Pharmacogenomics. Knowledge. Implementation.

Chemical: Drug
dasatinib

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Prescribing Info (0) Drug Labels (4) Clinical Annotations (5)

PharmGKB contains no prescribing info for this . Contact us to report known genotype-based dosing guidelines, or if you are interested in developing guidelines.

Annotated Labels

Annotation of FDA Label for dasatinib and ABL1,BCR
Annotation of EMA Label for dasatinib and ABL1,BCR
Annotation of PMDA Label for dasatinib and ABL1,BCR
Annotation of HCSC Label for dasatinib and ABI1,BCR

last updated 10/25/2013

1. Annotation of FDA Label for dasatinib and ABL1,BCR

On FDA Biomarker List

Testing required

Summary

The FDA-approved drug label for dasatinib (SPRYCEL) notes that it is intended for adults with Philadelphia chromosome-positive chronic myeloid leukemia (CML) or acute lymphoblastic leukemia (Ph+ ALL) and resistance or intolerance to prior therapy.

There's more of this label. Read more.

last updated 10/25/2013

2. Annotation of EMA Label for dasatinib and ABL1,BCR

Testing required

Summary

The EMA European Public Assessment Report (EPAR) highlights information regarding the indication of Dasatinib (Sprycel) in patients with Philadelphia chromosome positive (Ph+) chronic myelogenous leukaemia or acute lymphoblastic leukaemia.

There's more of this label. Read more.

3. Annotation of PMDA Label for dasatinib and ABL1,BCR

Testing required

Summary

The PMDA package insert for dasatinib states that it is indicated for individuals with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL).

There's more of this label. Read more.

4. Annotation of HCSC Label for dasatinib and ABI1,BCR

Testing required

Summary

The product monograph for dasatinib (SPRYCEL) states that it is indicated for the treatment of adults with Philadelphia chromosome positive (Ph+) chronic myeloid leukemia.

There's more of this label. Read more.

PharmGKB contains no Clinical Variants that meet the highest level of criteria.

To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the page.

Clinical Annotation for rs45605536 (ABCG2), dasatinib and imatinib (level 4)

Level of Evidence: Level 4
Type: Other
Variant: rs45605536
Genes: ABCG2
OMB Race: Unknown
Race Notes: in-vitro

To see the rest of this clinical annotation please register or sign in.

Clinical Annotation for rs58818712 (ABCG2), dasatinib and imatinib (level 4)

Level of Evidence: Level 4
Type: Other
Variant: rs58818712
Genes: ABCG2
OMB Race: Unknown
Race Notes: in-vitro

To see the rest of this clinical annotation please register or sign in.

Clinical Annotation for rs41282401 (ABCG2), dasatinib, imatinib and nilotinib (level 4)

Level of Evidence: Level 4
Type: Other
Variant: rs41282401
Genes: ABCG2
OMB Race: Unknown
Race Notes: in-vitro

To see the rest of this clinical annotation please register or sign in.

Clinical Annotation for rs1061018 (ABCG2), dasatinib, imatinib and nilotinib (level 4)

Level of Evidence: Level 4
Type: Other
Variant: rs1061018
Genes: ABCG2
OMB Race: Unknown
Race Notes: in-vitro

To see the rest of this clinical annotation please register or sign in.

Clinical Annotation for rs2231137 (ABCG2), dasatinib, imatinib and nilotinib (level 4)

Level of Evidence: Level 4
Type: Other
Variant: rs2231137
Genes: ABCG2
OMB Race: Unknown
Race Notes: in-vitro

To see the rest of this clinical annotation please register or sign in.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

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The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page.

Links in the "Gene" column lead to PharmGKB Gene Pages.

