Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTZL0OI)

• DTT Name: Methionine aminopeptidase 2 (METAP2)
• Synonyms: Peptidase M 2; P67eIF2; P67; MetAP 2; METAP2; Initiation factor 2 associated 67 kDa glycoprotein; (MetAP)-2
• Gene Name: METAP2
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Peptidase
• UniProt ID: MAP2_HUMAN
• TTD ID: T75596
• EC Number: EC 3.4.11.18
• Sequence:
  MAGVEEVAASGSHLNGDLDPDDREEGAASTAEEAAKKKRRKKKKSKGPSAAGEQEPDKES
  GASVDEVARQLERSALEDKERDEDDEDGDGDGDGATGKKKKKKKKKRGPKVQTDPPSVPI
  CDLYPNGVFPKGQECEYPPTQDGRTAAWRTTSEEKKALDQASEEIWNDFREAAEAHRQVR
  KYVMSWIKPGMTMIEICEKLEDCSRKLIKENGLNAGLAFPTGCSLNNCAAHYTPNAGDTT
  VLQYDDICKIDFGTHISGRIIDCAFTVTFNPKYDTLLKAVKDATNTGIKCAGIDVRLCDV
  GEAIQEVMESYEVEIDGKTYQVKPIRNLNGHSIGQYRIHAGKTVPIVKGGEATRMEEGEV
  YAIETFGSTGKGVVHDDMECSHYMKNFDVGHVPIRLPRTKHLLNVINENFGTLAFCRRWL
  DRLGESKYLMALKNLCDLGIVDPYPPLCDIKGSYTAQFEHTILLRPTCKEVVSRGDDY
• 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).
• Reactome Pathway: Inactivation, recovery and regulation of the phototransduction cascade (R-HSA-2514859)
• BioCyc Pathway: MetaCyc:HS03371-MON

Molecular Interaction Atlas (MIA) of This DTT

6 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Beloranib	DM71CK8	Solid tumour/cancer	2A00-2F9Z	Phase 3	[1]
D-Methionine	DMMKGBP	N. A.	N. A.	Phase 3	[2]
ZGN-1061	DM9KB7A	Type 2 diabetes	5A11	Phase 2	[3]
M8891	DMZ9NVP	Solid tumour/cancer	2A00-2F9Z	Phase 1	[4]
PPI-2458	DMSAQBC	Autoimmune diabetes	5A10	Phase 1	[5]
SDX-7320	DMU0Q6L	Solid tumour/cancer	2A00-2F9Z	Phase 1	[4]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
TNP-470	DMT0QK8	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 2	[6]

24 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
2-(4-fluorophenylsulfonamido)-1-naphthoic acid	DM0CDRP	Discovery agent	N.A.	Investigative	[7]
2-(phenylsulfonamido)-1-naphthoic acid	DMFBTM2	Discovery agent	N.A.	Investigative	[7]
2-(phenylsulfonamido)-5-propylbenzoic acid	DMDGAHO	Discovery agent	N.A.	Investigative	[7]
2-(pyridin-2-yl)-1H-benzo[d]imidazol-5-amine	DMST2LX	Discovery agent	N.A.	Investigative	[8]
2-(pyridin-2-yl)-1H-benzo[d]imidazole	DMRUTDY	Discovery agent	N.A.	Investigative	[8]
2-(pyridin-2-yl)-1H-imidazo[4,5-c]pyridine	DMHFGMQ	Discovery agent	N.A.	Investigative	[8]
2-(thiazol-4-yl)-1H-benzo[d]imidazol-5-amine	DMH4IRP	Discovery agent	N.A.	Investigative	[8]
2-Methyl-2-Propanol	DMHM5GJ	Discovery agent	N.A.	Investigative	[2]
3,5,6,8-Tetramethyl-N-Methyl Phenanthrolinium	DMAU80W	Discovery agent	N.A.	Investigative	[2]
3,5-dimethyl-2-(phenylsulfonamido)benzoic acid	DMAQ6OM	Discovery agent	N.A.	Investigative	[7]
3-anilino-5-benzylthio-1,2,4-triazole	DM3VYNJ	Discovery agent	N.A.	Investigative	[9]
5-bromo-2-(4-chlorophenylsulfonamido)benzoic acid	DM4WVSB	Discovery agent	N.A.	Investigative	[7]
5-butyl-2-(phenylsulfonamido)benzoic acid	DMI7DSM	Discovery agent	N.A.	Investigative	[7]
5-chloro-2-(pyridin-2-yl)-1H-benzo[d]imidazole	DMJBHR9	Discovery agent	N.A.	Investigative	[8]
5-ethyl-2-(phenylsulfonamido)benzoic acid	DM0E9O1	Discovery agent	N.A.	Investigative	[7]
5-fluoro-2-(pyridin-2-yl)-1H-benzo[d]imidazole	DMEA8WP	Discovery agent	N.A.	Investigative	[8]
5-methyl-2-(phenylsulfonamido)benzoic acid	DMC10HG	Discovery agent	N.A.	Investigative	[10]
5-methyl-2-(pyridin-2-yl)-1H-benzo[d]imidazole	DMAR4ZF	Discovery agent	N.A.	Investigative	[8]
5-p-Tolyl-1H-[1,2,3]triazole	DM2W0AD	Discovery agent	N.A.	Investigative	[11]
A-357300	DMZHDWN	Discovery agent	N.A.	Investigative	[6]
Fumagillin	DMA3Y8C	Discovery agent	N.A.	Investigative	[12]
Ovalicin	DMM4CE7	Discovery agent	N.A.	Investigative	[2]
OXYQUINOLINE	DMZVS9Y	Discovery agent	N.A.	Investigative	[8]
XMT-1191	DM5TR49	Discovery agent	N.A.	Investigative	[13]

References

• [1] 2011 Pipeline of Zafgen.
• [2] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [3] The methionine aminopeptidase 2 inhibitor ZGN-1061 improves glucose control and weight in overweight and obese individuals with type 2 diabetes: A randomized, placebo-controlled trial. Diabetes Obes Metab. 2020 Jul;22(7):1215-1219.
• [4] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [5] Metabolites 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.
• [6] Tumor suppression by a rationally designed reversible inhibitor of methionine aminopeptidase-2. Cancer Res. 2003 Nov 15;63(22):7861-9.
• [7] Development of sulfonamide compounds as potent methionine aminopeptidase type II inhibitors with antiproliferative properties. Bioorg Med Chem Lett. 2006 Jul 1;16(13):3574-7.
• [8] Subtype-selectivity of metal-dependent methionine aminopeptidase inhibitors, Bioorg. Med. Chem. Lett. 20(14):4038-4044 (2010).
• [9] Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore. J Med Chem. 2007 Aug 9;50(16):3777-85.
• [10] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [11] 4-Aryl-1,2,3-triazole: a novel template for a reversible methionine aminopeptidase 2 inhibitor, optimized to inhibit angiogenesis in vivo. J Med Chem. 2005 Sep 8;48(18):5644-7.
• [12] Homology 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.
• [13] 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: 1573).