DASATINIB ANHYDROUS

Details

Stereochemistry	ACHIRAL
Molecular Formula	C22H26ClN7O2S
Molecular Weight	488.006
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=NC(NC2=NC=C(S2)C(=O)NC3=C(Cl)C=CC=C3C)=CC(=N1)N4CCN(CCO)CC4

InChI

InChIKey=ZBNZXTGUTAYRHI-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Molecular Formula	C22H26ClN7O2S
Molecular Weight	488.006
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021986s018lbl.pdf
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/16542059

Dasatinib [BMS 354825] is an orally active, small molecule, dual inhibitor of both SRC and ABL kinases that is under development with Bristol-Myers Squibb for the treatment of patients with chronic myelogenous leukaemia (CML) and imatinib-acquired resistance/intolerance. It’s used 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. While imatinib remains a frontline therapy for CML, patients with advanced disease frequently develop resistance to imatinib therapy through multiple mechanisms. Dasatinib is also undergoing preclinical evaluation for its potential as a therapy against multiple myeloma. Bristol-Myers Squibb has a composition-of-matter patent covering this research approach that will expire in 2020. 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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
SRC 5 Target ID: CHEMBL2363074 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17701954	Inhibitor 8146
Stem cell growth factor receptor 51 Target ID: CHEMBL1936 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17701954	Inhibitor 8146
Ephrin type-A receptor 2 6 Target ID: CHEMBL2068 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17701954	Inhibitor 8146
Platelet-derived growth factor receptor beta 54 Target ID: CHEMBL1913 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17701954	Inhibitor 8146
Tyrosine-protein kinase ABL 29 Target ID: CHEMBL1862 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17701954	Inhibitor 8146

Conditions

Condition	Modality	Targets	Highest Phase	Product
Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) 3 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021986s018lbl.pdf	Primary		Approved 8307	SPRYCEL Approved Use SPRYCEL® (dasatinib) is indicated for the treatment of adults with newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase. The effectiveness of SPRYCEL is based on cytogenetic response and major molecular response rates [see Clinical Studies (14.1) Launch Date 1.15145284E12
Acute lymphoblastic leukemia 27 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021986s018lbl.pdf	Primary		Approved 8307	SPRYCEL Approved Use SPRYCEL® (dasatinib) is indicated for the treatment of adults with newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase. The effectiveness of SPRYCEL is based on cytogenetic response and major molecular response rates [see Clinical Studies (14.1) Launch Date 1.15145284E12

