
| 2 | CAR-T cells targeting PSMA | Drug Info | [19] | |||
| Immunomodulator (Immunostimulant) | [+] 1 Immunomodulator (Immunostimulant) drugs | + | ||||
| 1 | IRX-4 | Drug Info | [79] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: L-aspartic acid | Ligand Info | |||||
| Structure Description | A high resolution structure of human glutamate carboxypeptidase II (GCPII) His475Tyr variant in complex with glutamic acid | PDB:4MCS | ||||
| Method | X-ray diffraction | Resolution | 1.83 Å | Mutation | Yes | [87] |
| PDB Sequence |
KHNMKAFLDE
64 LKAENIKKFL74 YNFTQIPHLA84 GTEQNFQLAK94 QIQSQWKEFG104 LDSVELAHYD 114 VLLSYPNKTH124 PNYISIINED134 GNEIFNTSLF144 EPPPPGYENV154 SDIVPPFSAF 164 SPQGMPEGDL174 VYVNYARTED184 FFKLERDMKI194 NCSGKIVIAR204 YGKVFRGNKV 214 KNAQLAGAKG224 VILYSDPADY234 FAPGVKSYPD244 GWNLPGGGVQ254 RGNILNLNGA 264 GDPLTPGYPA274 NEYAYRRGIA284 EAVGLPSIPV294 HPIGYYDAQK304 LLEKMGGSAP 314 PDSSWRGSLK324 VPYNVGPGFT334 GNFSTQKVKM344 HIHSTNEVTR354 IYNVIGTLRG 364 AVEPDRYVIL374 GGHRDSWVFG384 GIDPQSGAAV394 VHEIVRSFGT404 LKKEGWRPRR 414 TILFASWDAE424 EFGLLGSTEW434 AEENSRLLQE444 RGVAYINADS454 SIEGNYTLRV 464 DCTPLMYSLV474 YNLTKELKSP484 DEGFEGKSLY494 ESWTKKSPSP504 EFSGMPRISK 514 LGSGNDFEVF524 FQRLGIASGR534 ARYTKNNKFS547 GYPLYHSVYE557 TYELVEKFYD 567 PMFKYHLTVA577 QVRGGMVFEL587 ANSIVLPFDC597 RDYAVVLRKY607 ADKIYSISMK 617 HPQEMKTYSV627 SFDSLFSAVK637 NFTEIASKFS647 ERLQDFSNPI659 VLRMMNDQLM 669 FLERAFIDPL679 GLPDRPFYRH689 VIYAPSSHNK699 YAGESFPGIY709 DALFDIESKV 719 DPSKAWGEVK729 RQIYVAAFTV739 QAAAETLSEV749 A
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| Ligand Name: L-methionine | Ligand Info | |||||
| Structure Description | membrane-bound glutamate carboxypeptidase II (GCPII) with bound methionine | PDB:2CIJ | ||||
| Method | X-ray diffraction | Resolution | 2.40 Å | Mutation | No | [88] |
| PDB Sequence |
NMKAFLDELK
66 AENIKKFLYN76 FTQIPHLAGT86 EQNFQLAKQI96 QSQWKEFGLD106 SVELAHYDVL 116 LSYPNKTHPN126 YISIINEDGN136 EIFNTSLFEP146 PPPGYENVSD156 IVPPFSAFSP 166 QGMPEGDLVY176 VNYARTEDFF186 KLERDMKINC196 SGKIVIARYG206 KVFRGNKVKN 216 AQLAGAKGVI226 LYSDPADYFA236 PGVKSYPDGW246 NLPGGGVQRG256 NILNLNGAGD 266 PLTPGYPANE276 YAYRRGIAEA286 VGLPSIPVHP296 IGYYDAQKLL306 EKMGGSAPPD 316 SSWRGSLKVP326 YNVGPGFTFS338 TQKVKMHIHS348 TNEVTRIYNV358 IGTLRGAVEP 368 DRYVILGGHR378 DSWVFGGIDP388 QSGAAVVHEI398 VRSFGTLKKE408 GWRPRRTILF 418 ASWDAEEFGL428 LGSTEWAEEN438 SRLLQERGVA448 YINADSSIEG458 NYTLRVDCTP 468 LMYSLVHNLT478 KELKSPDEGF488 EGKSLYESWT498 KKSPSPEFSG508 MPRISKLGSG 518 NDFEVFFQRL528 GIASGRARYT538 KNFSGYPLYH553 SVYETYELVE563 KFYDPMFKYH 573 LTVAQVRGGM583 VFELANSIVL593 PFDCRDYAVV603 LRKYADKIYS613 ISMKHPQEMK 623 TYSVSFDSLF633 SAVKNFTEIA643 SKFSERLQDF653 DKSNPIVLRM663 MNDQLMFLER 673 AFIDPLGLPD683 RPFYRHVIYA693 PSSHNKYAGE703 SFPGIYDALF713 DIESKVDPSK 723 AWGEVKRQIY733 VAAFTVQAAA743 ETLSEVA
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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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).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
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
Human Pathway Affiliation
Biological Network Descriptors
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| Protein Name | Pfam ID | Percentage of Identity (%) | E value |
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| #N/A | 88.235 (30/34) | 3.84E-11 | |
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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.
