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

General Information of Drug (ID: DMYGJQO)

Drug Name

Ponatinib Drug Info

Synonyms

Iclusig (TN)

Indication

Disease Entry	ICD 11	Status	REF
Acute lymphoblastic leukaemia	2A85	Approved	[1]
Chronic myelogenous leukaemia	2A20.0	Approved	[2]
Thyroid tumor		Approved	[2]

Cross-matching ID

Molecule(s) Related to This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Fms-like tyrosine kinase 3 (FLT-3)	TTGJCWZ	FLT3_HUMAN	Modulator	[3]
Proto-oncogene c-Ret (RET)	TT4DXQT	RET_HUMAN	Modulator	[3]
Tyrosine-protein kinase ABL1 (ABL)	TT3PJMV	ABL1_HUMAN	Modulator	[3]
Tyrosine-protein kinase Kit (KIT)	TTX41N9	KIT_HUMAN	Modulator	[3]

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Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	Highest Status	REF
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Approved	[4]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Approved	[4]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	Highest Status	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Approved	[5]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Approved	[6]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Approved	[7]

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

Molecule	Molecule Type	Gene Name	Liver	Colon	Kidney	Small Intestine
Tyrosine-protein kinase Kit (KIT)	DTT	KIT	3.766	7.517	7.379	6.916
Proto-oncogene c-Ret (RET)	DTT	RET	5.459	5.43	4.256	4.322
P-glycoprotein 1 (ABCB1)	DTP	P-GP	7.009	6.988	7.442	8.135
Breast cancer resistance protein (ABCG2)	DTP	BCRP	6.732	7.513	6.326	9.277
Cytochrome P450 3A5 (CYP3A5)	DME	CYP3A5	10.08	7.207	5.403	9.211
Cytochrome P450 2D6 (CYP2D6)	DME	CYP2D6	3.307	5.005	3.921	5.327
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

Acute lymphoblastic leukaemia

ICD Disease Classification

2A85

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Tyrosine-protein kinase Kit (KIT)	DTT	KIT	2.06E-01	-0.1	-0.14
Fms-like tyrosine kinase 3 (FLT-3)	DTT	FLT3	2.11E-01	-0.05	-0.16
P-glycoprotein 1 (ABCB1)	DTP	P-GP	9.39E-02	1.07E-01	2.80E-01
Breast cancer resistance protein (ABCG2)	DTP	BCRP	9.45E-01	-5.34E-02	-9.01E-02
Cytochrome P450 3A5 (CYP3A5)	DME	CYP3A5	9.96E-01	-3.17E-03	-1.84E-02
Cytochrome P450 2D6 (CYP2D6)	DME	CYP2D6	7.30E-01	-1.91E-02	-1.41E-01
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	1.04E-02	6.29E-02	3.54E-01

Molecular Expression Atlas between Disease Section and Healthy Individual Tissue

References

1	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: 5890).
2	Ponatinib FDA Label
3	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
4	DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. (ID: DB08901)
5	Evaluation of the effect of multiple doses of rifampin on the pharmacokinetics and safety of ponatinib in healthy subjects. Clin Pharmacol Drug Dev. 2015 Sep;4(5):354-60.
6	Novel pathways of ponatinib disposition catalyzed by CYP1A1 involving generation of potentially toxic metabolites. J Pharmacol Exp Ther. 2017 Oct;363(1):12-19.
7	Potential of ponatinib to treat chronic myeloid leukemia and acute lymphoblastic leukemia. Onco Targets Ther. 2013 Aug 20;6:1111-8.