C_max

Value	Dose	Co-administered	Analyte	Population
82.2 ng/mL DRUG LABEL https://packageinserts.bms.com/pi/pi_sprycel.pdf	100 mg 1 times / day steady-state, oral dose: 100 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		DASATINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
397 ng × h/mL DRUG LABEL https://packageinserts.bms.com/pi/pi_sprycel.pdf	100 mg 1 times / day steady-state, oral dose: 100 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		DASATINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
3 h DRUG LABEL https://packageinserts.bms.com/pi/pi_sprycel.pdf	100 mg 1 times / day steady-state, oral dose: 100 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		DASATINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
6% EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/17429625			DASATINIB plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
90 mg 2 times / day steady, oral Higher than recommended Dose: 90 mg, 2 times / day Route: oral Route: steady Dose: 90 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19789325/ Page: Table 3	unhealthy, 32-81 years n = 6 Health Status: unhealthy Condition: metastatic solid tumors Age Group: 32-81 years Sex: M+F Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/19789325/ Page: Table 3	DLT: Dehydration, Hyponatremia... Other AEs: Fatigue, Nausea... Dose limiting toxicities: Dehydration (grade 3, 1 patient) Hyponatremia (grade 3, 1 patient) Other AEs: Fatigue (grade 1-2, 3 patients) Nausea (grade 1-2, 1 patient) Diarrhea (grade 1-2, 1 patient) Anorexia (grade 1-2, 1 patient) Lethargy (grade 1-2, 2 patients) Headache (grade 1-2, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/19789325/ Page: Table 3
160 mg 2 times / day steady, oral Highest studied dose Dose: 160 mg, 2 times / day Route: oral Route: steady Dose: 160 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19789325/ Page: Table 3	unhealthy, 32-81 years n = 4 Health Status: unhealthy Condition: metastatic solid tumors Age Group: 32-81 years Sex: M+F Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/19789325/ Page: Table 3	DLT: Rash, Lethargy... Other AEs: Nausea, Fatigue... Dose limiting toxicities: Rash (grade 2, 3 patients) Lethargy (grade 3, 3 patients) Bleeding time prolonged (grade 3, 1 patient) Hypocalcemia (grade 3, 1 patient) Other AEs: Nausea (grade 1-2, 4 patients) Fatigue (grade 1-2, 1 patient) Diarrhea (grade 1-2, 3 patients) Vomiting (grade 1-2, 2 patients) Anorexia (grade 1-2, 2 patients) Lethargy (grade 1-2, 2 patients) Headache (grade 1-2, 1 patient) Pyrexia (grade 1-2, 1 patient) Chills (grade 1-2, 3 patients) Proteinuria (grade 1-2, 2 patients) Anorexia (grade 3-4, 1 patient) Lethargy (grade 3-4, 1 patient) Proteinuria (grade 3-4, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/19789325/ Page: Table 3
120 mg 2 times / day steady, oral MTD Dose: 120 mg, 2 times / day Route: oral Route: steady Dose: 120 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19789325/ Page: Table 3	unhealthy, 32-81 years n = 9 Health Status: unhealthy Condition: metastatic solid tumors Age Group: 32-81 years Sex: M+F Population Size: 9 Sources: https://pubmed.ncbi.nlm.nih.gov/19789325/ Page: Table 3	DLT: Tumor lysis syndrome... Other AEs: Nausea, Fatigue... Dose limiting toxicities: Tumor lysis syndrome (grade 3, 1 patient) Other AEs: Nausea (grade 1-2, 7 patients) Fatigue (grade 1-2, 2 patients) Diarrhea (grade 1-2, 4 patients) Vomiting (grade 1-2, 4 patients) Anorexia (grade 1-2, 1 patient) Lethargy (grade 1-2, 2 patients) Headache (grade 1-2, 2 patients) Pyrexia (grade 1-2, 1 patient) Chills (grade 1-2, 1 patient) Proteinuria (grade 1-2, 1 patient) Nausea (grade 3-4, 1 patient) Vomiting (grade 3-4, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/19789325/ Page: Table 3
70 mg 2 times / day steady, oral MTD Dose: 70 mg, 2 times / day Route: oral Route: steady Dose: 70 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19789325/ Page: Table 4	unhealthy, 32-81 years n = 5 Health Status: unhealthy Condition: metastatic solid tumors Age Group: 32-81 years Sex: M+F Population Size: 5 Sources: https://pubmed.ncbi.nlm.nih.gov/19789325/ Page: Table 4	Other AEs: Nausea, Anorexia... Other AEs: Nausea (grade 1-2, 2 patients) Anorexia (grade 1-2, 4 patients) Fatigue (grade 1-2, 1 patient) Diarrhea (grade 1-2, 1 patient) Lethargy (grade 1-2, 2 patients) Vomiting (grade 1-2, 1 patient) Headache (grade 1-2, 2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/19789325/ Page: Table 4
50 mg 2 times / day steady, oral Recommended Dose: 50 mg, 2 times / day Route: oral Route: steady Dose: 50 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19789325/ Page: Table 3	unhealthy, 32-81 years n = 3 Health Status: unhealthy Condition: metastatic solid tumors Age Group: 32-81 years Sex: M+F Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/19789325/ Page: Table 3	Other AEs: Nausea, Fatigue... Other AEs: Nausea (grade 1-2, 1 patient) Fatigue (grade 1-2, 2 patients) Diarrhea (grade 1-2, 1 patient) Vomiting (grade 1-2, 1 patient) Anorexia (grade 1-2, 1 patient) Lethargy (grade 1-2, 1 patient) Pyrexia (grade 1-2, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/19789325/ Page: Table 3
