Dasatinib Laurylsulfate

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 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

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 8297
Stem cell growth factor receptor 53 Target ID: CHEMBL1936 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17701954	Inhibitor 8297
Ephrin type-A receptor 2 6 Target ID: CHEMBL2068 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17701954	Inhibitor 8297
Platelet-derived growth factor receptor beta 56 Target ID: CHEMBL1913 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17701954	Inhibitor 8297
Tyrosine-protein kinase ABL 29 Target ID: CHEMBL1862 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17701954	Inhibitor 8297

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 8429	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 2006
Acute lymphoblastic leukemia 27 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021986s018lbl.pdf	Primary		Approved 8429	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 2006

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 1737 inhibitor 1587 inducer 781	inhibitor 1767 inducer 389	inhibitor 1852 inducer 97	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2A6 707 CYP2B6 810 CYP2C8 911 CYP2C19 1478 CYP2E1 882 CYP3A5 73 P-gp 1461	FMO3 67	CYP2C19 293 CYP1A2 701 CYP2B6 547

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33, 34	no [IC50 >50 uM]
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33, 34	no [IC50 >50 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33, 34	no [IC50 >50 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33, 34	no [IC50 >50 uM]
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33, 34	no [IC50 >50 uM]
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33.0	no
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33.0	no
CYP2C19 1553	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33.0	no
CYP2C9 1819	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33.0	no
CYP2D6 1891	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33.0	no
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 8, 33	no
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 35.0	no
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 8, 33	weak [Ki 1.9 uM]
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33, 34	yes [IC50 12 uM]
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33, 34	yes [IC50 35 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 33, 34	yes [IC50 50 uM]
CYP3A5 130	inhibitor 3277 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 67	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf Page: 6.0	yes
CYP3A4 1737	substrate 3367 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 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__PharmR.pdf Page: 34.0

PubMed

Title	Date	PubMed
In vitro activity of Bcr-Abl inhibitors AMN107 and BMS-354825 against clinically relevant imatinib-resistant Abl kinase domain mutants.	2005 Jun 1	15930265
Chronic myelogenous leukemia.	2005 Oct	16235580
[Novel inhibitors of Bcr-Abl].	2006	17245319
[Some new findings in the pathogenesis of myeloproliferative disorders and new insight into more effective treatment].	2006	16468234
[New strategies to overcome imatinib resistance in treatment for chronic myelocytic leukemia].	2006 Aug	17236546
Glivec and beyond.	2006 Aug	16998957
KIT mutations in mastocytosis and their potential as therapeutic targets.	2006 Aug	16931294
Tyrosine kinase inhibitors: the next generation.	2006 Aug	16900596
Leukemogenesis induced by wild-type and STI571-resistant BCR/ABL is potently suppressed by C/EBPalpha.	2006 Aug 15	16670262
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
Structure of the kinase domain of an imatinib-resistant Abl mutant in complex with the Aurora kinase inhibitor VX-680.	2006 Jan 15	16424036
Dasatinib-related alveolar pneumonia responsive to corticosteroids.	2006 Jun	16840219
Dasatinib (BMS-354825) targets an earlier progenitor population than imatinib in primary CML but does not eliminate the quiescent fraction.	2006 Jun 1	16469872
Clinical development of SRC tyrosine kinase inhibitors in lung cancer.	2006 May	16800962
The second generation of BCR-ABL tyrosine kinase inhibitors.	2006 May	16757427
New assignments for multitasking signal transduction inhibitors.	2006 May	16497876
Potent inhibition of platelet-derived growth factor-induced responses in vascular smooth muscle cells by BMS-354825 (dasatinib).	2006 May	16436588
Novel tyrosine kinase inhibitors in chronic myelogenous leukemia.	2006 Nov	16988578
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
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
Nonreceptor tyrosine kinases in prostate cancer.	2007 Feb	17357254
[Innovation of clinical trials for anti-cancer drugs in Japan--proposals from academia with special reference to the development of novel Bcr-Abl/Lyn tyrosine kinase inhibitor INNO-406 (NS-187) for imatinib-resistant chronic myelogenous leukemia].	2007 Feb	17301549
Important therapeutic targets in chronic myelogenous leukemia.	2007 Feb 15	17317816
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
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
L576P KIT mutation in anal melanomas correlates with KIT protein expression and is sensitive to specific kinase inhibition.	2007 Jul 15	17372901
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
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 induces significant hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in accelerated phase.	2007 May 15	17264298
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

In Vitro Use Guide

Unknown

Name

Type

Language

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

DASATINIB MONOLAURYL SULFATE

Common 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