Caplacizumab binds VWF

Stable Identifier
R-HSA-9822734
Type
Reaction [binding]
Species
Homo sapiens
Compartment
extracellular region
ReviewStatus
5/5
Locations in the PathwayBrowser
Expand all
General
SVG | 
PNG
Low
Medium
High
 | PPTX  | SBGN
Caplacizumab binds VWF
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
Caplacizumab (CABLIVI®, also known as ALX-0081) is a bivalent humanized antibody fragment consisting of a single variable domain (also called nanobody) that targets von Willebrand factor (VWF) (Ulrichts H et al., 2011; van Loon JE et al., 2011). Caplacizumab binds the A1 domain of VWF with high affinity (Ulrichts H et al., 2011; Lee HT et al., 2021). This interaction inhibits binding between VWF and the platelet glycoprotein Ib (GPIb) receptor complex preventing VWF-mediated tethering of platelets to the damaged vessel wall. Structural insights into the mechanism of action suggest that caplacizumab acts by stabilizing an inactive conformation of VWF, which does not interact with platelets, rather than competing with GPIb (Lee HT et al., 2021). Caplacizumab is the Food and Drug Administration (FDA) approved drug to treat thrombotic thrombocytopenic purpura (TTP), a clinical condition associated with immune-mediated deficiency of VWF–cleaving protease ADAMTS13 (Lämmle B 2016; Scully M et al., 2019; Hollifield AL et al., 2020; Peyvandi F et al., 2021).
Literature References
PubMed ID Title Journal Year
21655675 The in vitro effect of the new antithrombotic drug candidate ALX-0081 on blood samples of patients undergoing percutaneous coronary intervention

van Loon, JE, de Jaegere, PP, Ulrichts, H, van Vliet, HH, de Maat, MP, de Groot, PG, Simoons, ML, Leebeek, FW

Thromb Haemost 2011
32588878 Caplacizumab: an anti-von Willebrand factor antibody for the treatment of thrombotic thrombocytopenic purpura

Hollifield, AL, Arnall, JR, Moore, DC

Am J Health Syst Pharm 2020
21576702 Antithrombotic drug candidate ALX-0081 shows superior preclinical efficacy and safety compared with currently marketed antiplatelet drugs

Ulrichts, H, Silence, K, Schoolmeester, A, de Jaegere, P, Rossenu, S, Roodt, J, Priem, S, Lauwereys, M, Casteels, P, Van Bockstaele, F, Verschueren, K, Stanssens, P, Baumeister, J, Holz, JB

Blood 2011
34144500 High-resolution structure of the vWF A1 domain in complex with caplacizumab, the first nanobody-based medicine for treating acquired TTP

Lee, HT, Park, UB, Jeong, TJ, Gu, N, Lee, SH, Kim, Y, Heo, YS

Biochem Biophys Res Commun 2021
Participants
Input
Output
Participates
as an event of
Disease
Name Identifier Synonyms
autoimmune thrombocytopenic purpura DOID:8924 idiopathic thrombocytopenic purpura, werlhof's disease, Ideopath thrombocytopenic pur, Autoimmune thrombocytopenic purpura, Idiopathic purpura, Immune thrombocytopenic purpura, primary thrombocytopenic purpura
Cross References
Mondo
Authored
Shamovsky, V  (2022-12-25)
Reviewed
Gao, R  (2023-11-07)
Created
Shamovsky, V  (2022-12-27)
Cite Us!