DASATINIB

Details

Stereochemistry	ACHIRAL
Molecular Formula	C22H26ClN7O2S.H2O
Molecular Weight	506.0227
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cc1cccc(c1N=C(c2cnc(Nc3cc(nc(C)n3)N4CCN(CC4)CCO)s2)O)Cl.O

InChI

InChIKey=XHXFZZNHDVTMLI-UHFFFAOYSA-N

InChI=1S/C22H26ClN7O2S.H2O/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);1H2

HIDE SMILES / InChI

Molecular Formula	C22H26ClN7O2S
Molecular Weight	488.0074
Charge	0
Count

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

Molecular Formula	H2O
Molecular Weight	18.0153
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:: 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
SRC 5 Target ID: CHEMBL2363074 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17701954	Inhibitor 7701	Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML)
Stem cell growth factor receptor 47 Target ID: CHEMBL1936 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17701954	Inhibitor 7701	Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML)
Ephrin type-A receptor 2 6 Target ID: CHEMBL2068 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17701954	Inhibitor 7701	Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML)
Platelet-derived growth factor receptor beta 51 Target ID: CHEMBL1913 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17701954	Inhibitor 7701	Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML)
Tyrosine-protein kinase ABL 26 Target ID: CHEMBL1862 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17701954	Inhibitor 7701	Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML)

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	Tyrosine-protein kinase ABL SRC Stem cell growth factor receptor Ephrin type-A receptor 2 Platelet-derived growth factor receptor beta	Approved 7997	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 1151452800000
Acute lymphoblastic leukemia 24 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021986s018lbl.pdf	Primary		Approved 7997	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 1151452800000

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/	unhealthy, 32-81 years Health Status: unhealthy Age Group: 32-81 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/19789325/	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/
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/	unhealthy, 32-81 years Health Status: unhealthy Age Group: 32-81 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/19789325/	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/
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/	unhealthy, 32-81 years Health Status: unhealthy Age Group: 32-81 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/19789325/	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/
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/	unhealthy, 32-81 years Health Status: unhealthy Age Group: 32-81 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/19789325/	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/
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/	unhealthy, 32-81 years Health Status: unhealthy Age Group: 32-81 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/19789325/	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/
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/	unhealthy, 32-81 years Health Status: unhealthy Age Group: 32-81 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/19789325/	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/
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/	unhealthy, 32-81 years Health Status: unhealthy Age Group: 32-81 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/19789325/	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/
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/	unhealthy, 32-81 years Health Status: unhealthy Age Group: 32-81 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/19789325/	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/
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/	unhealthy, 32-81 years Health Status: unhealthy Age Group: 32-81 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/19789325/	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/
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/	unhealthy, 32-81 years Health Status: unhealthy Age Group: 32-81 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/19789325/	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/
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/	unhealthy, 32-81 years Health Status: unhealthy Age Group: 32-81 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/19789325/	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/
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/	unhealthy, 32-81 years Health Status: unhealthy Age Group: 32-81 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/19789325/	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/

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1470 inhibitor 1172 inducer 657	inhibitor 1318 inducer 343	inhibitor 1421 inducer 93	inhibitor 1360

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1268 CYP2A6 594 CYP2B6 679 CYP2C8 761 CYP2C19 1215 CYP2E1 761 CYP3A5 66 P-gp 1089	FMO3 49	CYP2C19 260 CYP1A2 618 CYP2B6 486

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1406	inhibitor 2614 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33, 34	no [IC50 >50 uM]
CYP2B6 845	inhibitor 2614 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33, 34	no [IC50 >50 uM]
CYP2C19 1277	inhibitor 2614 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33, 34	no [IC50 >50 uM]
CYP2D6 1455	inhibitor 2614 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33, 34	no [IC50 >50 uM]
CYP2E1 841	inhibitor 2614 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33, 34	no [IC50 >50 uM]
CYP1A2 1406	inducer 1333 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33	no
CYP2B6 845	inducer 1333 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33	no
CYP2C19 1277	inducer 1333 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33	no
CYP2C9 1362	inducer 1333 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33	no
CYP2D6 1455	inducer 1333 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33	no
CYP3A4 1462	inducer 1333 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 8, 33	no
P-gp 1255	inhibitor 2614 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 35	no
CYP3A4 1462	inhibitor 2614 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 8, 33	weak [Ki 1.9 uM]
CYP2C8 810	inhibitor 2614 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33, 34	yes [IC50 12 uM]
CYP2A6 625	inhibitor 2614 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33, 34	yes [IC50 35 uM]
CYP2C9 1362	inhibitor 2614 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33, 34	yes [IC50 50 uM]
CYP3A5 119	inhibitor 2614 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33	yes