70 mg 2 times / day steady, oral Recommended Dose: 70 mg, 2 times / day Route: oral Route: steady Dose: 70 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19789325/ Page: Table 3	unhealthy, 32-81 years n = 4 Health Status: unhealthy Condition: metastatic solid tumors Age Group: 32-81 years Sex: M+F Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/19789325/ Page: Table 3	Other AEs: Nausea, Fatigue... Other AEs: Nausea (grade 1-2, 3 patients) Fatigue (grade 1-2, 3 patients) Diarrhea (grade 1-2, 1 patient) Anorexia (grade 1-2, 2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/19789325/ Page: Table 3
100 mg 2 times / day steady, oral Studied dose Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19789325/ Page: Table 4	unhealthy, 32-81 years n = 13 Health Status: unhealthy Condition: metastatic solid tumors Age Group: 32-81 years Sex: M+F Population Size: 13 Sources: https://pubmed.ncbi.nlm.nih.gov/19789325/ Page: Table 4	DLT: Toxic myocarditis, T wave inversion... Dose limiting toxicities: Toxic myocarditis (grade 2, 1 patient) T wave inversion (grade 2, 1 patient) Cardiac troponin increased (grade 4, 1 patient) Dyspnea (grade 3, 6 patients) Constipation (grade 3, 6 patients) Proteinuria (grade 2, 6 patients) Fatigue (grade 4, 6 patients) Lethargy (grade 3, 6 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/19789325/ Page: Table 4
100 mg 2 times / day steady, oral Studied dose Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19789325/ Page: Table 4	unhealthy, 32-81 years n = 17 Health Status: unhealthy Condition: metastatic solid tumors Age Group: 32-81 years Sex: M+F Population Size: 17 Sources: https://pubmed.ncbi.nlm.nih.gov/19789325/ Page: Table 4	Other AEs: Nausea, Anorexia... Other AEs: Nausea (grade 1-2, 7 patients) Anorexia (grade 1-2, 9 patients) Fatigue (grade 1-2, 8 patients) Diarrhea (grade 1-2, 6 patients) Lethargy (grade 1-2, 2 patients) Vomiting (grade 1-2, 3 patients) Headache (grade 1-2, 3 patients) Proteinuria (grade 1-2, 4 patients) Rash (grade 1-2, 3 patients) Pruritus (grade 1-2, 2 patients) Anemia (grade 1-2, 2 patients) Dyspnea (grade 1-2, 2 patients) Fatigue (grade 3-4, 1 patient) Lethargy (grade 3-4, 1 patient) Dyspnea (grade 3-4, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/19789325/ Page: Table 4
120 mg 2 times / day steady, oral Studied dose Dose: 120 mg, 2 times / day Route: oral Route: steady Dose: 120 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19789325/ Page: Table 4	unhealthy, 32-81 years n = 4 Health Status: unhealthy Condition: metastatic solid tumors Age Group: 32-81 years Sex: M+F Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/19789325/ Page: Table 4	DLT: Nausea, Fatigue... Dose limiting toxicities: Nausea (grade 3, 3 patients) Fatigue (grade 3, 3 patients) Rash (grade 3, 1 patient) Proteinuria (grade 2, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/19789325/ Page: Table 4
120 mg 2 times / day steady, oral Studied dose Dose: 120 mg, 2 times / day Route: oral Route: steady Dose: 120 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19789325/ Page: Table 4	unhealthy, 32-81 years n = 5 Health Status: unhealthy Condition: metastatic solid tumors Age Group: 32-81 years Sex: M+F Population Size: 5 Sources: https://pubmed.ncbi.nlm.nih.gov/19789325/ Page: Table 4	Other AEs: Nausea, Anorexia... Other AEs: Nausea (grade 1-2, 2 patients) Anorexia (grade 1-2, 2 patients) Fatigue (grade 1-2, 2 patients) Diarrhea (grade 1-2, 1 patient) Headache (grade 1-2, 1 patient) Proteinuria (grade 1-2, 1 patient) Pruritus (grade 1-2, 1 patient) Anemia (grade 1-2, 1 patient) Nausea (grade 3-4, 1 patient) Rash (grade 3-4, 1 patient) Fatigue (grade 3-4, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/19789325/ Page: Table 4
35 mg 2 times / day steady, oral Studied dose Dose: 35 mg, 2 times / day Route: oral Route: steady Dose: 35 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19789325/ Page: Table 3	unhealthy, 32-81 years n = 7 Health Status: unhealthy Condition: metastatic solid tumors Age Group: 32-81 years Sex: M+F Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/19789325/ Page: Table 3	DLT: Anorexia, Dehydration... Other AEs: Nausea, Fatigue... Dose limiting toxicities: Anorexia (grade 3, 1 patient) Dehydration (grade 3, 1 patient) Other AEs: Nausea (grade 1-2, 4 patients) Fatigue (grade 1-2, 3 patients) Diarrhea (grade 1-2, 3 patients) Vomiting (grade 1-2, 2 patients) Headache (grade 1-2, 1 patient) Pyrexia (grade 1-2, 1 patient) Diarrhea (grade 3-4, 1 patient) Anorexia (grade 3-4, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/19789325/ Page: Table 3
90 mg 2 times / day steady, oral Studied dose Dose: 90 mg, 2 times / day Route: oral Route: steady Dose: 90 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19789325/ Page: Table 4	unhealthy, 32-81 years n = 7 Health Status: unhealthy Condition: metastatic solid tumors Age Group: 32-81 years Sex: M+F Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/19789325/ Page: Table 4	Other AEs: Nausea, Anorexia... Other AEs: Nausea (grade 1-2, 4 patients) Anorexia (grade 1-2, 4 patients) Fatigue (grade 1-2, 2 patients) Diarrhea (grade 1-2, 3 patients) Lethargy (grade 1-2, 3 patients) Vomiting (grade 1-2, 3 patients) Rash (grade 1-2, 2 patients) Pruritus (grade 1-2, 1 patient) Anemia (grade 1-2, 1 patient) Dyspnea (grade 1-2, 1 patient) Proteinuria (grade 3-4, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/19789325/ Page: Table 4