List of all variant annotations for dasatinib

	Gene ?	Variant? (147)	Alternate Names ?	Chemicals ?	Alleles ? (+ chr strand)	Function ?	Amino Acid? Translation
CA VA	ABCG2	rs1061018	NC_000004.11:g.89042853A>G, NC_000004.12:g.88121701A>G, NG_032067.2:g.114622T>C, NM_001257386.1:c.623T>C, NM_004827.2:c.623T>C, NP_001244315.1:p.Phe208Ser, NP_004818.2:p.Phe208Ser, XM_005263354.1:c.623T>C, XM_005263354.2:c.623T>C, XM_005263355.1:c.623T>C, XM_005263355.2:c.623T>C, XM_005263356.1:c.623T>C, XM_005263356.2:c.623T>C, XM_011532420.1:c.623T>C, XP_005263411.1:p.Phe208Ser, XP_005263412.1:p.Phe208Ser, XP_005263413.1:p.Phe208Ser, XP_011530722.1:p.Phe208Ser, rs386514545	nilotinib dasatinib imatinib	A > G	SNP	F208S
VA	ABL1	rs121913459	NC_000009.11:g.133748283C>T, NC_000009.12:g.130872896C>T, NG_012034.1:g.164016C>T, NM_005157.5:c.944C>T, NM_007313.2:c.1001C>T, NP_005148.2:p.Thr315Ile, NP_009297.2:p.Thr334Ile, XM_005272177.1:c.998C>T, XP_005272234.1:p.Thr333Ile	dasatinib	C > T	SNP	T315I
CA VA	ABCG2	rs2231137	NC_000004.11:g.89061114C>T, NC_000004.12:g.88139962C>T, NG_032067.2:g.96361G>A, NM_001257386.1:c.34G>A, NM_004827.2:c.34G>A, NP_001244315.1:p.Val12Met, NP_004818.2:p.Val12Met, XM_005263354.1:c.34G>A, XM_005263354.2:c.34G>A, XM_005263355.1:c.34G>A, XM_005263355.2:c.34G>A, XM_005263356.1:c.34G>A, XM_005263356.2:c.34G>A, XM_011532420.1:c.34G>A, XP_005263411.1:p.Val12Met, XP_005263412.1:p.Val12Met, XP_005263413.1:p.Val12Met, XP_011530722.1:p.Val12Met	nilotinib dasatinib imatinib	C > T	SNP	V12M
VA	ABCG2	rs2231142	NC_000004.11:g.89052323G>T, NC_000004.12:g.88131171G>T, NG_032067.2:g.105152C>A, NM_001257386.1:c.421C>A, NM_004827.2:c.421C>A, NP_001244315.1:p.Gln141Lys, NP_004818.2:p.Gln141Lys, XM_005263354.1:c.421C>A, XM_005263354.2:c.421C>A, XM_005263355.1:c.421C>A, XM_005263355.2:c.421C>A, XM_005263356.1:c.421C>A, XM_005263356.2:c.421C>A, XM_011532420.1:c.421C>A, XP_005263411.1:p.Gln141Lys, XP_005263412.1:p.Gln141Lys, XP_005263413.1:p.Gln141Lys, XP_011530722.1:p.Gln141Lys, rs12721641, rs28365035, rs3736117, rs52809243, rs58973676	nilotinib dasatinib imatinib	G > T	SNP	Q141K
CA VA	ABCG2	rs41282401	NC_000004.11:g.89036166C>G, NC_000004.12:g.88115014C>G, NG_032067.2:g.121309G>C, NM_001257386.1:c.886G>C, NM_004827.2:c.886G>C, NP_001244315.1:p.Asp296His, NP_004818.2:p.Asp296His, XM_005263354.1:c.886G>C, XM_005263354.2:c.886G>C, XM_005263355.1:c.886G>C, XM_005263355.2:c.886G>C, XM_005263356.1:c.886G>C, XM_005263356.2:c.886G>C, XM_011532420.1:c.886G>C, XP_005263411.1:p.Asp296His, XP_005263412.1:p.Asp296His, XP_005263413.1:p.Asp296His, XP_011530722.1:p.Asp296His	nilotinib dasatinib imatinib	C > G	SNP	D296H
CA VA	ABCG2	rs45605536	NC_000004.11:g.89018670C>T, NC_000004.12:g.88097518C>T, NG_032067.2:g.138805G>A, NM_001257386.1:c.1582G>A, NM_004827.2:c.1582G>A, NP_001244315.1:p.Ala528Thr, NP_004818.2:p.Ala528Thr, XM_005263354.1:c.1582G>A, XM_005263354.2:c.1582G>A, XM_005263355.1:c.1582G>A, XM_005263355.2:c.1582G>A, XM_005263356.1:c.1576G>A, XM_005263356.2:c.1576G>A, XM_011532420.1:c.1582G>A, XP_005263411.1:p.Ala528Thr, XP_005263412.1:p.Ala528Thr, XP_005263413.1:p.Ala526Thr, XP_011530722.1:p.Ala528Thr	dasatinib imatinib	C > T	SNP	A528T
CA VA	ABCG2	rs58818712	NC_000004.11:g.89018678A>C, NC_000004.12:g.88097526A>C, NG_032067.2:g.138797T>G, NM_001257386.1:c.1574T>G, NM_004827.2:c.1574T>G, NP_001244315.1:p.Leu525Arg, NP_004818.2:p.Leu525Arg, XM_005263354.1:c.1574T>G, XM_005263354.2:c.1574T>G, XM_005263355.1:c.1574T>G, XM_005263355.2:c.1574T>G, XM_005263356.1:c.1568T>G, XM_005263356.2:c.1568T>G, XM_011532420.1:c.1574T>G, XP_005263411.1:p.Leu525Arg, XP_005263412.1:p.Leu525Arg, XP_005263413.1:p.Leu523Arg, XP_011530722.1:p.Leu525Arg, rs61735384	nilotinib dasatinib imatinib	A > C	SNP	L525R

Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 147

2D structure from PubChem

[ see larger image ] [ see 3D structure ]

provided by PubChem

Overview

Generic Names

BMS-354825
dasatinib

Trade Names

Sprycel

Brand Mixture Names

PharmGKB Accession Id

PA162372878

Type(s):

Drug

Metabolite(s):

Description

Dasatinib is an oral dual BCR/ABL and Src family tyrosine kinase inhibitor approved for use in patients with chronic myelogenous leukemia (CML). The main targets of Dasatinib, are BCRABL, SRC, Ephrins and GFR.

Source: Drug Bank

Indication

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.

Source: Drug Bank

Other Vocabularies

MeSH: dasatinib (C488369)
ATC: Protein kinase inhibitors (L01XE)
UMLS: dasatinib (C1455147)
RxNorm: dasatinib (475342)
NDFRT: DASATINIB (N0000176043)

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

Dasatinib, at nanomolar concentrations, inhibits the following kinases: BCR-ABL, SRC family (SRC, LCK, YES, FYN), c-KIT, EPHA2, and PDGFRbeta. Based on modeling studies, dasatinib is predicted to bind to multiple conformations of the ABL kinase. In vitro, dasatinib was active in leukemic cell lines representing variants of imatinib mesylate sensitive and resistant disease. Dasatinib inhibited the growth of chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL) cell lines overexpressing BCR-ABL. Under the conditions of the assays, dasatinib was able to overcome imatinib resistance resulting from BCR-ABL kinase domain mutations, activation of alternate signaling pathways involving the SRC family kinases (LYN, HCK), and multi-drug resistance gene overexpression.

Source: Drug Bank

Pharmacology

Dasatinib is an oral dual BCR/ABL and Src family tyrosine kinase inhibitor

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Dasatinib is extensively metabolized in humans, primarily by the cytochrome P450 enzyme 3A4

Source: Drug Bank

Protein Binding

96%

Source: Drug Bank

Half-Life

The overall mean terminal half-life of dasatinib is 3-5 hours.

Source: Drug Bank

Toxicity

Acute overdose in animals was associated with cardiotoxicity.

Source: Drug Bank

Route of Elimination

Dasatinib is extensively metabolized in humans, primarily by the cytochrome P450 enzyme 3A4. Elimination is primarily via the feces.

Source: Drug Bank

Volume of Distribution

* 2505 L

Source: Drug Bank

Chemical Properties

Chemical Formula

C22H26ClN7O2S

Source: Drug Bank

Isomeric SMILES

Cc1cccc(c1NC(=O)c2cnc(s2)Nc3cc(nc(n3)C)N4CCN(CC4)CCO)Cl

Source: OpenEye

Canonical SMILES

CC1=NC(NC2=NC=C(S2)C(=O)NC2=C(C)C=CC=C2Cl)=CC(=N1)N1CCN(CCO)CC1

Source: Drug Bank

Average Molecular Weight

488.006

Source: Drug Bank

Monoisotopic Molecular Weight

487.155721508

Source: Drug Bank

SMILES

CC1=NC(NC2=NC=C(S2)C(=O)NC2=C(C)C=CC=C2Cl)=CC(=N1)N1CCN(CCO)CC1

Source: Drug Bank

InChI String

InChI=1S/C22H26ClN7O2S/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)

Source: Drug Bank

Related Genes and Targets Related Drugs and Interactions Related Diseases/Phenotypes

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Curated Information ?

