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:: 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 3 Target ID: CHEMBL2363074 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17701954	Inhibitor 3315
Stem cell growth factor receptor 20 Target ID: CHEMBL1936 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17701954	Inhibitor 3315
Ephrin type-A receptor 2 5 Target ID: CHEMBL2068 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17701954	Inhibitor 3315
Platelet-derived growth factor receptor beta 25 Target ID: CHEMBL1913 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17701954	Inhibitor 3315
Tyrosine-protein kinase ABL 12 Target ID: CHEMBL1862 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17701954	Inhibitor 3315

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 4033	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 10 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021986s018lbl.pdf	Primary		Approved 4033	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 882 inhibitor 753 inducer 374	inhibitor 825 inducer 191	inhibitor 894 inducer 49	inhibitor 775

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 725 CYP2A6 334 CYP2B6 371 CYP2C8 417 CYP2C19 700 CYP2E1 424 CYP3A5 37 P-gp 666	FMO3 40	CYP2C19 145 CYP1A2 329 CYP2B6 243

Drug as perpetrator

Target	Modality	Activity
CYP1A2 805	inhibitor 1612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33, 34	no [IC50 >50 uM]
CYP2B6 465	inhibitor 1612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33, 34	no [IC50 >50 uM]
CYP2C19 738	inhibitor 1612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33, 34	no [IC50 >50 uM]
CYP2D6 908	inhibitor 1612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33, 34	no [IC50 >50 uM]
CYP2E1 467	inhibitor 1612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33, 34	no [IC50 >50 uM]
CYP1A2 805	inducer 772 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33.0	no
CYP2B6 465	inducer 772 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33.0	no
CYP2C19 738	inducer 772 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33.0	no
CYP2C9 851	inducer 772 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33.0	no
CYP2D6 908	inducer 772 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33.0	no
CYP3A4 920	inducer 772 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 8, 33	no
P-gp 754	inhibitor 1612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 35.0	no
CYP3A4 920	inhibitor 1612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 8, 33	weak [Ki 1.9 uM]
CYP2C8 448	inhibitor 1612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33, 34	yes [IC50 12 uM]
CYP2A6 356	inhibitor 1612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33, 34	yes [IC50 35 uM]
CYP2C9 851	inhibitor 1612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33, 34	yes [IC50 50 uM]
CYP3A5 73	inhibitor 1612 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 40	substrate 1689 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 6.0	yes
CYP3A4 882	substrate 1689 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 796	inhibitor 786 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
Overriding imatinib resistance with a novel ABL kinase inhibitor.	2004 Jul 16	15256671
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
Dasatinib: BMS 354825.	2006	16542059
Glivec and beyond.	2006 Aug	16998957
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), a dual SRC/ABL kinase inhibitor, inhibits the kinase activity of wild-type, juxtamembrane, and activation loop mutant KIT isoforms associated with human malignancies.	2006 Jan 1	16397263
Gateways to clinical trials.	2006 Jul-Aug	16894408
Gateways to clinical trials.	2006 Jun	16845450
Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias.	2006 Jun 15	16775234
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
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
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
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
Dasatinib.	2006 Sep	17001803
Pharmacy benefit spending on oral chemotherapy drugs.	2006 Sep	16981802
Dasatinib in chronic myelogenous leukemia.	2006 Sep 7	16960978
Dasatinib in chronic myelogenous leukemia.	2006 Sep 7	16957155
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
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
BCR-ABL mutant kinetics in CML patients treated with dasatinib.	2007 Jun	17208297
Identification and functional signature of genes regulated by structurally different ABL kinase inhibitors.	2007 Jun 14	17213809
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
MEK1/2 inhibitors sensitize Bcr/Abl+ human leukemia cells to the dual Abl/Src inhibitor BMS-354/825.	2007 May 1	17218385
Dasatinib induces significant hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in accelerated phase.	2007 May 15	17264298
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

In Vitro Use Guide

Unknown

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)`
Record Version

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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