Details of the Drug-Related molecule(s) Expression Atlas

General Information of Drug (ID: DMTI8YE)

Drug Name

Bosutinib Drug Info

Synonyms

SKI 606; SKI606; Bosutinib (USAN); PF-5208763; SKI-606; Xy]-3-quinolinecarbonitrile; 4-((2,4-dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methyl-1-piperazinyl)propoxy)-3-quinolinecarbonitrile; 4-((2,4-dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile; 4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinoline-3-carbonitrile; 4-[(2,4-Dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(4-methyl-1-piperazinyl)propo; 4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinoline-3-carbonitrile; Bosutinib (BCR-ABL inhibitor 3rd gen)

Indication

Disease Entry	ICD 11	Status	REF
Blast phase chronic myelogenous leukemia, BCR-ABL1 positive		Approved	[1]
Breast cancer	2C60-2C65	Approved	[2]

Therapeutic Class

Anticancer Agents

Cross-matching ID

PubChem CID: 5328940
ChEBI ID: CHEBI:39112
CAS Number: CAS 380843-75-4
TTD Drug ID: DMTI8YE
VARIDT Drug ID: DR00253
INTEDE Drug ID: DR0224
ACDINA Drug ID: D00075

Molecule(s) Related to This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Proto-oncogene c-Src (SRC)	TT6PKBN	SRC_HUMAN	Inhibitor	[3]
Tyrosine-protein kinase ABL1 (ABL)	TT3PJMV	ABL1_HUMAN	Inhibitor	[3]

------------------------------------------------------------------------------------

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	Highest Status	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Approved	[4]

------------------------------------------------------------------------------------

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	Highest Status	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Approved	[5]

------------------------------------------------------------------------------------

The Expression Level of Molecule(s) in Normal Tissue of Major ADME-Related Organs

Molecule	Molecule Type	Gene Name	Liver	Colon	Kidney	Small Intestine
Proto-oncogene c-Src (SRC)	DTT	SRC	2.907	3.35	3.498	4.75
P-glycoprotein 1 (ABCB1)	DTP	P-GP	7.009	6.988	7.442	8.135
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	11.692	6.58	4.984	9.089

Molecule Expression Atlas in Normal Tissue of Major ADME-related organs

The Expression Level of Molecule(s) between Disease Section and Healthy Individual Tissue

The Studied Disease

Blast phase chronic myelogenous leukemia, BCR-ABL1 positive

ICD Disease Classification

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Tyrosine-protein kinase ABL1 (ABL)	DTT	ABL1	9.65E-34	0.48	1.49
P-glycoprotein 1 (ABCB1)	DTP	P-GP	4.70E-06	-5.80E-02	-1.98E-01
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	7.29E-03	-3.47E-02	-1.80E-01

Molecular Expression Atlas between Disease Section and Healthy Individual Tissue

References

1	Bosutinib FDA Label
2	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5710).
3	A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22.
4	In vitro and in vivo identification of ABCB1 as an efflux transporter of bosutinib. J Hematol Oncol. 2015 Jul 7;8:81.
5	In vitro assessment of time-dependent inhibitory effects on CYP2C8 and CYP3A activity by fourteen protein kinase inhibitors. Drug Metab Dispos. 2014 Jul;42(7):1202-9.