Evidence	Gene
CA VA	ABCG2
DL	ABI1
DL VA VIP	ABL1
DL	BCR
DL	CYP1A2
DL	CYP2A6
DL	CYP2B6
DL	CYP2C19
DL	CYP2C8
DL	CYP2C9
DL	CYP2D6
DL	CYP2E1
DL	CYP3A4
DL	FMO3

Drug Targets

Gene	Description
ABL1	(source: Drug Bank )
ABL2	(source: Drug Bank )
EPHA2	(source: Drug Bank )
FYN	(source: Drug Bank )
KIT	(source: Drug Bank )
LCK	(source: Drug Bank )
PDGFRB	(source: Drug Bank )
SRC	(source: Drug Bank )
STAT5B	(source: Drug Bank )
YES1	(source: Drug Bank )

Curated Information ?

Evidence	Drug
	esomeprazole

Drug Interactions

Interaction	Description
omeprazole - dasatinib	Possible decreased levels of dasatinib (source: Drug Bank )
omeprazole - dasatinib	Omeprazole may decrease the serum level of dasatinib. (source: Drug Bank )
pantoprazole - dasatinib	Possible decreased levels of dasatinib (source: Drug Bank )
pantoprazole - dasatinib	Pantoprazole may decrease the serum level of dasatinib. (source: Drug Bank )
phenobarbital - dasatinib	Decreased levels/efficacy of ddasatinib (source: Drug Bank )
phenobarbital - dasatinib	Phenobarbital may decrease the serum level and efficacy of dasatinib. (source: Drug Bank )
phenytoin - dasatinib	Decreased levels/efficacy of dasatinib (source: Drug Bank )
phenytoin - dasatinib	Phenytoin may decrease the serum level and efficacy of dasatinib. (source: Drug Bank )
rabeprazole - dasatinib	Possible decreased levels of dasatinib (source: Drug Bank )
rabeprazole - dasatinib	Rabeprazole may decrease the serum level of dasatinib. (source: Drug Bank )
ranitidine - dasatinib	Possible decreased levels of dasatinib (source: Drug Bank )
ranitidine - dasatinib	Ranitidine may decrease the serum level of dasatinib. (source: Drug Bank )
rifampin - dasatinib	Decreased levels/efficacy of dasatinib (source: Drug Bank )
rifampin - dasatinib	Rifampin may decrease the serum level and efficacy of dasatinib. (source: Drug Bank )
telithromycin - dasatinib	Increased levels/toxicity of dasatinib (source: Drug Bank )
telithromycin - dasatinib	Telithromycin may reduce clearance of Dasatinib. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Dasatinib if Telithromycin is initiated, discontinued or dose changed. (source: Drug Bank )
thiothixene - dasatinib	May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration. (source: Drug Bank )
thiothixene - dasatinib	May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration. (source: Drug Bank )
toremifene - dasatinib	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration. (source: Drug Bank )
trimipramine - dasatinib	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution. (source: Drug Bank )
voriconazole - dasatinib	Additive QTc prolongation may occur. Voriconazole, a strong CYP3A4 inhibitor, may also increase the serum concentration of dasatinib by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of dasatinib if voriconazole is initiated, discontinued or dose changed. (source: Drug Bank )
vorinostat - dasatinib	Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP). (source: Drug Bank )
ziprasidone - dasatinib	Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated. (source: Drug Bank )
zuclopenthixol - dasatinib	Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP). (source: Drug Bank )

Curated Information ?

