KLKB1

Synonyms

EC:3.4.21.34, Fletcher factor, Plasma prekallikrein, Kallikrein B1, Kallikrein B, Plasma (Fletcher Factor) 1, Kininogenin, KLK3, PKK, Plasma Kallikrein, EC 3.4.21.34, PKKD, PPK, EC 3.4.21, KLKB1

Description

KLKB1 (Plasma kallikrein) 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 play a role in the renin-angiotensin system by converting prorenin into renin.

KO Status

RenMab: F2 (-/-)

Drug Information

Launched drugs: 2
Drugs in clinical trials: 7
Latest Research Phase: Approved

Drug Name

Code

Phase

Company

Indications

Clinical Trials

Berotralstat

BCX-7353

Approved

Biocryst Pharmaceuticals

Angioedemas, Hereditary

Lanadelumab

SHP-643, DX-2930, TAK-743, 2372V1TKXK (UNII code), X124-G01

Approved

Dyax Pharma

Coronavirus Disease 2019 (COVID-19), Angioedemas, Hereditary, Angioedema

Ecallantide

DX-88, EPI-KAL2, FOV-2302, CB-500929

Approved

Dyax Pharma

Macular Edema, Blood Loss, Surgical, Angioedemas, Hereditary, Retinal Vein Occlusion, Angioedema

KVD-900

KVD-900

Phase 2 Clinical

Kalvista Pharmaceuticals

Angioedemas, Hereditary

KVD-001

KVD-001

Phase 2 Clinical

Vantia

Diabetic macular oedema

THR-149

TG-758, THR-149

Phase 2 Clinical

Bicycle Therapeutics, Thrombogenics Inc

Diabetic macular oedema, Diabetic Retinopathy, Diabetes Mellitus

ATN-249

ATN-249

Phase 1 Clinical

Attune Pharmaceuticals

Angioedemas, Hereditary

KVD-824

KVD-824

Phase 1 Clinical

Vantia

Diabetic macular oedema, Angioedemas, Hereditary

MDPK-67b

DM-107, MDPK-67, MDPK-67b

Phase 1 Clinical

Med Discovery

Neutropenia, Netherton Syndrome, Prostatic Neoplasms, Dermatitis, Atopic

NTLA-2002

NTLA-2002

Preclinical

Intellia Therapeutics Inc

Angioedemas, Hereditary

References


Title

Authors

Source

Complete sequencing and characterization of 21,243 full-length human cDNAs

Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., Sugano S.,

Nat. Genet. 36:40-45(2004)

Generation and annotation of the DNA sequences of human chromosomes 2 and 4

Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H., Wilson R.K.,

Nature 434:724-731(2005)

The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)

The MGC Project Team,

Genome Res. 14:2121-2127(2004)

Location of the disulfide bonds in human plasma prekallikrein: the presence of four novel apple domains in the amino-terminal portion of the molecule

McMullen B.A., Fujikawa K., Davie E.W.,

Biochemistry 30:2050-2056(1991)

Inactivation of human plasma kallikrein and factor XIa by protein C inhibitor

Meijers J.C., Kanters D.H., Vlooswijk R.A., van Erp H.E., Hessing M., Bouma B.N.,

Biochemistry 27:4231-4237(1988)

Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry

Zhang H., Li X.-J., Martin D.B., Aebersold R.,

Nat. Biotechnol. 21:660-666(2003)

Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry

Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.,

J. Proteome Res. 4:2070-2080(2005)

Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry

Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.,

J. Proteome Res. 8:651-661(2009)

Severe prekallikrein (Fletcher factor) deficiency due to a compound heterozygosis (383Trp stop codon and Cys529Tyr)

Lombardi A.M., Sartori M.T., Cabrio L., Fadin M., Zanon E., Girolami A.,

Thromb. Haemost. 90:1040-1045(2003)

A new type of plasma prekallikrein deficiency associated with homozygosity for Gly104Arg and Asn124Ser in apple domain 2 of the heavy-chain region

Katsuda I., Maruyama F., Ezaki K., Sawamura T., Ichihara Y.,

Eur. J. Haematol. 79:59-68(2007)