Cladribine

USDailyMed:Cladribine AU:D L01BB04(WHO) (parenteral)L04AA40(WHO) (oralformultiple sclerosis) AU:S4(Prescription only)CA:℞-onlyUK:POM(Prescription only)US:℞-onlyEU:Rx-only Intravenous and subcutaneous bolus injection: 15-18% is excreted unchanged 5-(6-Amino-2-chloro-purin-9-yl)-2-(hydroxymethyl)oxolan-3-ol 4291-63-8Y 20279 4799 DB00242Y 19105Y 47M74X9YT5 D01370Y CHEBI:567361Y ChEMBL1619Y DTXSID8022828 Interactive image Clc1nc(c2ncn(c2n1)[C@@H]3O[C@@H]([C@@H](O)C3)CO)N InChI=1S/C10H12ClN5O3/c11-10-14-8(12)7-9(15-10)16(3-13-7)6-1-4(18)5(2-17)19-6/h3-6,17-18H,1-2H2,(H2,12,14,15)/t4-,5+,6+/m0/s1YKey:PTOAARAWEBMLNO-KVQBGUIXSA-NY Cladribine, sold under the brand nameLeustatin, among others, is a medication used to treathairy cell leukemia(formally named leukemic reticuloendotheliosis) andB-cell chronic lymphocytic leukemia.Cladribine, sold under the brand nameMavenclad, is used for the treatment of adults with highly active forms ofrelapsing-remitting multiple sclerosis. Cladribine is a purine analogue that selectively targets and suppresseslymphocytesimplicated in the underlying pathogenesis ofmultiple sclerosisand B-cell leukaemia.Chemically, it mimics thenucleosidedeoxyadenosine. However, unlike deoxyadenosine, it is relatively resistant to breakdown by the enzymeadenosine deaminase, which causes it to accumulate in targeted cells and interfere with the cell's ability to process DNA.Cladribine is taken up by cells via transporter proteins. Once inside a cell, cladribine undergoes phosphorylation by the enzymedeoxycytidine kinase(DCK) to produce mononucleotide 2-chlorodeoxyadenosine 5'monophosphate (2-CdAMP), which is subsequently phosphorylated to the triphosphorylated active compound 2-chlorodeoxyadenosine 5'triphosphate (2-CdATP). Activated cladribine is incorporated into cellular DNA, which triggersapoptosis. Accumulation of cladribine into cells is dependent on the ratio of DCK and5'-nucleotidase(5'-NT), which breaks down and inactivates the compound. This ratio differs between cell types, with high levels in T and B lymphocytes, resulting in selective targeting of these cells. In contrast, DCK:5'NT is relatively low in other cell types, thus sparing numerous non-haematological cells. It is on theWorld Health Organization's List of Essential Medicines.