Target Information

Target General Infomation
Target ID
T75596
Former ID
TTDR00721
Target Name
Methionine aminopeptidase 2
Gene Name
METAP2
Synonyms
(MetAP)-2; Initiation factor 2 associated 67 kDa glycoprotein; MetAP 2; P67; P67eIF2; Peptidase M 2; METAP2
Target Type
Clinical Trial
Disease Autoimmune diabetes [ICD10: E08-E13]
Obesity [ICD9: 278; ICD10: E66]
Solid tumours [ICD9: 140-199, 210-229; ICD10: C00-D48]
Function
Cotranslationally removes the N-terminal methionine from nascent proteins. The N-terminal methionine is often cleaved when the second residue in the primary sequence is small and uncharged (Met-Ala-, Cys, Gly, Pro, Ser, Thr, or Val).
BioChemical Class
Peptidase
Target Validation
T75596
UniProt ID
P50579
EC Number
EC 3.4.11.18
Sequence
MAGVEEVAASGSHLNGDLDPDDREEGAASTAEEAAKKKRRKKKKSKGPSAAGEQEPDKES
GASVDEVARQLERSALEDKERDEDDEDGDGDGDGATGKKKKKKKKKRGPKVQTDPPSVPI
CDLYPNGVFPKGQECEYPPTQDGRTAAWRTTSEEKKALDQASEEIWNDFREAAEAHRQVR
KYVMSWIKPGMTMIEICEKLEDCSRKLIKENGLNAGLAFPTGCSLNNCAAHYTPNAGDTT
VLQYDDICKIDFGTHISGRIIDCAFTVTFNPKYDTLLKAVKDATNTGIKCAGIDVRLCDV
GEAIQEVMESYEVEIDGKTYQVKPIRNLNGHSIGQYRIHAGKTVPIVKGGEATRMEEGEV
YAIETFGSTGKGVVHDDMECSHYMKNFDVGHVPIRLPRTKHLLNVINENFGTLAFCRRWL
DRLGESKYLMALKNLCDLGIVDPYPPLCDIKGSYTAQFEHTILLRPTCKEVVSRGDDY
Structure
1B59; 1B6A; 1BN5; 1BOA; 1KQ0; 1KQ9; 1QZY; 1R58; 1R5G; 1R5H; 1YW7; 1YW8; 1YW9; 2ADU; 2EA2; 2EA4; 2GA2; 2OAZ; 3FM3; 3FMQ; 3FMR
Drugs and Mode of Action
Drug(s) Beloranib Drug Info Phase 3 Solid tumours [524814], [543139]
D-Methionine Drug Info Phase 3 Discovery agent [523457]
PPI-2458 Drug Info Phase 1 Autoimmune diabetes [521623]
ZGN-433 Drug Info Phase 1 Obesity [551785]
TNP-470 Drug Info Discontinued in Phase 2 Solid tumours [544934]
Inhibitor 2-(4-fluorophenylsulfonamido)-1-naphthoic acid Drug Info [528149]
2-(phenylsulfonamido)-1-naphthoic acid Drug Info [528149]
2-(phenylsulfonamido)-5-propylbenzoic acid Drug Info [528149]
2-(pyridin-2-yl)-1H-benzo[d]imidazol-5-amine Drug Info [551242]
2-(pyridin-2-yl)-1H-benzo[d]imidazole Drug Info [551242]
2-(pyridin-2-yl)-1H-imidazo[4,5-c]pyridine Drug Info [551242]
2-(thiazol-4-yl)-1H-benzo[d]imidazol-5-amine Drug Info [551242]
2-Methyl-2-Propanol Drug Info [551393]
3,5,6,8-Tetramethyl-N-Methyl Phenanthrolinium Drug Info [551393]
3,5-dimethyl-2-(phenylsulfonamido)benzoic acid Drug Info [528149]
3-anilino-5-benzylthio-1,2,4-triazole Drug Info [528951]
5-bromo-2-(4-chlorophenylsulfonamido)benzoic acid Drug Info [528149]
5-butyl-2-(phenylsulfonamido)benzoic acid Drug Info [528149]
5-chloro-2-(pyridin-2-yl)-1H-benzo[d]imidazole Drug Info [551242]
5-ethyl-2-(phenylsulfonamido)benzoic acid Drug Info [528149]
5-fluoro-2-(pyridin-2-yl)-1H-benzo[d]imidazole Drug Info [551242]
5-methyl-2-(phenylsulfonamido)benzoic acid Drug Info [528266]
5-methyl-2-(pyridin-2-yl)-1H-benzo[d]imidazole Drug Info [551242]
5-METHYL-2-[(PHENYLSULFONYL)AMINO]BENZOIC ACID Drug Info [551374]
5-p-Tolyl-1H-[1,2,3]triazole Drug Info [527712]