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
FMO3 49	substrate 2752 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 6	yes
CYP3A4 1470	substrate 2752 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 1392	inhibitor 1374 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__PharmR.pdf Page: 34

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	NO19372
1PlusChem LLC	1P00300B
1PlusChem LLC	1P0032NV
A2B Chem	AB39179
A2B Chem	AB42619
AA Blocks	AA002ZGV
ACT Chemical	ACT11719
AChemBlock	10489
AK Scientific	J10239
AK Scientific	J93088
AK Scientific	S104
AK Scientific	Z1754
AOBIOUS INC	AOB87355
APExBIO	A3017
APExBIO	B5954
AbovChem LLC	HY-10181
AbovChem LLC	HY-10181A
AlchemyPharm	AP10018
AlchemyPharm	AP10019
Alfa Chemistry	ACM863127779
Ambeed	A210354
Ambeed	A355193
Apollo Scientific	OR302638
Asinex	LAS31066578
AstaTech	62242
AstaTech	C10466
Axon MedChem	1392
BLDpharm	BD213871
BLDpharm	BD630906
BOC Sciences	1132093-70-9
BOC Sciences	302962-49-8
BOC Sciences	863127-77-9
Bide Pharmatech	BD213871
Bide Pharmatech	BD35158
BioSynth	Q-101345
BlocksMatrix Scientific	75512
BlocksMatrix Scientific	94785
Bosche Scientific	D12642
Capot Chemical	27415
Cayman Chemical	11498
Chem Scene	CS-0100
Chem Scene	CS-1585
ChemShuttle	101030
ChemShuttle	112867
Combi-Blocks	QA-3341
Combi-Blocks	ST-7591
Compound Cloud	11540687
Compound Cloud	3062316
Enamine	EN300-123025
Enamine	Z2786158251
Excenen	EX-A401
Exclusive Chemistry	2122
Frontier Scientific Services	500055738
Hairui	HR126384
Hairui	HR23836
Hangzhou APIChem Technology	AC-22749
Hangzhou Yuhao Chemical Technology	LX2535
Hangzhou Yuhao Chemical Technology	YH53013
Hangzhou Yuhao Chemical Technology	YH90453
KeyOrganics	GS-4248
KeyOrganics	GS-6548
Lab Seeker	SC-22079
Lan Pharmatech	LQT-B40304
MedChem Express	HY-10181
MedChem Express	HY-10181A
MolPort	MolPort-003-846-143
MolPort	MolPort-009-198-935
MolPort	MolPort-046-416-821
Molcore	CS19372
Molnova	M13952
Molnova	M16201
Molnova	M16248
MuseChem	A000113
MuseChem	A000288
Nanjing Pope Bio-tech	NSTH-D29628
Norris Pharm	NSTH-D29628
Norris Pharm	NSZB-A245338
PI Chemicals	PI-33797
PI Chemicals	PI-37460
Ryan Scientific	Tetracycline
Selleck Chemicals	S1021
Selleck Chemicals	S5254
Selleck Chemicals	S7782
ShangHai Biochempartner	BCP000111
ShangHai Biochempartner	BCP01797
ShangHai Biochempartner	BCP09727
Sigma Aldrich	CDS023389
Sigma Aldrich	CDS023389\|ALDRICH
StruChem	SC-22079
SynQuest	103142
SynQuest	8H48-5-73
TargetMol	T1448
TargetMol	T1448L
Tetrahedron	TS93663
Tetrahedron	TS94176
Toronto Research Chemicals	D193600
W&J PharmaChem	50C1020809
Wonderchem	WD0753U
ZINC	ZINC000003986735	http://zinc15.docking.org/substances/ZINC000003986735
eMolecules	10748986
eMolecules	27528318
eMolecules	50282569
eNovation Chemicals	D486019
eNovation Chemicals	D580660
eNovation Chemicals	K09853
mcule	MCULE-2013135265
mcule	MCULE-3234957185

