Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT9G4N0)

• DTT Name: Glutamate carboxypeptidase II (GCPII)
• 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
• Gene Name: FOLH1
• DTT Type: Successful target; [1]
• BioChemical Class: Peptidase
• UniProt ID: FOLH1_HUMAN
• TTD ID: T97071
• EC Number: EC 3.4.17.21
• Sequence:
  MWNLLHETDSAVATARRPRWLCAGALVLAGGFFLLGFLFGWFIKSSNEATNITPKHNMKA
  FLDELKAENIKKFLYNFTQIPHLAGTEQNFQLAKQIQSQWKEFGLDSVELAHYDVLLSYP
  NKTHPNYISIINEDGNEIFNTSLFEPPPPGYENVSDIVPPFSAFSPQGMPEGDLVYVNYA
  RTEDFFKLERDMKINCSGKIVIARYGKVFRGNKVKNAQLAGAKGVILYSDPADYFAPGVK
  SYPDGWNLPGGGVQRGNILNLNGAGDPLTPGYPANEYAYRRGIAEAVGLPSIPVHPIGYY
  DAQKLLEKMGGSAPPDSSWRGSLKVPYNVGPGFTGNFSTQKVKMHIHSTNEVTRIYNVIG
  TLRGAVEPDRYVILGGHRDSWVFGGIDPQSGAAVVHEIVRSFGTLKKEGWRPRRTILFAS
  WDAEEFGLLGSTEWAEENSRLLQERGVAYINADSSIEGNYTLRVDCTPLMYSLVHNLTKE
  LKSPDEGFEGKSLYESWTKKSPSPEFSGMPRISKLGSGNDFEVFFQRLGIASGRARYTKN
  WETNKFSGYPLYHSVYETYELVEKFYDPMFKYHLTVAQVRGGMVFELANSIVLPFDCRDY
  AVVLRKYADKIYSISMKHPQEMKTYSVSFDSLFSAVKNFTEIASKFSERLQDFDKSNPIV
  LRMMNDQLMFLERAFIDPLGLPDRPFYRHVIYAPSSHNKYAGESFPGIYDALFDIESKVD
  PSKAWGEVKRQIYVAAFTVQAAAETLSEVA
• 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.
• KEGG Pathway:
  Alanine, aspartate and glutamate metabolism (hsa00250)
  Metabolic pathways (hsa01100)
  Vitamin digestion and absorption (hsa04977)
• Reactome Pathway: Amino acid synthesis and interconversion (transamination) (R-HSA-70614)

Molecular Interaction Atlas (MIA) of This DTT

3 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Capromab	DMHERIJ	Prostate cancer	2C82.0	Approved	[1]
Lutetium Lu-177 vipivotide tetraxetan	DMQ0IZ6	Prostate cancer	2C82.0	Approved	[2]
PSMA-11 Ga-68	DMWLTU2	Diagnostic imaging	N.A.	Approved	[3]

