DASATINIB

Details

Stereochemistry	ACHIRAL
Molecular Formula	C22H26ClN7O2S.H2O
Molecular Weight	506.021
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

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	H2O
Molecular Weight	18.0153
Charge	0
Count

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

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 8228
Stem cell growth factor receptor 52 Target ID: CHEMBL1936 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17701954	Inhibitor 8228
Ephrin type-A receptor 2 6 Target ID: CHEMBL2068 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17701954	Inhibitor 8228
Platelet-derived growth factor receptor beta 55 Target ID: CHEMBL1913 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17701954	Inhibitor 8228
Tyrosine-protein kinase ABL 29 Target ID: CHEMBL1862 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17701954	Inhibitor 8228

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 8360	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 8360	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 1709 inhibitor 1579 inducer 768	inhibitor 1752 inducer 383	inhibitor 1837 inducer 97	inhibitor 1599

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1509 CYP2A6 704 CYP2B6 799 CYP2C8 901 CYP2C19 1463 CYP2E1 876 CYP3A5 73 P-gp 1437	FMO3 66	CYP2C19 290 CYP1A2 689 CYP2B6 538

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1673	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33, 34	no [IC50 >50 uM]
CYP2B6 985	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33, 34	no [IC50 >50 uM]
CYP2C19 1537	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33, 34	no [IC50 >50 uM]
CYP2D6 1875	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33, 34	no [IC50 >50 uM]
CYP2E1 964	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33, 34	no [IC50 >50 uM]
CYP1A2 1673	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33.0	no
CYP2B6 985	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33.0	no
CYP2C19 1537	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33.0	no
CYP2C9 1803	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33.0	no
CYP2D6 1875	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33.0	no
CYP3A4 1909	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 8, 33	no
P-gp 1626	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 35.0	no
CYP3A4 1909	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 8, 33	weak [Ki 1.9 uM]
CYP2C8 955	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33, 34	yes [IC50 12 uM]
CYP2A6 736	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33, 34	yes [IC50 35 uM]
CYP2C9 1803	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33, 34	yes [IC50 50 uM]
CYP3A5 130	inhibitor 3240 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 66	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 6.0	yes
CYP3A4 1709	substrate 3326 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 1632	inhibitor 1613 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__PharmR.pdf Page: 34.0

PubMed

Title	Date	PubMed
Overriding imatinib resistance with a novel ABL kinase inhibitor.	2004 Jul 16	15256671
Abl inhibitor BMS354825 binding mode in Abelson kinase revealed by molecular docking studies.	2005 Jul	15858616
[Novel inhibitors of Bcr-Abl].	2006	17245319
Dasatinib: BMS 354825.	2006	16542059
[State of the art in the treatment of chronic leukemias].	2006 Apr	16715962
KIT mutations in mastocytosis and their potential as therapeutic targets.	2006 Aug	16931294
Tyrosine kinase inhibitors: the next generation.	2006 Aug	16900596
Dasatinib induces a response in malignant thymoma.	2006 Dec 1	17135636
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
Looking beyond imatinib: next line of targeted drugs for CML shows promise.	2006 Jan 25	16434621
Dasatinib (BMS-354825) selectively induces apoptosis in lung cancer cells dependent on epidermal growth factor receptor signaling for survival.	2006 Jun 1	16740687
Circumventing resistance to kinase-inhibitor therapy.	2006 Jun 15	16775240
Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias.	2006 Jun 15	16775234
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
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
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
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
With targeted drugs, chronic myelogenous leukemia therapy may follow HIV's model.	2007 Feb 7	17284712
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
L576P KIT mutation in anal melanomas correlates with KIT protein expression and is sensitive to specific kinase inhibition.	2007 Jul 15	17372901
Identification and functional signature of genes regulated by structurally different ABL kinase inhibitors.	2007 Jun 14	17213809
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
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
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
MEK1/2 inhibitors sensitize Bcr/Abl+ human leukemia cells to the dual Abl/Src inhibitor BMS-354/825.	2007 May 1	17218385

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 `Wed Jul 05 23:09:44 UTC 2023` Edited by `admin` on `Wed Jul 05 23:09:44 UTC 2023`
Record UNII	RBZ1571X5H
Record Status	`Validated (UNII)`
Record Version

Download

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 [JAN]

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 monohydrate [WHO-DD]

Common Name

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

Created by admin on Wed Jul 05 23:09:45 UTC 2023 , Edited by admin on Wed Jul 05 23:09:45 UTC 2023

FDA ORPHAN DRUG

809221

Created by admin on Wed Jul 05 23:09:45 UTC 2023 , Edited by admin on Wed Jul 05 23:09:45 UTC 2023

EMA ASSESSMENT REPORTS

SPRYCEL (AUTHORIZED: PRECURSOR CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA)

Created by admin on Wed Jul 05 23:09:45 UTC 2023 , Edited by admin on Wed Jul 05 23:09:45 UTC 2023

