General Information of Drug Therapeutic Target (DTT) (ID: TTP18AY)

DTT Name Carboxypeptidase B2 (CPB2)
Synonyms Thrombin-activable fibrinolysis inhibitor; TAFI; Plasma carboxypeptidase B; Carboxypeptidase U; CPU; CPB2
Gene Name CPB2
DTT Type
Clinical trial target
[1]
BioChemical Class
Peptidase
UniProt ID
CBPB2_HUMAN
TTD ID
T98022
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
EC 3.4.17.20
Sequence
MKLCSLAVLVPIVLFCEQHVFAFQSGQVLAALPRTSRQVQVLQNLTTTYEIVLWQPVTAD
LIVKKKQVHFFVNASDVDNVKAHLNVSGIPCSVLLADVEDLIQQQISNDTVSPRASASYY
EQYHSLNEIYSWIEFITERHPDMLTKIHIGSSFEKYPLYVLKVSGKEQAAKNAIWIDCGI
HAREWISPAFCLWFIGHITQFYGIIGQYTNLLRLVDFYVMPVVNVDGYDYSWKKNRMWRK
NRSFYANNHCIGTDLNRNFASKHWCEEGASSSSCSETYCGLYPESEPEVKAVASFLRRNI
NQIKAYISMHSYSQHIVFPYSYTRSKSKDHEELSLVASEAVRAIEKISKNTRYTHGHGSE
TLYLAPGGGDDWIYDLGIKYSFTIELRDTGTYGFLLPERYIKPTCREAFAAVSKIAWHVI
RNV
Function
Cleaves C-terminal arginine or lysine residues from biologically active peptides such as kinins or anaphylatoxins in the circulation thereby regulating their activities. Down- regulates fibrinolysis by removing C-terminal lysine residues from fibrin that has already been partially degraded by plasmin.
KEGG Pathway
Complement and coagulation cascades (hsa04610 )
Pancreatic secretion (hsa04972 )
Protein digestion and absorption (hsa04974 )
Reactome Pathway
Metabolism of Angiotensinogen to Angiotensins (R-HSA-2022377 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
4 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
DS-1040 DMXCN37 Ischemic stroke 8B11.5Z Phase 1 [2]
SAR-104772 DMQ9ZY0 Cerebrovascular ischaemia 8B1Z Phase 1 [3]
SAR-126119 DMKHM7O Cerebrovascular ischaemia 8B1Z Phase 1 [1]
UK-396082 DMFYKDX Thrombosis DB61-GB90 Phase 1 [4]
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1 Discontinued Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
AZD-9684 DMHA5ME Thrombosis DB61-GB90 Discontinued in Phase 2 [5]
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13 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
(+/-)-5-amino-2-(mercaptomethyl)pentanoic acid DMSNWA6 Discovery agent N.A. Investigative [6]
2-(3-aminophenyl)-3-mercaptopropanoic acid DMQB9SC Discovery agent N.A. Investigative [7]
2-(3-guanidinophenyl)-3-mercaptopropanoic acid DMZX2GE Discovery agent N.A. Investigative [7]
2-(4-benzoylpiperidine-1-carbonyl)benzoic acid DMGMZV9 Discovery agent N.A. Investigative [8]
3-mercapto-2-(piperidin-3-yl)propanoic acid DMPJBNC Discovery agent N.A. Investigative [7]
3-mercapto-2-(piperidin-4-yl)propanoic acid DMYQG7A Discovery agent N.A. Investigative [7]
6-Amino-2-(1H-imidazol-4-yl)-hexanoic acid DMMUE05 Discovery agent N.A. Investigative [9]
DL-benzylsuccinic acid DMHI9ZJ Discovery agent N.A. Investigative [8]
DL-guanidinoethylmercaptosuccinic acid DMM1GXI Discovery agent N.A. Investigative [8]
MN-462 DM1XY5F Thrombosis DB61-GB90 Investigative [10]
PMID14640538C3 DMR2L6X Discovery agent N.A. Investigative [11]
PMID19954973C4 DMDYZE5 Discovery agent N.A. Investigative [4]
SQ-24798 DMW7Y9L Discovery agent N.A. Investigative [7]
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⏷ Show the Full List of 13 Investigative Drug(s)

References

1 TAFIa inhibitors in the treatment of thrombosis. Curr Opin Drug Discov Devel. 2008 Jul;11(4):480-6.
2 Clinical pipeline report, company report or official report of Daiichi Sankyo.
3 Carboxypeptidase U (TAFIa): a new drug target for fibrinolytic therapy . Journal of Thrombosis and Haemostasis Volume 7, Issue 12, pages 1962-1971, December 2009.
4 Oxygenated analogues of UK-396082 as inhibitors of activated thrombin activatable fibrinolysis inhibitor. Bioorg Med Chem Lett. 2010 Jan 1;20(1):92-6.
5 Clinical pipeline report, company report or official report of AstraZeneca.
6 Discovery of potent & selective inhibitors of activated thrombin-activatable fibrinolysis inhibitor for the treatment of thrombosis. J Med Chem. 2007 Nov 29;50(24):6095-103.
7 3-Mercaptopropionic acids as efficacious inhibitors of activated thrombin activatable fibrinolysis inhibitor (TAFIa). Bioorg Med Chem Lett. 2007 Mar 1;17(5):1349-54.
8 A new type of five-membered heterocyclic inhibitors of basic metallocarboxypeptidases. Eur J Med Chem. 2009 Aug;44(8):3266-71.
9 Imidazole acetic acid TAFIa inhibitors: SAR studies centered around the basic P(1)(') group. Bioorg Med Chem Lett. 2004 May 3;14(9):2141-5.
10 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: 1594).
11 Synthesis and evaluation of imidazole acetic acid inhibitors of activated thrombin-activatable fibrinolysis inhibitor as novel antithrombotics. J Med Chem. 2003 Dec 4;46(25):5294-7.