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1670 inhibitor 1532 inducer 753	inhibitor 1695 inducer 372	inhibitor 1789 inducer 97	inhibitor 1570

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1463 CYP2A6 670 CYP2B6 770 CYP2C8 869 CYP2C19 1410 CYP2E1 846 CYP3A5 73 P-gp 1401	FMO3 65	CYP2C19 283 CYP1A2 671 CYP2B6 521

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1620	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33, 34	no [IC50 >50 uM]
CYP2B6 946	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33, 34	no [IC50 >50 uM]
CYP2C19 1484	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33, 34	no [IC50 >50 uM]
CYP2D6 1826	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33, 34	no [IC50 >50 uM]
CYP2E1 929	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33, 34	no [IC50 >50 uM]
CYP1A2 1620	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33.0	no
CYP2B6 946	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33.0	no
CYP2C19 1484	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33.0	no
CYP2C9 1747	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33.0	no
CYP2D6 1826	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33.0	no
CYP3A4 1857	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 8, 33	no
P-gp 1588	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 35.0	no
CYP3A4 1857	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 8, 33	weak [Ki 1.9 uM]
CYP2C8 923	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33, 34	yes [IC50 12 uM]
CYP2A6 702	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33, 34	yes [IC50 35 uM]
CYP2C9 1747	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33, 34	yes [IC50 50 uM]
CYP3A5 130	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33.0	yes

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
FMO3 65	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 6.0	yes
CYP3A4 1670	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 6, 8	yes		yes (co-administration study) Comment: rifampin decreased AUC by 80%; ketoconazole increased dasatinib Cmax by 4-fold and AUC by 5-fold Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 6, 8