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Alanine, aspartate and glutamate metabolism | hsa00250 | Affiliated Target |
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| Class: Metabolism => Amino acid metabolism | Pathway Hierarchy | ||
| Vitamin digestion and absorption | hsa04977 | Affiliated Target |
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| Class: Organismal Systems => Digestive system | Pathway Hierarchy | ||
| Degree | 1 | Degree centrality | 1.07E-04 | Betweenness centrality | 0.00E+00 |
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| Closeness centrality | 1.07E-04 | Radiality | 3.98E-03 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 1.00E+00 | Topological coefficient | . | Eccentricity | 1 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| 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 | ||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 3 KEGG Pathways | + | ||||
| 1 | Alanine, aspartate and glutamate metabolism | |||||
| 2 | Metabolic pathways | |||||
| 3 | Vitamin digestion and absorption | |||||
| NetPath Pathway | [+] 2 NetPath Pathways | + | ||||
| 1 | TCR Signaling Pathway | |||||
| 2 | TNFalpha Signaling Pathway | |||||
| Reactome | [+] 1 Reactome Pathways | + | ||||
| 1 | Amino acid synthesis and interconversion (transamination) | |||||
| WikiPathways | [+] 1 WikiPathways | + | ||||
| 1 | One Carbon Metabolism | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Synergistic value of single-photon emission computed tomography/computed tomography fusion to radioimmunoscintigraphic imaging of prostate cancer. Semin Nucl Med. 2007 Jan;37(1):17-28. | |||||
| REF 2 | 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: 6878). | |||||
| REF 3 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 4 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (BLA) 103608. | |||||
| REF 5 | FDA Approved Drug Products from FDA Official Website. 2022. Application Number: 215833. | |||||
| REF 6 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020 | |||||
| REF 7 | ClinicalTrials.gov (NCT03511664) Study of 177Lu-PSMA-617 In Metastatic Castrate-Resistant Prostate Cancer (VISION). U.S. National Institutes of Health. | |||||
| REF 8 | ClinicalTrials.gov (NCT05204927) A Multi-Center, Open-Label, Randomized Phase 3 Trial Comparing the Safety and Efficacy of 177Lu-PSMA-I&T Versus Hormone Therapy in Patients With Metastatic Castration-Resistant Prostate Cancer. U.S.National Institutes of Health. | |||||
| REF 9 | ClinicalTrials.gov (NCT01667536) A Phase 2 Diagnostic Imaging Study With 99mTc-MIP-1404 in Men With High-Risk Prostate Cancer Scheduled for Radical Prostatectomy (RP) and Extended Pelvic Lymph Node Dissection (EPLND) Compared to Histopathology. U.S. National Institutes of Health. | |||||
| REF 10 | Clinical pipeline report, company report or official report of Atlab pharma. | |||||
| REF 11 | ClinicalTrials.gov (NCT01777594) Study of G-202 as Second-Line Therapy Following Sorafenib in Hepatocellular Carcinoma. U.S. National Institutes of Health. | |||||
| REF 12 | Phase II study of Lutetium-177-labeled anti-prostate-specific membrane antigen monoclonal antibody J591 for metastatic castration-resistant prostate cancer. Clin Cancer Res. 2013 Sep 15;19(18):5182-91. | |||||
| REF 13 | ClinicalTrials.gov (NCT00195039) Treatment With Radiolabeled Monoclonal Antibody HuJ591-GS (177Lu-J591) in Patients With Metastatic Prostate Cancer. U.S. National Institutes of Health. | |||||
| REF 14 | ClinicalTrials.gov (NCT03490838) 177Lu-PSMA-R2 in Patients With PSMA Positive Progressive, Metastatic, Castration Resistant Prostate Cancer (PROter). U.S. National Institutes of Health. | |||||
| REF 15 | ClinicalTrials.gov (NCT03185468) Intervention of Bladder Cancer by CAR-T | |||||
