DASATINIB MONOLAURYL SULFATE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C22H26ClN7O2S.C12H26O4S
Molecular Weight	754.403
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of DASATINIB MONOLAURYL SULFATE

Structure Search

SMILES

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

InChI

InChIKey=SWMPKFFMQAIAEW-UHFFFAOYSA-N

InChI=1S/C22H26ClN7O2S.C12H26O4S/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;1-2-3-4-5-6-7-8-9-10-11-12-16-17(13,14)15/h3-5,12-13,31H,6-11H2,1-2H3,(H,28,32)(H,24,25,26,27);2-12H2,1H3,(H,13,14,15)

HIDE SMILES / InChI

Molecular Formula	C12H26O4S
Molecular Weight	266.397
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
[Novel inhibitors of Bcr-Abl].	2006	17245319
[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
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
Gateways to clinical trials.	2006 Jul-Aug	16894408
Gateways to clinical trials.	2006 Jun	16845450
Dasatinib-related alveolar pneumonia responsive to corticosteroids.	2006 Jun	16840219
Panniculitis during dasatinib therapy for imatinib-resistant chronic myelogenous leukemia.	2006 Jun 15	16775249
Circumventing resistance to kinase-inhibitor therapy.	2006 Jun 15	16775240
Clinical development of SRC tyrosine kinase inhibitors in lung cancer.	2006 May	16800962
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
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
The FDA approves new leukemia drug; expands use of current drug.	2006 Nov-Dec	17338066
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
Important therapeutic targets in chronic myelogenous leukemia.	2007 Feb 15	17317816
With targeted drugs, chronic myelogenous leukemia therapy may follow HIV's model.	2007 Feb 7	17284712
Dasatinib.	2007 Jan	17315048
[Molecular targeting therapy for chronic myeloid leukemia].	2007 Jan	17313076
New targeted therapies for chronic myelogenous leukemia: opportunities to overcome imatinib resistance.	2007 Jan	17292738
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 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 `Thu Jul 06 20:58:24 UTC 2023` Edited by `admin` on `Thu Jul 06 20:58:24 UTC 2023`
Record UNII	FY77PS0C4O
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

DASATINIB MONOLAURYL SULFATE

Common Name

English

Dasatinib Laurylsulfate

Official Name

English

DASATINIB LAURYLSULFATE [USAN]

Common Name

English

C078D

Code

English

N-(2-Chloro-6-methylphenyl)-2-({6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl}amino)thiazole-5-carboxamide dodecyl sulfate

Systematic Name

English

Sulfuric acid, monododecyl ester, compd. with N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1-piperazinyl]-2-methyl-4-pyrimidinyl]amino]-5-thiazolecarboxamide (1:1)

Systematic Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

888722