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1603	inhibitor 1584 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__PharmR.pdf Page: 34.0

PubMed

Title	Date	PubMed
Discovery of N-(2-chloro-6-methyl- phenyl)-2-(6-(4-(2-hydroxyethyl)- piperazin-1-yl)-2-methylpyrimidin-4- ylamino)thiazole-5-carboxamide (BMS-354825), a dual Src/Abl kinase inhibitor with potent antitumor activity in preclinical assays.	2004 Dec 30	15615512
New generation leukaemia drugs are on their way.	2004 Sep 1	15450235
In vitro activity of Bcr-Abl inhibitors AMN107 and BMS-354825 against clinically relevant imatinib-resistant Abl kinase domain mutants.	2005 Jun 1	15930265
[Tyrosine kinase inhibitors in the therapy of chronic myeloid leukaemia].	2006	17013368
Cancer and kinases: reports from the front line.	2006	16677415
Dasatinib: BMS 354825.	2006	16542059
[Some new findings in the pathogenesis of myeloproliferative disorders and new insight into more effective treatment].	2006	16468234
[New strategies to overcome imatinib resistance in treatment for chronic myelocytic leukemia].	2006 Aug	17236546
Glivec and beyond.	2006 Aug	16998957
KIT mutations in mastocytosis and their potential as therapeutic targets.	2006 Aug	16931294
Tyrosine kinase inhibitors: the next generation.	2006 Aug	16900596
Leukemogenesis induced by wild-type and STI571-resistant BCR/ABL is potently suppressed by C/EBPalpha.	2006 Aug 15	16670262
Dasatinib (BMS-354825) pharmacokinetics and pharmacodynamic biomarkers in animal models predict optimal clinical exposure.	2006 Dec 1	17145844
Novel treatment strategies for chronic myeloid leukemia.	2006 Dec 1	17106016
Structure of the kinase domain of an imatinib-resistant Abl mutant in complex with the Aurora kinase inhibitor VX-680.	2006 Jan 15	16424036
Gateways to clinical trials.	2006 Jun	16845450
Dasatinib-related alveolar pneumonia responsive to corticosteroids.	2006 Jun	16840219
Impact of genetic diagnostics on drug development strategy.	2006 Jun	16699494
The structure of Dasatinib (BMS-354825) bound to activated ABL kinase domain elucidates its inhibitory activity against imatinib-resistant ABL mutants.	2006 Jun 1	16740718
Dasatinib (BMS-354825) targets an earlier progenitor population than imatinib in primary CML but does not eliminate the quiescent fraction.	2006 Jun 1	16469872
AMN107 (nilotinib): a novel and selective inhibitor of BCR-ABL.	2006 Jun 19	16721371
Inhibition of SRC expression and activity inhibits tumor progression and metastasis of human pancreatic adenocarcinoma cells in an orthotopic nude mouse model.	2006 Mar	16507911
The second generation of BCR-ABL tyrosine kinase inhibitors.	2006 May	16757427
Kinase inhibitors in chronic myelogenous leukemia.	2006 May	16728945
New assignments for multitasking signal transduction inhibitors.	2006 May	16497876
Emerging drugs in chronic myelogenous leukaemia.	2006 Nov	17064224
Novel tyrosine kinase inhibitors in chronic myelogenous leukemia.	2006 Nov	16988578
2-aminothiazole as a novel kinase inhibitor template. Structure-activity relationship studies toward the discovery of N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1- piperazinyl)]-2-methyl-4-pyrimidinyl]amino)]-1,3-thiazole-5-carboxamide (dasatinib, BMS-354825) as a potent pan-Src kinase inhibitor.	2006 Nov 16	17154512
The FDA approves new leukemia drug; expands use of current drug.	2006 Nov-Dec	17338066
Gateways to clinical trials.	2006 Oct	17136234
New tyrosine kinase inhibitors in the treatment of chronic myeloid leukemia.	2006 Oct	17076652
