Sprycel

Dasatinib (Sprycel ) 12 inhibits Btk (IC50 = 5 nM) as well as the basal and lipopolysaccharide (LPS)-induced secretion of TNFa and IL-6 in U937 cells [65]. However, dasatinib s promiscuity [66] makes it difficult to ascribe these functional effects to direct Btk inhibition. The dasatinib-Btk(Y551E) crystal structure indicates binding to an active conformation, similar to that observed with Abl [43]. LFM-A13,13, was first described as a Btk inhibitor more than 10 years ago [67], although its poor Btk activity (IC50 = 2.5-17 /iM) and selectivity [68] require that caution be taken in interpreting functional effects. 

Most advanced clinical trial Investigational Drugs Database (http //www.iddb3.com) NEXAVAR , approved by FDA, December 2005 SUTENT , approved by FDA, January 2006 SPRYCEL , approved by FDA, Jime 2006... 

Pyrimidinylaminothiazole Template-Based Inhibitor BMS-354825 (Dasatinib, Sprycel )... 

Note added in proof On June 29, 2006 the Food and Drug Administration (FDA) granted approval for dasatinib (Sprycel) [152]. 

The two compounds in the most advanced stages of development included dasa-tinib (BMS354825, Sprycel ) and nilotinib (AMN107, Tasigna ) (Fig. 5). Dasatinib... 

Cortes J, Guilhot F, Rosti Get al. Dasatinib (SPRYCEL) in patients (pts) with chronic myelogenous leukemia in aeeelerated phase (AP-CML) that is imatinib-resistant (TM-R) or intolerant (IM-I) updated results of the CA180-005 START-A phase 11 study (Abstract 2160). Blood 2006 108 613a. Cortes J, Rousselot R Kim DW et al. Dasatinib induces complete hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in blast crisis. Blood 2007 109 3207-3213. 

Shah N, Pasquini R, Rousselot P et al. Dasatinib (SPRYCEL) vs. escalated dose of imatinib (IM) in patients (pts) with ehronie phase chronic myeloid leukemia (CP-CML) resistant to imatinib results of the CA180-017 START-R randomized study (Abstract 167). B/ooii2006 108 53a. 

USAN Dasanitib Trade name Sprycel Bristol-Myers Squibb Approved 2006... 

Trade name Sprycel (Bristol-Myers Squibb)... 

Dasatinib (Sprycel) Bcr-Abl, SRC, LCK, YES, FYN, c-KIT, EPHA2, and PDGFRp 2006 CV TBP, J,hERG current, APD ECG in monkey— no effect 6-month rat, 9-month monkey GI, kidney, heart, liver, lymphoid/hematopoietic, adrenals, thyroid, pancreas, lung QT Prolongation, CHF, LV dysfunction, MI, hemorrhage. Pulmonary Arterial Hypertension (PAH), fluid retention, myelosuppression... 

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