Evidence	Disease
VA	Leukemia
DL	Neoplasms
VA	Recurrence

Publications related to dasatinib: 19

	Effect of esomeprazole on the oral absorption of dasatinib in a patient with Philadelphia-positive acute lymphoblastic leukemia. British journal of clinical pharmacology. 2016. Pape Elise, et al.
	Childhood Acute Lymphoblastic Leukemia: Progress Through Collaboration. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2015. Pui Ching-Hon, et al.
	Eradication of T315I mutation in chronic myeloid leukemia without third-generation tyrosine kinase inhibitor: a case report. Pharmacogenomics. 2015. Venton Geoffroy, et al.
VIP	BCR-ABL1 compound mutations combining key kinase domain positions confer clinical resistance to ponatinib in Ph chromosome-positive leukemia. Cancer cell. 2014. Zabriskie Matthew S, et al.
	In vitro assessment of time-dependent inhibitory effects on CYP2C8 and CYP3A activity by fourteen protein kinase inhibitors. Drug metabolism and disposition: the biological fate of chemicals. 2014. Filppula Anne M, et al.
	Interaction of the Efflux Transporters ABCB1 and ABCG2 With Imatinib, Nilotinib, and Dasatinib. Clinical pharmacology and therapeutics. 2014. Eadie L N, et al.
	EMA Initiatives and Perspectives on Pharmacogenomics. British journal of clinical pharmacology. 2014. Ehmann Falk, et al.
CA VA	Single-nucleotide polymorphisms of ABCG2 increase the efficacy of tyrosine kinase inhibitors in the K562 chronic myeloid leukemia cell line. Pharmacogenetics and genomics. 2014. Skoglund Karin, et al.
	Phase 2 study of subcutaneous omacetaxine mepesuccinate for chronic-phase chronic myeloid leukemia patients resistant to or intolerant of tyrosine kinase inhibitors. American journal of hematology. 2013. Cortes J, et al.
	Challenges in pharmacogenetics. European journal of clinical pharmacology. 2013. Cascorbi Ingolf, et al.
	Pharmacogenomics as a risk mitigation strategy for chemotherapeutic cardiotoxicity. Pharmacogenomics. 2013. Jensen Brian C, et al.
	Off-target effects of BCR-ABL1 inhibitors and their potential long-term implications in patients with chronic myeloid leukemia. Leukemia & lymphoma. 2012. Steegmann Juan Luis, et al.
	Novel aspects of therapy with the dual Src and Abl kinase inhibitor bosutinib in chronic myeloid leukemia. Expert review of anticancer therapy. 2012. Keller-V Amsberg Gunhild, et al.
VA	Pharmacokinetics of Dasatinib for Philadelphia- Positive Acute Lymphocytic Leukemia with Acquired T315I mutation. Journal of hematology & oncology. 2012. Takahashi Naoto, et al.
	Clinical pharmacokinetics of tyrosine kinase inhibitors: focus on pyrimidines, pyridines and pyrroles. Clinical pharmacokinetics. 2011. Di Gion Paola, et al.
	Chemotherapeutic agents circumvent emergence of dasatinib-resistant BCR-ABL kinase mutations in a precise mouse model of Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood. 2011. Boulos Nidal, et al.
	Systematic review of pharmacoeconomic studies of pharmacogenomic tests. Pharmacogenomics. 2010. Beaulieu Mathieu, et al.
	Evolving novel anti-HER2 strategies. The lancet oncology. 2009. Jones Kellie L, et al.
	Overriding imatinib resistance with a novel ABL kinase inhibitor. Science (New York, N.Y.). 2004. Shah Neil P, et al.

LinkOuts

Web Resource:: Wikipedia
National Drug Code Directory:: 0003-0527-11
DrugBank:: DB01254
ChEBI:: 49375

KEGG Drug:: D03658
PubChem Compound:: 3062316
PubChem Substance:: 10061134; 46505143
BindingDB:: 13216

ChemSpider:: 2323020
Therapeutic Targets Database:: DAP000004
FDA Drug Label at DailyMed:: 4764f37b-c9e6-4ede-bcc2-8a03b7c521df

Clinical Trials

These are trials that mention dasatinib and are related to either pharmacogenetics or pharmacogenomics.

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NURSA Datasets

provided by nursa.org

No NURSA datasets available.

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Sources for PharmGKB drug information: DrugBank, PubChem.