| REF 16 | ClinicalTrials.gov (NCT05249127) 64Cu-SAR-bisPSMA Positron Emission Tomography: A Phase 1/2 Study of Participants With Biochemical Recurrence of Prostate Cancer. U.S.National Institutes of Health. | |||||
| REF 17 | ClinicalTrials.gov (NCT04868604) A Phase I/IIa Theranostic Study of 64Cu-SAR-bisPSMA and 67Cu-SAR-bisPSMA for Identification and Treatment of PSMA-expressing Metastatic Castrate Resistant Prostate Cancer. U.S.National Institutes of Health. | |||||
| REF 18 | ClinicalTrials.gov (NCT04631601) A Master Protocol Evaluating the Safety and Efficacy of Therapies for Metastatic Castration-resistant Prostate Cancer (mCRPC). U.S.National Institutes of Health. | |||||
| REF 19 | ClinicalTrials.gov (NCT03356795) Intervention of CAR-T Against Cervical Cancer | |||||
| REF 20 | ClinicalTrials.gov (NCT05369000) Phase 1/2a Open-label Trial to Evaluate the Safety, Tolerability, PK, PD, Immunogenicity, and Antitumor Activity of LAVA-1207, a PSMA-targeting Bispecific gamma-delta-T Cell Engager, in Patients With Therapy Refractory mCRPC. U.S.National Institutes of Health. | |||||
| REF 21 | ClinicalTrials.gov (NCT00070837) MLN2704 in Subjects With Metastatic Androgen-Independent Prostate Cancer. U.S. National Institutes of Health. | |||||
| REF 22 | ClinicalTrials.gov (NCT05125016) Phase 1/2 Study of REGN4336 (a PSMAXCD3 Bispecific Antibody) Administered Alone or in Combination With Cemiplimab in Patients With Metastatic Castration-Resistant Prostate Cancer. U.S.National Institutes of Health. | |||||
| REF 23 | ClinicalTrials.gov (NCT03972657) Study of REGN5678 (Anti-PSMAxCD28) With Cemiplimab (Anti-PD-1) in Patients With Metastatic Castration-resistant Prostate Cancer. U.S. National Institutes of Health. | |||||
| REF 24 | ClinicalTrials.gov (NCT03822871) A Trial of CTT1403 for Metastatic Castration Resistant Prostate Cancer. U.S. National Institutes of Health. | |||||
| REF 25 | ClinicalTrials.gov (NCT03276572) Phase I Dose-Escalation Trial of 225Ac-J591 in Patients With Metastatic Castration-Resistant Prostate Cancer. U.S.National Institutes of Health. | |||||
| REF 26 | ClinicalTrials.gov (NCT04597411) AcTION: A Phase I Study of [225Ac]Ac-PSMA-617 in Men With PSMA-positive Prostate Cancer With or Without Prior [177Lu]Lu-PSMA-617 Radioligand Therapy. U.S.National Institutes of Health. | |||||
| REF 27 | ClinicalTrials.gov (NCT03724747) Study to Evaluate the Safety, Tolerability,Pharmacokinetics, and Antitumor Activity of a Thorium-227 Labeled Antibody-chelator Conjugate Alone and in Combination With Darolutamide, in Patients With Metastatic Castration Resistant Prostate Cancer. U.S. National Institutes of Health. | |||||
| REF 28 | ClinicalTrials.gov (NCT01261754) A Study of 99mTc-MIP-1404 and 99mTc-MIP-1405 in Patients With Metastatic Prostate Adenocarcinoma and Healthy Volunteers. U.S. National Institutes of Health. | |||||
| REF 29 | ClinicalTrials.gov (NCT04822298) Study of AMG 160 in Subjects With Non-Small Cell Lung Cancer. U.S. National Institutes of Health. | |||||
| REF 30 | ClinicalTrials.gov (NCT04740034) A Multicenter, Phase 1, Open-label, Dose-escalation and Expansion Study of AMG 340, a Bispecific Antibody Targeting PSMA in Subjects With Metastatic Castrate-Resistant Prostate Carcinoma. U.S.National Institutes of Health. | |||||
| REF 31 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 32 | Clinical application of genetically modified T cells in cancer therapy. Clin Transl Immunology. 2014 May 16;3(5):e16. | |||||
| REF 33 | Phase I Study: BAY 1075553 PET/CT in Staging and Re - Staging of Prostate Cancer Patients - Comparison with 18F-Choline PET/CT. World Molecular Imaging Society. September 20, 2013 | |||||
| REF 34 | ClinicalTrials.gov (NCT04077021) First-in-human Study of CCW702 in Patients With Metastatic Castration Resistant Prostate Cancer. U.S. National Institutes of Health. | |||||
