Target Information

Target General Infomation
Target ID
T82739
Former ID
TTDC00013
Target Name
Plasma kallikrein
Gene Name
KLKB1
Synonyms
Fletcher factor; KLK3; Kininogenin; Plasma kallikrein heavy chain; Plasma kallikrein light chain; Plasma prekallikrein; KLKB1
Target Type
Successful
Disease Retinal venous occlusion [ICD10: H34.8]
Function
The enzyme cleaves Lys-Arg and Arg-Ser bonds. It activates, in a reciprocal reaction, factor XII after its binding to a negatively charged surface. It also releases bradykinin from HMW kininogen and may also playa role in the renin-angiotensin system by converting prorenin into renin.
BioChemical Class
Peptidase
Target Validation
T82739
UniProt ID
P03952
EC Number
EC 3.4.21.34
Sequence
MILFKQATYFISLFATVSCGCLTQLYENAFFRGGDVASMYTPNAQYCQMRCTFHPRCLLF
SFLPASSINDMEKRFGCFLKDSVTGTLPKVHRTGAVSGHSLKQCGHQISACHRDIYKGVD
MRGVNFNVSKVSSVEECQKRCTNNIRCQFFSYATQTFHKAEYRNNCLLKYSPGGTPTAIK
VLSNVESGFSLKPCALSEIGCHMNIFQHLAFSDVDVARVLTPDAFVCRTICTYHPNCLFF
TFYTNVWKIESQRNVCLLKTSESGTPSSSTPQENTISGYSLLTCKRTLPEPCHSKIYPGV
DFGGEELNVTFVKGVNVCQETCTKMIRCQFFTYSLLPEDCKEEKCKCFLRLSMDGSPTRI
AYGTQGSSGYSLRLCNTGDNSVCTTKTSTRIVGGTNSSWGEWPWQVSLQVKLTAQRHLCG
GSLIGHQWVLTAAHCFDGLPLQDVWRIYSGILNLSDITKDTPFSQIKEIIIHQNYKVSEG
NHDIALIKLQAPLNYTEFQKPICLPSKGDTSTIYTNCWVTGWGFSKEKGEIQNILQKVNI
PLVTNEECQKRYQDYKITQRMVCAGYKEGGKDACKGDSGGPLVCKHNGMWRLVGITSWGE
GCARREQPGVYTKVAEYMDWILEKTQSSDGKAQMQSPA
Drugs and Mode of Action
Drug(s) Ecallantide Drug Info Approved Retinal venous occlusion [522774], [541991]
Inhibitor (3,4-dichlorophenyl)(1H-pyrazol-1-yl)methanone Drug Info [529037]
(3-nitro-1H-pyrazol-1-yl)(p-tolyl)methanone Drug Info [529037]
(3-nitro-1H-pyrazol-1-yl)(phenyl)methanone Drug Info [529037]
(4-bromo-1H-pyrazol-1-yl)(p-tolyl)methanone Drug Info [529037]
1-benzoyl-N-phenyl-1H-pyrazole-3-carboxamide Drug Info [529037]
D-Pro-Phe-Arg chloromethyl ketone Drug Info [529454]
Ecallantide Drug Info [536771]
ZK-810388 Drug Info [528872]
ZK-814048 Drug Info [528872]
Pathways
KEGG Pathway Complement and coagulation cascades
NetPath Pathway AndrogenReceptor Signaling Pathway
PANTHER Pathway Blood coagulation
PathWhiz Pathway Coagulation
Reactome Intrinsic Pathway of Fibrin Clot Formation
Activation of Matrix Metalloproteinases
WikiPathways Complement and Coagulation Cascades
Human Complement System
Blood Clotting Cascade
Formation of Fibrin Clot (Clotting Cascade)
References
Ref 522774ClinicalTrials.gov (NCT00969293) Study to Assess the Safety and Tolerability of a Single Administration of FOV2302 (Ecallantide) in Patients With Macular Edema Associated With Central Retinal Vein Occlusion. U.S. National Institutes of Health.
Ref 541991(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: 6955).
Ref 528872J Med Chem. 2007 Jun 28;50(13):2967-80. Epub 2007 May 31.Thiophene-anthranilamides as highly potent and orally available factor Xa inhibitors.
Ref 529037J Med Chem. 2007 Oct 4;50(20):4928-38. Epub 2007 Sep 12.N-benzoylpyrazoles are novel small-molecule inhibitors of human neutrophil elastase.
Ref 529454J Med Chem. 2008 Jun 12;51(11):3077-80. Epub 2008 May 7.Novel 3-carboxamide-coumarins as potent and selective FXIIa inhibitors.
Ref 536771Ecallantide (DX-88), a plasma kallikrein inhibitor for the treatment of hereditary angioedema and the prevention of blood loss in on-pump cardiothoracic surgery. Expert Opin Biol Ther. 2008 Aug;8(8):1187-99.

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