Dasatinib

488.007

488.01

801-607-0

X78UG0A0RN

759877|732517

DTXSID4040979

C74556

L01EA02|L01XE06|L - Antineoplastic and immunomodulating agents

29341000

135

3.6

Solid

1.4±0.1 g/cm3

280 - 286 °C

1.688

1.28e-02 g/L

3

P201, P202, P260, P263, P264, P270, P273, P280, P281, P301+P310, P302+P352, P305+P351+P338, P308+P313, P309+P311, P310, P314, P321, P330, P332+P313, P362, P391, P405, P501

H301

|Danger|H301 (99.02%): Toxic if swallowed [Danger Acute toxicity, oral]|P201, P202, P260, P264, P270, P273, P280, P281, P301+P310, P302+P352, P305+P351+P338, P308+P313, P310, P314, P321, P330, P332+P313, P362, P391, P405, and P501|Aggregated GHS information provided by 102 companies from 8 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Acute overdose in animals was associated with cardiotoxicity.

In large clinical trials, elevations in serum aminotransferase levels during dasatinib therapy occurred in up to 50% of patients, but were usually mild and self-limited. Elevations above 5 times the upper limit of normal (ULN) occurred in 1% to 9% of patients and generally responded to dose adjustment or temporary discontinuation and restarting at a lower dose, which is recommended if liver test results are markedly elevated (ALT or AST persistently greater than 5 times ULN or bilirubin more than 3 times ULN). While episodes of marked serum aminotransferase elevations with symptoms have been reported, there have been no published reports of clinically apparent liver injury with jaundice attributed to dasatinib therapy. Certainly other tyrosine kinase receptor inhibitors used in the therapy of CML such as imatinib, nilotinib and ponatinib have been associated with cases of acute liver injury with jaundice. With these agents, the liver injury typically arises after several months of therapy and the pattern of serum enzyme elevations is typically hepatocellular. Immunoallergic features (rash, fever and eosinophilia) and autoantibody formation are usually not present.

96%

For the treatment of adults with chronic, accelerated, or myeloid or lymphoid blast phase chronic myeloid leukemia with resistance or intolerance to prior therapy. Also indicated for the treatment of adults with Philadelphia chromosome-positive acute lymphoblastic leukemia with resistance or intolerance to prior therapy.|FDA Label|Sprycel is indicated for the treatment of paediatric patients with:newly diagnosed Philadelphia chromosome-positive chronic myelogenous leukaemia in chronic phase (Ph+ CML CP) or Ph+ CML CP resistant or intolerant to prior therapy including imatinib.newly diagnosed Ph+ acute lymphoblastic leukaemia (ALL) in combination with chemotherapy.Sprycel is indicated for the treatment of adult patients with:newly diagnosed Philadelphia-chromosome-positive (Ph+) chronic myelogenous leukaemia (CML) in the chronic phase;chronic, accelerated or blast phase CML with resistance or intolerance to prior therapy including imatinib mesilate;Ph+ acute lymphoblastic leukaemia (ALL) and lymphoid blast CML with resistance or intolerance to prior therapy.Sprycel is indicated for the treatment of paediatric patients with:newly diagnosed Ph+ CML in chronic phase (Ph+ CML-CP) or Ph+ CML-CP resistant or intolerant to prior therapy including imatinib.|Treatment of Philadelphia-chromosome (BCR-ABL translocation)-positive acute lymphoblastic leukaemia, Treatment of Philadelphia-chromosome (BCR-ABL translocation)-positive chronic myeloid leukaemia|Drug: Dasatinib

Dasatinib is a selective tyrosine kinase receptor inhibitor that is used in the therapy of chronic myelogenous leukemia (CML) positive for the Philadelphia chromosome. Dasatinib is commonly associated with transient elevations in serum aminotransferase levels during treatment, but with only rare instances of clinically apparent acute liver injury.

Antineoplastic Agents

Dasatinib is an oral dual BCR/ABL and Src family tyrosine kinase inhibitor

Agents that inhibit PROTEIN KINASES. (See all compounds classified as Protein Kinase Inhibitors.)|Substances that inhibit or prevent the proliferation of NEOPLASMS. (See all compounds classified as Antineoplastic Agents.)

Dasatinib is extensively metabolized in humans, primarily by the cytochrome P450 enzyme 3A4. Elimination is primarily via the feces.|2505 L

Dasatinib is extensively metabolized in humans, primarily by the cytochrome P450 enzyme 3A4

The overall mean terminal half-life of dasatinib is 3-5 hours.

Dasatinib, at nanomolar concentrations, inhibits the following kinases: BCR-ABL, SRC family (SRC, LCK, YES, FYN), c-KIT, EPHA2, and PDGFRβ. Based on modeling studies, dasatinib is predicted to bind to multiple conformations of the ABL kinase. In vitro, dasatinib was active in leukemic cell lines representing variants of imatinib mesylate sensitive and resistant disease. Dasatinib inhibited the growth of chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL) cell lines overexpressing BCR-ABL. Under the conditions of the assays, dasatinib was able to overcome imatinib resistance resulting from BCR-ABL kinase domain mutations, activation of alternate signaling pathways involving the SRC family kinases (LYN, HCK), and multi-drug resistance gene overexpression.

(18F)-N-(2-chloro-6-methylphenyl)-2-(6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-ylamino)thiazole-5-carboxamide

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