40 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
177-Lu-PSMA-617	DMX178V	Prostate cancer	2C82.0	Phase 3	[4]
BAY 2315497	DMUHH2G	Prostate cancer	2C82.0	Phase 3	[5]
99mTc-MIP-1404	DML4GU1	Prostate cancer	2C82.0	Phase 2	[6]
ATL101	DMYAQV2	Influenza virus infection	1E30-1E32	Phase 2	[7]
G-202	DMQR9I8	Adenocarcinoma	2D40	Phase 2	[8]
J 591 Lu-177	DM9XKJU	Prostate cancer	2C82.0	Phase 2	[9]
MLN-591RL	DMJHVZC	Prostate cancer	2C82.0	Phase 2	[10]
177-Lu-PSMA-R2	DMF4AOE	Prostate cancer	2C82.0	Phase 1/2	[11]
177Lu-labelled PSMA-R2	DMWPD7N	Prostate cancer	2C82.0	Phase 1/2	[12]
4SCAR-PSMA	DMM8J5W	Bladder cancer	2C94	Phase 1/2	[13]
64Cu-SAR-bisPSMA	DMGUHFN	Prostate cancer	2C82.0	Phase 1/2	[14]
67Cu-SAR-bisPSMA	DMMYR39	Prostate cancer	2C82.0	Phase 1/2	[14]
Acapatamab	DMTAI2F	Prostate cancer	2C82.0	Phase 1/2	[15]
CAR-T cells targeting PSMA	DMW340V	Cervical cancer	2C77.0	Phase 1/2	[16]
LAVA-1207	DMQIZ8V	Prostate cancer	2C82.0	Phase 1/2	[17]
MLN-2704	DMGC96P	Prostate cancer	2C82.0	Phase 1/2	[18]
REGN4336	DMAKSZW	Prostate cancer	2C82.0	Phase 1/2	[19]
REGN5678	DM0Y6WU	Prostate cancer	2C82.0	Phase 1/2	[20]
177Lu-labelled CTT-1403	DMM2V74	Prostate cancer	2C82.0	Phase 1	[21]
225Ac-J591	DMVHFE1	Prostate cancer	2C82.0	Phase 1	[22]
225Ac-PSMA-617	DMG77MF	Aggressive cancer	2A00-2F9Z	Phase 1	[23]
227Th-labelled PSMA-TTC	DM7L45S	Prostate cancer	2C82.0	Phase 1	[24]
99mTc-MIP-1405	DMJB6E2	Prostate cancer	2C82.0	Phase 1	[6]
AMG 160	DMM0HNF	Non-small-cell lung cancer	2C25	Phase 1	[25]
AMG 340	DM3VRX6	Prostate cancer	2C82.0	Phase 1	[26]
APVO414	DMXDMH5	Prostate cancer	2C82.0	Phase 1	[27]
Autologous T-cell therapy	DMOAET3	Prostate cancer	2C82.0	Phase 1	[28]
BAY-1075553	DM8U3Q2	Prostate cancer	2C82.0	Phase 1	[29]
CCW702	DMPTYE6	Prostate cancer	2C82.0	Phase 1	[30]
CTT1403	DMAV86R	Prostate cancer	2C82.0	Phase 1	[31]
GPI-16072	DM0ZQ48	Neuropathic pain	8E43.0	Phase 1	[32]
HPN424	DMLZDVR	Prostate cancer	2C82.0	Phase 1	[33]
Iofolastat I-124	DMNBPKS	Prostate cancer	2C82.0	Phase 1	[34]
JNJ-63898081	DMJFK6X	Solid tumour/cancer	2A00-2F9Z	Phase 1	[35]
MIP-1095	DMELSIU	Prostate cancer	2C82.0	Phase 1	[36]
MT-112	DMT0EBU	Solid tumour/cancer	2A00-2F9Z	Phase 1	[37]
PSMA CAR-T cell therapy	DM8Y1M9	Prostate cancer	2C82.0	Phase 1	[38]
PSMA subunit vaccine	DMRHQTU	Prostate cancer	2C82.0	Phase 1	[37]
PSMA-targeted tubulysin B conjugates	DMOYX6W	Prostate cancer	2C82.0	Phase 1	[39]
PSMA-VRP	DM03O8T	Prostate cancer	2C82.0	Phase 1	[40]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
MDX-070	DM9ZEGT	Prostate cancer	2C82.0	Discontinued in Phase 2	[41]

1 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
IRX-4	DMMUVAF	Prostate cancer	2C82.0	Preclinical	[42]

