Dasatinib

Dasatinib
Clinical data

Trade names	Sprycel
AHFS/Drugs.com	Monograph
MedlinePlus	a607063
License data	EU EMA: Sprycel US FDA: Dasatinib
Pregnancy category	AU: D US: D (Evidence of risk)
Routes of administration	Oral (tablets)
ATC code	L01XE06 (WHO)
Legal status
Legal status	US: ℞-only In general: ℞ (Prescription only)
Pharmacokinetic data
Protein binding	96%
Metabolism	Hepatic
Biological half-life	1.3 to 5 hours
Excretion	Faecal (85%), renal (4%)
Identifiers
IUPAC name N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)- 1-piperazinyl]-2-methyl-4-pyrimidinyl]amino]-5-thiazole carboxamide monohydrate
CAS Number	302962-49-8^Y
PubChem CID	3062316
IUPHAR/BPS	5678
DrugBank	DB01254^Y
ChemSpider	2323020^Y
UNII	X78UG0A0RN
KEGG	D03658^N
ChEBI	CHEBI:49375^Y
ChEMBL	CHEMBL1421^Y
ECHA InfoCard	100.228.321
Chemical and physical data
Formula	C₂₂H₂₆ClN₇O₂S
Molar mass	488.01 g/mol
3D model (Jmol)	Interactive image
SMILES Cc1cccc(c1NC(=O)c2cnc(s2)Nc3cc(nc(n3)C)N4CCN(CC4)CCO)Cl
InChI InChI=1S/C22H26ClN7O2S/c1-14-4-3-5-16(23)20(14)28-21(32)17-13-24-22(33-17)27-18-12-19(26-15(2)25-18)30-8-6-29(7-9-30)10-11-31/h3-5,12-13,31H,6-11H2,1-2H3,(H,28,32)(H,24,25,26,27)^Y Key:ZBNZXTGUTAYRHI-UHFFFAOYSA-N^Y= ^Y
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Dasatinib, previously known as BMS-354825, is a cancer drug produced by Bristol-Myers Squibb and sold under the trade name Sprycel. Dasatinib is an oral Bcr-Abl tyrosine kinase inhibitor (inhibits the "Philadelphia chromosome") and Src family tyrosine kinase inhibitor approved for first line use in patients with chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). It is being evaluated for use in numerous other cancers, including advanced prostate cancer.

In a Phase I dose escalation study published in June 2006, dasatinib was tested in patients who were resistant to or who could not tolerate imatinib. Complete hematological responses were seen in 37 of 40 patients with chronic-phase CML. Major hematologic responses were seen in 31 of 44 patients with accelerated-phase CML, CML in blast crisis, or Ph+ ALL.

The main targets of dasatinib are BCR/Abl (the "Philadelphia chromosome"), Src, c-Kit, ephrin receptors, and several other tyrosine kinases.

Responses were maintained in 95% of patients with chronic-phase CML, with a median follow-up time of >12 months. In patients with accelerated-phase CML, 82% remained in remission, although with a median follow-up of only 5 months. Nearly all patients with CML in blast crisis or Ph+ ALL relapsed within 6 months.

Responses were seen in patients with all BCR/Abl genotypes, with the exception of T315I mutation, which confers resistance to dasatinib, nilotinib and imatinib in vitro.

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