| REF 35 | Emerging disease-modifying therapies for the treatment of motor neuron disease/amyotropic lateral sclerosis. Expert Opin Emerg Drugs. 2007 May;12(2):229-52. | |||||
| REF 36 | ClinicalTrials.gov (NCT03577028) Study of HPN424 in Patients With Advanced Prostate Cancer. U.S. National Institutes of Health. | |||||
| REF 37 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800026421) | |||||
| REF 38 | ClinicalTrials.gov (NCT03926013) A Study of JNJ-63898081 in Participants With Advanced Stage Solid Tumors. U.S. National Institutes of Health. | |||||
| REF 39 | ClinicalTrials.gov (NCT03030885) A Phase 1, Open-Label, Dose Ascending Study to Evaluate the Safety and Tolerability of the Therapeutic Radiopharmaceutical 131I-MIP-1095 for the Treatment of Metastatic Castration-Resistant Prostate Cancer (mCRPC). U.S.National Institutes of Health. | |||||
| REF 40 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031326) | |||||
| REF 41 | Clinical pipeline report, company report or official report of Tmunity. | |||||
| REF 42 | Clinical pipeline report, company report or official report of Alphavax. | |||||
| REF 43 | J Clin Oncol 33, 2015 (suppl; abstr e13527) | |||||
| REF 44 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800012200) | |||||
| REF 45 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800015769) | |||||
| REF 46 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800026363) | |||||
| REF 47 | [177Lu-PSMA-617 therapy, dosimetry and follow-up in patients with metastatic castration-resistant prostate cancer]. Nuklearmedizin. 2016 Jun 28;55(3):123-8. | |||||
| REF 48 | Review of 177Lu-PSMA-617 in Patients With Metastatic Castration-Resistant Prostate Cancer. Cureus. 2020 Jun 30;12(6):e8921. | |||||
| REF 49 | 99mTc-labeled small-molecule inhibitors of prostate-specific membrane antigen for molecular imaging of prostate cancer. J Nucl Med. 2013 Aug;54(8):1369-76. | |||||
| REF 50 | Clinical pipeline report, company report or official report of Atlab pharma. | |||||
| REF 51 | National Cancer Institute Drug Dictionary (drug id 666090). | |||||
| REF 52 | Indium 111-labeled J591 anti-PSMA antibody for vascular targeted imaging in progressive solid tumors. EJNMMI Res. 2015 Apr 29;5:28. | |||||
| REF 53 | National Cancer Institute Drug Dictionary (drug name Lu-177-PSMA-R2). | |||||
| REF 54 | Radiopharmaceutical therapy in cancer: clinical advances and challenges. Nat Rev Drug Discov. 2020 Sep;19(9):589-608. | |||||
| REF 55 | Clinical pipeline report, company report or official report of Clarity Pharmaceuticals | |||||
| REF 56 | The PSMA-targeting Half-life Extended BiTE Therapy AMG 160 has Potent Antitumor Activity in Preclinical Models of Metastatic Castration-resistant Prostate Cancer. Clin Cancer Res. 2021 May 15;27(10):2928-2937. | |||||
| REF 57 | Clinical pipeline report, company report or official report of Lava Therapeutics | |||||
| REF 58 | Phase I trial of the prostate-specific membrane antigen-directed immunoconjugate MLN2704 in patients with progressive metastatic castration-resistant prostate cancer. J Clin Oncol. 2008 May 1;26(13):2147-54. | |||||
| REF 59 | Clinical pipeline report, company report or official report of Regeneron Pharmaceuticals. | |||||
| REF 60 | Clinical pipeline report, company report or official report of Cancer Targeted Technologies. | |||||
| REF 61 | Novel agents and clinical trials in castration-resistant prostate cancer: latest updates from 2023 ASCO-GU Cancers Symposium. Exp Hematol Oncol. 2023 Aug 1;12(1):68. | |||||
| REF 62 | (225)Ac-PSMA-617 for Therapy of Prostate Cancer. Semin Nucl Med. 2020 Mar;50(2):133-140. | |||||
| REF 63 | Darolutamide Potentiates the Antitumor Efficacy of a PSMA-targeted Thorium-227 Conjugate by a Dual Mode of Action in Prostate Cancer Models. Clin Cancer Res. 2021 May 25. | |||||