A-357300 Drug Info [535871]
Beloranib Drug Info [532701]
D-Methionine Drug Info [551393]
Ovalicin Drug Info [551393]
OXYQUINOLINE Drug Info [551242]
PPI-2458 Drug Info [532203]
TNP-470 Drug Info [535871]
XMT-1191 Drug Info [543441]
ZGN-433 Drug Info [551785]
Binder Fumagillin Drug Info [535781]
Pathways
Reactome Inactivation, recovery and regulation of the phototransduction cascade
References
Ref 521623ClinicalTrials.gov (NCT00100347) Safety/Tolerance Study of PPI-2458 in Subjects With Non-Hodgkin's Lymphoma and Solid Tumors. U.S. National Institutes of Health.
Ref 523457ClinicalTrials.gov (NCT01345474) Phase 3 Clinical Trial: D-Methionine to Reduce Noise-Induced Hearing Loss (NIHL). U.S. National Institutes of Health.
Ref 524814ClinicalTrials.gov (NCT02179151) Double-Blind, Placebo Controlled, Phase 3 Trial of ZGN-440 (Beloranib) in Obese Subjects With Prader-Willi Syndrome. U.S. National Institutes of Health.
Ref 543139(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: 8445).
Ref 544934Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001587)
Ref 5517852011 Pipeline of Zafgen.
Ref 527712J Med Chem. 2005 Sep 8;48(18):5644-7.4-Aryl-1,2,3-triazole: a novel template for a reversible methionine aminopeptidase 2 inhibitor, optimized to inhibit angiogenesis in vivo.
Ref 528149Bioorg Med Chem Lett. 2006 Jul 1;16(13):3574-7. Epub 2006 May 2.Development of sulfonamide compounds as potent methionine aminopeptidase type II inhibitors with antiproliferative properties.
Ref 528266J Med Chem. 2006 Jun 29;49(13):3832-49.Discovery and optimization of anthranilic acid sulfonamides as inhibitors of methionine aminopeptidase-2: a structural basis for the reduction of albumin binding.
Ref 528951J Med Chem. 2007 Aug 9;50(16):3777-85. Epub 2007 Jul 18.Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.
Ref 532203Metabolites of PPI-2458, a selective, irreversible inhibitor of methionine aminopeptidase-2: structure determination and in vivo activity. Drug Metab Dispos. 2013 Apr;41(4):814-26.
Ref 532701Inhibition of the methionine aminopeptidase 2 enzyme for the treatment of obesity. Diabetes Metab Syndr Obes. 2014 Feb 28;7:73-84.
Ref 535781Homology modeling and calculation of the cobalt cluster charges of the Encephazlitozoon cuniculi methionine aminopeptidase, a potential target for drug design. Biophys Chem. 2003 Aug 1;105(1):29-43.
Ref 535871Tumor suppression by a rationally designed reversible inhibitor of methionine aminopeptidase-2. Cancer Res. 2003 Nov 15;63(22):7861-9.
Ref 543441(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: 1573).
Ref 551242Subtype-selectivity of metal-dependent methionine aminopeptidase inhibitors, Bioorg. Med. Chem. Lett. 20(14):4038-4044 (2010).
Ref 551374The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
Ref 551393How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
Ref 5517852011 Pipeline of Zafgen.

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