39 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
2-(2-carboxy-5-mercaptopentyl)benzoic acid	DMEGY0T	Discovery agent	N.A.	Investigative	[43]
2-(2-carboxy-7-mercaptoheptyl)benzoic acid	DMR98ML	Discovery agent	N.A.	Investigative	[43]
2-(2-Hydroxycarbamoyl-ethyl)-pentanedioic acid	DMMEL39	Discovery agent	N.A.	Investigative	[44]
2-(2-Mercapto-ethyl)-pentanedioic acid	DMGELY0	Discovery agent	N.A.	Investigative	[45]
2-(2-Phosphonooxy-ethyl)-pentanedioic acid	DMQM6IA	Discovery agent	N.A.	Investigative	[45]
2-(3-carbamoylbenzyl)-5-mercaptopentanoic acid	DMHXVNZ	Discovery agent	N.A.	Investigative	[43]
2-(3-carboxybenzyl)succinic acid	DMI6AZ5	Discovery agent	N.A.	Investigative	[43]
2-(3-cyanobenzyl)-5-mercaptopentanoic acid	DMVB5U0	Discovery agent	N.A.	Investigative	[43]
2-(3-Hydroxycarbamoyl-propyl)-pentanedioic acid	DMFVITM	Discovery agent	N.A.	Investigative	[44]
2-(3-Mercapto-propyl)-pentanedioic acid	DMMDNA8	Discovery agent	N.A.	Investigative	[45]
2-(3-Methylsulfanyl-propyl)-pentanedioic acid	DM4D1UT	Discovery agent	N.A.	Investigative	[45]
2-(4-Mercapto-butyl)-pentanedioic acid	DMXPJF3	Discovery agent	N.A.	Investigative	[45]
2-(5-Mercapto-pentyl)-pentanedioic acid	DM0P6A3	Discovery agent	N.A.	Investigative	[45]
2-benzyl-5-mercaptopentanoic acid	DM3I7EL	Discovery agent	N.A.	Investigative	[43]
2-Hydroxycarbamoyl-pentanedioic acid	DM412RI	Discovery agent	N.A.	Investigative	[44]
2-Hydroxycarbamoylmethyl-pentanedioic acid	DMA8DZT	Discovery agent	N.A.	Investigative	[44]
2-Mercapto-pentanedioic acid	DMRVBCI	Discovery agent	N.A.	Investigative	[45]
2-Mercaptomethyl-pentanedioic acid	DMHK25N	Discovery agent	N.A.	Investigative	[45]
2-Phosphonooxy-pentanedioic acid	DMM05AO	Discovery agent	N.A.	Investigative	[45]
2-PMPA	DM27GZC	Discovery agent	N.A.	Investigative	[46]
3-(1-carboxy-4-mercaptobutoxy)benzoic acid	DMHPYWM	Discovery agent	N.A.	Investigative	[43]
3-(2-carbamoyl-5-mercaptopentyl)benzoic acid	DMNOKR3	Discovery agent	N.A.	Investigative	[43]
3-(2-carboxy-3-mercaptopropyl)benzoic acid	DM67B8S	Discovery agent	N.A.	Investigative	[43]
3-(2-carboxy-3-phosphonopropyl)benzoic acid	DMG5R0N	Discovery agent	N.A.	Investigative	[43]
3-(2-carboxy-4-mercaptobutyl)benzoic acid	DM6HPYN	Discovery agent	N.A.	Investigative	[43]
3-(2-carboxy-5-mercaptopentyl)benzoic acid	DM6H52B	Discovery agent	N.A.	Investigative	[43]
3-(2-carboxy-6-mercaptohexyl)benzoic acid	DM870W1	Discovery agent	N.A.	Investigative	[43]
3-[(1-carboxy-4-mercaptobutyl)thio]benzoic acid	DMLSET4	Discovery agent	N.A.	Investigative	[43]
4-(2-carboxy-5-mercaptopentyl)benzoic acid	DM5L4WP	Discovery agent	N.A.	Investigative	[43]
5-Mercapto-pentanoic acid	DM7YGJO	Discovery agent	N.A.	Investigative	[45]
99mTc-EC-0652	DMAGTL1	Prostate cancer	2C82.0	Investigative	[37]
99mTc-MIP-1340	DMQOFX2	Prostate cancer	2C82.0	Investigative	[37]
CTT-54	DMQ5JX8	Solid tumour/cancer	2A00-2F9Z	Investigative	[37]
J591-Ac-225	DMXC319	Prostate cancer	2C82.0	Investigative	[37]
MDX-1147	DM9ZTX4	Prostate cancer	2C82.0	Investigative	[37]
MIP-1375	DM0J38I	Prostate cancer	2C82.0	Investigative	[37]
PGI-02749	DMTVY6K	Brain injury	NA07.Z	Investigative	[37]
PMID15027864C8d	DMOQ8PF	Discovery agent	N.A.	Investigative	[47]
[3H]quisqualate	DMDQBTX	Discovery agent	N.A.	Investigative	[48]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Prostate cancer	2C82	Prostate	1.40E-09	2.08	2.21

The Drug-Metabolizing Enzyme (DME) Role of This DTT

• DTT DME Name: Glutamate carboxypeptidase II (FOLH1) DME Info
• Gene Name: FOLH1

1 Approved Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[49]

References

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