NCI_THESAURUS

C155700

Created by admin on Wed Jul 05 23:09:45 UTC 2023 , Edited by admin on Wed Jul 05 23:09:45 UTC 2023

NDF-RT

N0000175605

Created by admin on Wed Jul 05 23:09:45 UTC 2023 , Edited by admin on Wed Jul 05 23:09:45 UTC 2023

NCI_THESAURUS

C129825

Created by admin on Wed Jul 05 23:09:45 UTC 2023 , Edited by admin on Wed Jul 05 23:09:45 UTC 2023

EU-Orphan Drug

EU/3/05/338

Created by admin on Wed Jul 05 23:09:45 UTC 2023 , Edited by admin on Wed Jul 05 23:09:45 UTC 2023

WHO-ATC

L01XE06

Created by admin on Wed Jul 05 23:09:45 UTC 2023 , Edited by admin on Wed Jul 05 23:09:45 UTC 2023

FDA ORPHAN DRUG

214605

Created by admin on Wed Jul 05 23:09:45 UTC 2023 , Edited by admin on Wed Jul 05 23:09:45 UTC 2023

FDA ORPHAN DRUG

775320

Created by admin on Wed Jul 05 23:09:45 UTC 2023 , Edited by admin on Wed Jul 05 23:09:45 UTC 2023

FDA ORPHAN DRUG

212405

Created by admin on Wed Jul 05 23:09:45 UTC 2023 , Edited by admin on Wed Jul 05 23:09:45 UTC 2023

NCI_THESAURUS

C1967

Created by admin on Wed Jul 05 23:09:45 UTC 2023 , Edited by admin on Wed Jul 05 23:09:45 UTC 2023

FDA ORPHAN DRUG

750520

Created by admin on Wed Jul 05 23:09:45 UTC 2023 , Edited by admin on Wed Jul 05 23:09:45 UTC 2023

LIVERTOX

NBK548780

Created by admin on Wed Jul 05 23:09:45 UTC 2023 , Edited by admin on Wed Jul 05 23:09:45 UTC 2023

EMA ASSESSMENT REPORTS

SPRYCEL (AUTHORIZED: LEUKEMIA, MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE)

Created by admin on Wed Jul 05 23:09:45 UTC 2023 , Edited by admin on Wed Jul 05 23:09:45 UTC 2023

FDA ORPHAN DRUG

750420

Created by admin on Wed Jul 05 23:09:45 UTC 2023 , Edited by admin on Wed Jul 05 23:09:45 UTC 2023

Code System Code Type Description

FDA UNII

RBZ1571X5H

Created by admin on Wed Jul 05 23:09:45 UTC 2023 , Edited by admin on Wed Jul 05 23:09:45 UTC 2023

PRIMARY

SMS_ID

100000090154

Created by admin on Wed Jul 05 23:09:45 UTC 2023 , Edited by admin on Wed Jul 05 23:09:45 UTC 2023

PRIMARY

DRUG BANK

DB01254

Created by admin on Wed Jul 05 23:09:45 UTC 2023 , Edited by admin on Wed Jul 05 23:09:45 UTC 2023

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DAILYMED

RBZ1571X5H

Created by admin on Wed Jul 05 23:09:45 UTC 2023 , Edited by admin on Wed Jul 05 23:09:45 UTC 2023

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WIKIPEDIA

DASATINIB

Created by admin on Wed Jul 05 23:09:45 UTC 2023 , Edited by admin on Wed Jul 05 23:09:45 UTC 2023

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USAN

SS-39

Created by admin on Wed Jul 05 23:09:45 UTC 2023 , Edited by admin on Wed Jul 05 23:09:45 UTC 2023

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CAS

863127-77-9

Created by admin on Wed Jul 05 23:09:44 UTC 2023 , Edited by admin on Wed Jul 05 23:09:44 UTC 2023

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CHEBI

49375

Created by admin on Wed Jul 05 23:09:45 UTC 2023 , Edited by admin on Wed Jul 05 23:09:45 UTC 2023

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CHEBI

70839

Created by admin on Wed Jul 05 23:09:45 UTC 2023 , Edited by admin on Wed Jul 05 23:09:45 UTC 2023

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ChEMBL

CHEMBL1421

Created by admin on Wed Jul 05 23:09:45 UTC 2023 , Edited by admin on Wed Jul 05 23:09:45 UTC 2023

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DRUG CENTRAL

785

Created by admin on Wed Jul 05 23:09:45 UTC 2023 , Edited by admin on Wed Jul 05 23:09:45 UTC 2023

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LACTMED

Dasatinib

Created by admin on Wed Jul 05 23:09:45 UTC 2023 , Edited by admin on Wed Jul 05 23:09:45 UTC 2023

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IUPHAR

5678

Created by admin on Wed Jul 05 23:09:45 UTC 2023 , Edited by admin on Wed Jul 05 23:09:45 UTC 2023

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MESH

C488369

Created by admin on Wed Jul 05 23:09:45 UTC 2023 , Edited by admin on Wed Jul 05 23:09:45 UTC 2023

