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kallikrein B1

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 2379

Nomenclature: kallikrein B1

Family: S1: Chymotrypsin

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 638 4q35.2 KLKB1 kallikrein B1
Mouse - 638 8 25.17 cM Klkb1 kallikrein B, plasma 1
Rat - 638 16q11 Klkb1 kallikrein B1
Previous and Unofficial Names Click here for help
antigen, prostate specific | APS | Kal3 | kallikrein 3, plasma | Kalp1 | KALP15 | kininogenin | Klk3 | plasma kallikrein | kallikrein B, plasma (Fletcher factor) 1 | kallikrein B, plasma 1 | kallikrein B
Database Links Click here for help
Specialist databases
MEROPS S01.212 (Hs)
Other databases
Alphafold P03952 (Hs), P26262 (Mm), P14272 (Rn)
BRENDA 3.4.21.34
ChEMBL Target CHEMBL2000 (Hs), CHEMBL1250359 (Mm), CHEMBL4105792 (Rn)
Ensembl Gene ENSG00000164344 (Hs), ENSMUSG00000109764 (Mm), ENSRNOG00000014118 (Rn)
Entrez Gene 3818 (Hs), 16621 (Mm), 25048 (Rn)
Human Protein Atlas ENSG00000164344 (Hs)
KEGG Enzyme 3.4.21.34
KEGG Gene hsa:3818 (Hs), mmu:16621 (Mm), rno:25048 (Rn)
OMIM 229000 (Hs)
Orphanet ORPHA122872 (Hs)
Pharos P03952 (Hs)
RefSeq Nucleotide NM_000892 (Hs), NM_008455 (Mm), NM_012725 (Rn)
RefSeq Protein NP_000883 (Hs), NP_032481 (Mm), NP_036857 (Rn)
UniProtKB P03952 (Hs), P26262 (Mm), P14272 (Rn)
Wikipedia KLKB1 (Hs)
Enzyme Reaction Click here for help
EC Number: 3.4.21.34

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
compound 11 [PMID: 16413183] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 9.3 pKi 7
⤷ pKi 9.3 (Ki 5x10-10 M) [7]
berotralstat Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibition 7.3 – 10.0 pKi 3
⤷ pKi 7.3 – 10.0 (Ki 5x10-8 – 1x10-10 M) [3]
Description: Ki determined in a biochemical assay, using example 52h which has no specified stereochemistry.
milvexian Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.4 pKi 2
⤷ pKi 7.4 (Ki 4.4x10-8 M) [2]
avoralstat Small molecule or natural product Ligand has a PDB structure Hs Inhibition 8.7 pIC50 5
⤷ pIC50 8.7 (IC50 2x10-9 M) [5]
sebetralstat Small molecule or natural product Hs Inhibition 8.2 pIC50 1
⤷ pIC50 8.2 (IC50 6x10-9 M) [1]
Antibodies
Key to terms and symbols Click column headers to sort
Antibody Sp. Action Value Parameter Reference
lanadelumab Peptide Approved drug Primary target of this compound Hs Binding 10.1 pIC50 6
⤷ pIC50 10.1 (IC50 9x10-11 M) [6]
Immunopharmacology Comments
Kallikrein is a therapeutic target for the treament of the inflammatory attacks that cause vascular and organ damage in hereditary angioedema (HAE) [4]. The small molecule inhibitor berotralstat and the monoclonal lanadelumab are already used clinically for this indication. A CRISPR-Cas9 KLKB1 gene-disrupting therapeutic is in develoment [4].
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Immune regulation
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Prekallikrein deficiency
Synonyms: Fletcher factor deficiency
OMIM: 612423
Orphanet: ORPHA749

References

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1. Davie RL, Edwards HJ, Evans DM, Hodgson ST, Stocks MJ, Smith AJ, Rushbrooke LJ, Pethen SJ, Roe MB, Clark DE et al.. (2022) Sebetralstat (KVD900): A Potent and Selective Small Molecule Plasma Kallikrein Inhibitor Featuring a Novel P1 Group as a Potential Oral On-Demand Treatment for Hereditary Angioedema. J Med Chem, 65 (20): 13629-13644. [PMID:36251573]

2. Dilger AK, Pabbisetty KB, Corte JR, De Lucca I, Fang T, Yang W, Pinto DJP, Wang Y, Zhu Y, Mathur A et al.. (2022) Discovery of Milvexian, a High-Affinity, Orally Bioavailable Inhibitor of Factor XIa in Clinical Studies for Antithrombotic Therapy. J Med Chem, 65 (3): 1770-1785. [PMID:34494428]

3. Kotian PL, Babu YS, Wu M, Chintareddy VR, Kumar VS, Zhang W. (2015) Human plasma kallikrein inhibitors. Patent number: WO2015134998A1. Assignee: Biocryst Pharmaceuticals. Priority date: 07/03/2014. Publication date: 11/09/2015.

4. Longhurst HJ, Lindsay K, Petersen RS, Fijen LM, Gurugama P, Maag D, Butler JS, Shah MY, Golden A, Xu Y et al.. (2024) CRISPR-Cas9 In Vivo Gene Editing of KLKB1 for Hereditary Angioedema. N Engl J Med, 390 (5): 432-441. [PMID:38294975]

5. Partridge JR, Choy RM, Silva-Garcia A, Yu C, Li Z, Sham H, Metcalf B. (2019) Structures of full-length plasma kallikrein bound to highly specific inhibitors describe a new mode of targeted inhibition. J Struct Biol, 206 (2): 170-182. [PMID:30876891]

6. Sexton DJ, Viswanathan M. (2014) Plasma kallikrein binding proteins. Patent number: US8816055 B2. Assignee: Dyax Corp.. Priority date: 06/01/2011. Publication date: 26/08/2014.

7. Young WB, Rai R, Shrader WD, Burgess-Henry J, Hu H, Elrod KC, Sprengeler PA, Katz BA, Sukbuntherng J, Mordenti J. (2006) Small molecule inhibitors of plasma kallikrein. Bioorg Med Chem Lett, 16 (7): 2034-6. [PMID:16413183]

How to cite this page

S1: Chymotrypsin: kallikrein B1. Last modified on 06/02/2024. Accessed on 19/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2379.