PubMed

Title	Date	PubMed
[Tyrosine kinase inhibitors in the therapy of chronic myeloid leukaemia].	2006	17013368
[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
Targeting ABL and SRC kinases in chronic myeloid leukemia: experience with dasatinib.	2006 Dec	17155893
Identification of potential biomarkers for measuring inhibition of Src kinase activity in colon cancer cells following treatment with dasatinib.	2006 Dec	17148760
Dasatinib (BMS-354825) pharmacokinetics and pharmacodynamic biomarkers in animal models predict optimal clinical exposure.	2006 Dec 1	17145844
Dasatinib induces a response in malignant thymoma.	2006 Dec 1	17135636
In vitro and in vivo activity of SKI-606, a novel Src-Abl inhibitor, against imatinib-resistant Bcr-Abl+ neoplastic cells.	2006 Dec 1	17114238
Novel treatment strategies for chronic myeloid leukemia.	2006 Dec 1	17106016
Molecular pathogenesis and therapy of polycythemia induced in mice by JAK2 V617F.	2006 Dec 20	17183644
Dasatinib-related alveolar pneumonia responsive to corticosteroids.	2006 Jun	16840219
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
Presence or the emergence of a F317L BCR-ABL mutation may be associated with resistance to dasatinib in Philadelphia chromosome-positive leukemia.	2006 Nov 20	17114651
BCR and its mutants, the reciprocal t(9;22)-associated ABL/BCR fusion proteins, differentially regulate the cytoskeleton and cell motility.	2006 Nov 7	17090304
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
Pharmacy benefit spending on oral chemotherapy drugs.	2006 Sep	16981802
Sequential emergence of ABL-kinase mutations with loss of unmutated BCR-ABL allele during targeted therapies of CML.	2006 Sep 1	16926302
Dasatinib in chronic myelogenous leukemia.	2006 Sep 7	16960978
Dasatinib in chronic myelogenous leukemia.	2006 Sep 7	16957155
Outcome of patients with Philadelphia chromosome-positive chronic myelogenous leukemia post-imatinib mesylate failure.	2007 Apr 15	17342766
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
With targeted drugs, chronic myelogenous leukemia therapy may follow HIV's model.	2007 Feb 7	17284712
Dasatinib.	2007 Jan	17315048
Chronic Myeloid Leukaemia in The 21st Century.	2007 Jan	17288299
Dasatinib (Sprycel) for CML and Ph + ALL.	2007 Jan 15	17220814
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
BCR-ABL mutant kinetics in CML patients treated with dasatinib.	2007 Jun	17208297
Dasatinib or high-dose imatinib for chronic-phase chronic myeloid leukemia after failure of first-line imatinib: a randomized phase 2 trial.	2007 Jun 15	17317857
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
Dasatinib inhibits migration and invasion in diverse human sarcoma cell lines and induces apoptosis in bone sarcoma cells dependent on SRC kinase for survival.	2007 Mar 15	17363602
Dasatinib induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapy.	2007 Mar 15	17138817
Dasatinib, an orally active small molecule inhibitor of both the src and abl kinases, selectively inhibits growth of basal-type/"triple-negative" breast cancer cell lines growing in vitro.	2007 Nov	17268817
Dasatinib may also inhibit c-Kit in triple negative breast cancer cell lines.	2008 Jan	17351742

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

Substance Class	Chemical Created by `admin` on `Fri Jun 25 21:58:19 UTC 2021` Edited by `admin` on `Fri Jun 25 21:58:19 UTC 2021`
Record UNII	RBZ1571X5H
Record Status	`Validated (UNII)`
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Name

Type

Language

DASATINIB

Official Name

English

DASATINIB MONOHYDRATE

Common Name

English

BMS-354825 HYDRATE

Code

English

SPRYCEL

Brand Name

English

N-(2-CHLORO-6-METHYLPHENYL)-2-((6-(4-(2-HYDROXYETHYL)PIPERAZIN-1-YL)-2-METHYLPYRIMIDIN-4-YL)AMINO)THIAZOLE-5-CARBOXAMIDE HYDRATE

Systematic Name

English

DASATINIB HYDRATE

Common Name

English

DASATINIB MONOHYDRATE [WHO-DD]

Common Name

English

DASATINIB [ORANGE BOOK]

Common Name

English

DASATINIB [VANDF]

Common Name

English

DASATINIB [EMA EPAR]

Common Name

English

NSC-759877

Code

English

DASATINIB [USAN]

Common Name

English

DASATINIB HYDRATE [JAN]

Common Name

English

BMS-354825-03

Code

English

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

Systematic Name

English

Classification Tree Code System Code

WHO-VATC

QL01XE06