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PUBCHEM

11540687

Created by admin on Wed Jul 05 23:09:45 UTC 2023 , Edited by admin on Wed Jul 05 23:09:45 UTC 2023

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EPA CompTox

DTXSID50235486

Created by admin on Wed Jul 05 23:09:45 UTC 2023 , Edited by admin on Wed Jul 05 23:09:45 UTC 2023

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NDF-RT

N0000182141

Created by admin on Wed Jul 05 23:09:45 UTC 2023 , Edited by admin on Wed Jul 05 23:09:45 UTC 2023

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Cytochrome P450 3A4 Inhibitors [MoA]

NCI_THESAURUS

C38713

Created by admin on Wed Jul 05 23:09:45 UTC 2023 , Edited by admin on Wed Jul 05 23:09:45 UTC 2023

PRIMARY

NSC

759877

Created by admin on Wed Jul 05 23:09:45 UTC 2023 , Edited by admin on Wed Jul 05 23:09:45 UTC 2023

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RXCUI

475342

Created by admin on Wed Jul 05 23:09:45 UTC 2023 , Edited by admin on Wed Jul 05 23:09:45 UTC 2023

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RxNorm

EVMPD

SUB23159

Created by admin on Wed Jul 05 23:09:45 UTC 2023 , Edited by admin on Wed Jul 05 23:09:45 UTC 2023

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Related Record Type Details


					VN6AX4RHX4

DASATINIB (S)-PROPYLENE GLYCOLATE

SALT/SOLVATE -> PARENT

Amount:


					908KNZ02WL

ABELSON TYROSINE-PROTEIN KINASE 2

TARGET -> INHIBITOR


					66DDF797LP

OATP-8

TRANSPORTER -> SUBSTRATE


					URP3G75J4S

MITOGEN-ACTIVATED PROTEIN KINASE 14

TARGET -> INHIBITOR


					6D53G0FD0Z

PLASMA PROTEIN FRACTION (HUMAN)

BINDER->LIGAND

Interaction Type:

BINDING

Amount:


					7092WS88L7

PROTO-ONCOGENE TYROSINE-PROTEIN KINASE SRC

TARGET -> INHIBITOR


					X78UG0A0RN

DASATINIB ANHYDROUS

ANHYDROUS->SOLVATE


					R6DUQ1C64H

MITOGEN-ACTIVATED PROTEIN KINASE 11

TARGET -> INHIBITOR


					482M00274D

OCT-2

TRANSPORTER -> INHIBITOR


					QR5SGP5JMT

TYROSINE-PROTEIN KINASE YES

TARGET -> INHIBITOR


					OVI08ABI5H

MAST/STEM CELL GROWTH FACTOR RECEPTOR KIT

TARGET -> INHIBITOR

Interaction Type:

INHIBITOR


					GS7PY5505H

TYROSINE-PROTEIN KINASE ABL1

TARGET -> INHIBITOR


					482M00274D

OCT-2

TRANSPORTER -> SUBSTRATE


					4007E25Z4Z

OCT-3

TRANSPORTER -> INHIBITOR


					ONY583280Z

OCT-1

TRANSPORTER -> SUBSTRATE


					76PXB9FHYD

BCR-ABL KINASE E255K MUTANT (IMATINIB RESISTANT)

TARGET -> INHIBITOR


					RK4TYG2QQ4

DASATINIB PROPYLENE GLYCOLATE

SALT/SOLVATE -> PARENT

Amount:


					1Y8BY3M6Y9

BCR-ABL KINASE

TARGET -> INHIBITOR

Interaction Type:

INHIBITOR


					C1P36E2V4Q

EPHRIN TYPE-B RECEPTOR 2

TARGET -> INHIBITOR


					S276B35HIP

EPHRIN TYPE-A RECEPTOR 8

TARGET -> INHIBITOR


					13U1W2G8EZ

EPHRIN TYPE-A RECEPTOR 3

TARGET -> INHIBITOR


					OCL798DYG0

EPHRIN TYPE-A RECEPTOR 2

TARGET -> INHIBITOR


					4007E25Z4Z

OCT-3

TRANSPORTER -> SUBSTRATE


					X78UG0A0RN

DASATINIB ANHYDROUS

PARENT -> SALT/SOLVATE

Related Record Type Details


					X78UG0A0RN

DASATINIB ANHYDROUS

ACTIVE MOIETY

Name	Property Type	Amount	Referenced Substance	Defining	Parameters	References
Volume of Distribution	PHARMACOKINETIC

Biological Half-life	PHARMACOKINETIC

Details

SMILES

InChI

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

CNS Activity

Originator

Approval Year

Targets

Conditions

Approved Use

Launch Date

Approved Use

Launch Date

Cmax

AUC

T1/2

Funbound

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Tox targets

PubMed

Patents

Sample Use Guides

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

C_max

T_1/2

F_unbound

Drug as perpetrator