Cotreatment with vorinostat (suberoylanilide hydroxamic acid) enhances activity of dasatinib (BMS-354825) against imatinib mesylate-sensitive or imatinib mesylate-resistant chronic myelogenous leukemia cells.	2006 Oct 1	17020995
Novel approaches in the treatment of systemic mastocytosis.	2006 Oct 1	16948123
ReSETting PP2A tumour suppressor activity in blast crisis and imatinib-resistant chronic myelogenous leukaemia.	2006 Oct 9	16953242
Dasatinib.	2006 Sep	17001803
Sequential emergence of ABL-kinase mutations with loss of unmutated BCR-ABL allele during targeted therapies of CML.	2006 Sep 1	16926302
Dasatinib induces complete hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in blast crisis.	2007 Apr 15	17185463
Nonreceptor tyrosine kinases in prostate cancer.	2007 Feb	17357254
[Innovation of clinical trials for anti-cancer drugs in Japan--proposals from academia with special reference to the development of novel Bcr-Abl/Lyn tyrosine kinase inhibitor INNO-406 (NS-187) for imatinib-resistant chronic myelogenous leukemia].	2007 Feb	17301549
Important therapeutic targets in chronic myelogenous leukemia.	2007 Feb 15	17317816
New targeted therapies for chronic myelogenous leukemia: opportunities to overcome imatinib resistance.	2007 Jan	17292738
Chronic Myeloid Leukaemia in The 21st Century.	2007 Jan	17288299
MK-0457, a novel kinase inhibitor, is active in patients with chronic myeloid leukemia or acute lymphocytic leukemia with the T315I BCR-ABL mutation.	2007 Jan 15	16990603
Dasatinib (BMS-354825) is active in Philadelphia chromosome-positive chronic myelogenous leukemia after imatinib and nilotinib (AMN107) therapy failure.	2007 Jan 15	16990591
L576P KIT mutation in anal melanomas correlates with KIT protein expression and is sensitive to specific kinase inhibition.	2007 Jul 15	17372901
Emerging therapeutic options for Philadelphia-positive acute lymphocytic leukemia.	2007 Mar	17355221
Resistance to dasatinib in Philadelphia-positive leukemia patients and the presence or the selection of mutations at residues 315 and 317 in the BCR-ABL kinase domain.	2007 Mar	17339191
Second-line treatment with dasatinib in patients resistant to imatinib can select novel inhibitor-specific BCR-ABL mutants in Ph+ ALL.	2007 Mar	17329198
In silico profiling of tyrosine kinases binding specificity and drug resistance using Monte Carlo simulations with the ensembles of protein kinase crystal structures.	2007 Mar	17167796
Identification of candidate molecular markers predicting sensitivity in solid tumors to dasatinib: rationale for patient selection.	2007 Mar 1	17332353

Patents

Sample Use Guides

In Vivo Use Guide

The recommended starting dosage of SPRYCEL (dasatinib) for chronic phase CML is 100 mg administered orally once daily. The recommended starting dosage of SPRYCEL for accelerated phase CML, myeloid or lymphoid blast phase CML, or Ph+ ALL is 140 mg administered orally once daily. SPRYCEL can be taken with or without a meal, either in the morning or in the evening.

Route of Administration: Oral

In Vitro Use Guide

Unknown

Substance Class	Chemical Created by `admin` on `Fri Dec 16 20:11:41 UTC 2022` Edited by `admin` on `Fri Dec 16 20:11:41 UTC 2022`
Record UNII	X78UG0A0RN
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

DASATINIB ANHYDROUS

Common Name

English

BMS-354825

Code

English

5-THIAZOLECARBOXAMIDE, N-(2-CHLORO-6-METHYLPHENYL)-2-((6-(4-(2-HYDROXYETHYL)-1-PIPERAZINYL)-2-METHYL-4-PYRIMIDINYL)AMINO)-

Systematic Name

English

dasatinib [INN]

Common Name

English

Dasatinib [WHO-DD]

Common Name

English

DASATINIB [MI]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C155700