| REF 64 | Clinical pipeline report, company report or official report of Amgen. | |||||
| REF 65 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 66 | Antitumor activities of PSMA CD3 diabodies by redirected T-cell lysis of prostate cancer cells. Immunotherapy. 2013 Jan;5(1):27-38. | |||||
| REF 67 | Preclinical evaluation of BAY 1075553, a novel (18)F-labelled inhibitor of prostate-specific membrane antigen for PET imaging of prostate cancer. Eur J Nucl Med Mol Imaging. 2014 Jan;41(1):89-101. | |||||
| REF 68 | Clinical pipeline report, company report or official report of AbbVie. | |||||
| REF 69 | 177 Lu-Labeled Phosphoramidate-Based PSMA Inhibitors: The Effect of an Albumin Binder on Biodistribution and Therapeutic Efficacy in Prostate Tumor-Bearing Mice. Theranostics. 2017 Apr 27;7(7):1928-1939. | |||||
| REF 70 | Emerging drugs in neuropathic pain. Expert Opin Emerg Drugs. 2007 Mar;12(1):113-26. | |||||
| REF 71 | Clinical pipeline report, company report or official report of Harpoon Therapeutics. | |||||
| REF 72 | 123I-MIP-1072, a small-molecule inhibitor of prostate-specific membrane antigen, is effective at monitoring tumor response to taxane therapy. J Nucl Med. 2011 Jul;52(7):1087-93. | |||||
| REF 73 | Clinical pipeline report, company report or official report of Genmab. | |||||
| REF 74 | Radiation dosimetry and first therapy results with a (124)I/ (131)I-labeled small molecule (MIP-1095) targeting PSMA for prostate cancer therapy. Eur J Nucl Med Mol Imaging. 2014 Jul;41(7):1280-92. | |||||
| REF 75 | 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: 1606). | |||||
| REF 76 | Prostate-specific membrane antigen targeted imaging and therapy of prostate cancer using a PSMA inhibitor as a homing ligand. Mol Pharm. 2009 May-Jun;6(3):780-9. | |||||
| REF 77 | A phase I dose escalation trial of vaccine replicon particles (VRP) expressing prostate-specific membrane antigen (PSMA) in subjects with prostate cancer. Vaccine. 2013 Jan 30;31(6):943-9. | |||||
| REF 78 | Nanoparticles for Improving Cancer Diagnosis. Mater Sci Eng R Rep. 2013 March; 74(3): 35-69. | |||||
| REF 79 | Irx4 identifies a chamber-specific cell population that contributes to ventricular myocardium development. Dev Dyn. 2014 Mar;243(3):381-92. | |||||
| REF 80 | Structural optimization of thiol-based inhibitors of glutamate carboxypeptidase II by modification of the P1' side chain. J Med Chem. 2006 May 18;49(10):2876-85. | |||||
| REF 81 | Synthesis and biological evaluation of hydroxamate-Based inhibitors of glutamate carboxypeptidase II. Bioorg Med Chem Lett. 2003 Jul 7;13(13):2097-100. | |||||
| REF 82 | Synthesis and biological evaluation of thiol-based inhibitors of glutamate carboxypeptidase II: discovery of an orally active GCP II inhibitor. J Med Chem. 2003 May 8;46(10):1989-96. | |||||
| REF 83 | Selective inhibition of NAALADase, which converts NAAG to glutamate, reduces ischemic brain injury. Nat Med. 1999 Dec;5(12):1396-402. | |||||
| REF 84 | Design and synthesis of a siderophore conjugate as a potent PSMA inhibitor and potential diagnostic agent for prostate cancer. Bioorg Med Chem. 2008 Feb 15;16(4):1648-57. | |||||
| REF 85 | Synthesis of urea-based inhibitors as active site probes of glutamate carboxypeptidase II: efficacy as analgesic agents. J Med Chem. 2004 Mar 25;47(7):1729-38. | |||||
| REF 86 | Structural insight into the pharmacophore pocket of human glutamate carboxypeptidase II. J Med Chem. 2007 Jul 12;50(14):3267-73. | |||||
| REF 87 | Structural and biochemical characterization of the folyl-poly-Gamma-l-glutamate hydrolyzing activity of human glutamate carboxypeptidase II. FEBS J. 2014 Jul;281(14):3228-42. | |||||
| REF 88 | Glutamate Carboxypeptidase II | |||||
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