4829 T3D4774 Cladribine An antineoplastic agent used in the treatment of lymphoproliferative diseases including hairy-cell leukemia. 4291-63-8 20279 C10H12ClN5O3 White powder. 215°C 6.35e+00 g/L Oral bioavailability is 34 to 48%. Cladribine is structurally related to fludarabine and pentostatin but has a different mechanism of action. Although the exact mechanism of action has not been fully determined, evidence shows that cladribine is phosphorylated by deoxycytidine kinase to the nucleotidecladribine triphosphate (CdATP; 2-chloro-2ду_-deoxyadenosine 5ду_-triphosphate), which accumulates and is incorporated into DNA in cells such as lymphocytes that contain high levels of deoxycytidine kinase and low levels of deoxynucleotidase, resulting in DNA strand breakage and inhibition of DNA synthesis and repair. High levels of CdATP also appear to inhibit ribonucleotide reductase, which leads to an imbalance in triphosphorylated deoxynucleotide (dNTP) pools and subsequent DNA strand breaks, inhibition of DNA synthesis and repair, nicotinamide adenine dinucleotide (NAD) and ATP depletion, and cell death. Unlike other antimetabolite drugs, cladribine has cytotoxic effects on resting as well as proliferating lymphocytes. However, it does cause cells to accumulate at the G1/S phase junction, suggesting that cytotoxicity is associated with events critical to cell entry into S phase. It also binds purine nucleoside phosphorylase (PNP), however no relationship between this binding and a mechanism of action has been established. Metabolized in all cells with deoxycytidine kinase activity to 2-chloro-2'-deoxyadenosine-5'-triphosphate Half Life: 5.4 hours No indication of carcinogenicity to humans (not listed by IARC). For the treatment of active hairy cell leukemia (leukemic reticuloendotheliosis) as defined by clinically significant anemia, neutropenia, thrombocytopenia, or disease-related symptoms. Also used as an alternative agent for the treatment of chronic lymphocytic leukemia (CLL), low-grade non-Hodgkin's lymphoma, and cutaneous T-cell lymphoma. Symptoms of overdose include irreversible neurologic toxicity (paraparesis/quadriparesis), acute nephrotoxicity, and severe bone marrow suppression resulting in neutropenia, anemia and thrombocytopenia. 2014-09-11T05:16:01Z 2014-12-24T20:26:57Z Cladribine 567361 DB00242 CL9 true [H][C@]1(O)C[C@@]([H])(O[C@]1([H])CO)N1C=NC2=C(N)N=C(Cl)N=C12 C10H12ClN5O3 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/s1 InChIKey=PTOAARAWEBMLNO-KVQBGUIXSA-N 285.687 285.062866982 Exogenous Solid -0.1 HMDB14387 CHEMBL1619 19105 <p>Szepsel Gerszberg, &#8220;Method for the production of 2-chloro-2&apos; -deoxyadenosine (cladribine) and its 3,5-di-O-p-toluoyl derivative.&#8221; U.S. Patent US20020052491, issued May 02, 2002.</p>