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

General Information of Drug (ID: DMI6E0R)

Drug Name

Midostaurin Drug Info

Synonyms

PKC412; 120685-11-2; Cgp 41251; 4'-N-Benzoylstaurosporine; CGP-41251; Benzoylstaurosporine; PKC-412; RYDAPT; PKC 412; UNII-ID912S5VON; N-Benzoylstaurosporine; ID912S5VON; CHEMBL608533; CHEBI:63452; Cgp 41 251; N-[(5S,6R,7R,9R)-6-methoxy-5-methyl-14-oxo-6,7,8,9,15,16-hexahydro-5H,14H-5,9-epoxy-4b,9a,15-triazadibenzo[b,h]cyclonona[1,2,3,4-jkl]cyclopenta[e]-as-indacen-7-yl]-N-methylbenzamide; PKC-412(Midostaurin); Midostaurin (PKC412); Midostaurin (USAN/INN); Midostaurin [USAN:INN]; CGP 41231; Rydapt (TN); CPG 41251

Indication

Disease Entry	ICD 11	Status	REF
Acute myeloid leukaemia	2A60	Approved	[1]
Systemic mastocytosis	2A21.0	Approved	[2]
Chronic myelomonocytic leukaemia	2A40	Phase 2	[3]
Colorectal cancer	2B91.Z	Phase 1	[3]

Therapeutic Class

Anticancer Agents

Cross-matching ID

PubChem CID: 9829523
ChEBI ID: CHEBI:63452
CAS Number: CAS 120685-11-2
TTD Drug ID: DMI6E0R
VARIDT Drug ID: DR01370
INTEDE Drug ID: DR1090
ACDINA Drug ID: D00431

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	Inhibitor	[4]
Protein kinase C gamma (PRKCG)	TTRFOXJ	KPCG_HUMAN	Inhibitor	[4]

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Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	Highest Status	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Approved	[5]

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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	[6]

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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
Protein kinase C gamma (PRKCG)	DTT	PRKCG	2.104	0.848	0.678	1.848
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

Acute myeloid leukaemia

ICD Disease Classification

2A60

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
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
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	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2018
2	2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
3	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: 5702).
4	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.
5	Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
6	Midostaurin, a novel protein kinase inhibitor for the treatment of acute myelogenous leukemia: insights from human absorption, metabolism, and excretion studies of a BDDCS II drug. Drug Metab Dispos. 2017 May;45(5):540-555.