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

General Information of Drug (ID: DMP6G8T)

Drug Name

Topotecan Drug Info

Synonyms

Hycamptamine; Hycamptin; Hycamtamine; Topotecane; Topotecanum; Topotecan lactone; SKF 104864; SKF-S 104864; TOPOTECAN, HYCAMTIN; Topotecan (BAN); Topotecan [INN:BAN]; Topotecane [INN-French]; Topotecanum [INN-Latin]; Topotecan Monohydrochloride, (S)-Isomer; (4S)-10-[(dimethylamino)methyl]-4-ethyl-4,9-dihydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione; (S)-10-((Dimethylamino)methyl)-4-ethyl-4,9-dihydroxy-1H-pyrano(3',4':6,7)indolizino(1,2-b)quinoline-3,14(4H,12H)-dione; (S)-10-[(DIMETHYLAMINO)METHYL]-4-ETHYL-4,9-DIHYDROXY-1H-PYRANO[3',4':6,7]INOLIZINO[1,2-B]-QUINOLINE-3,14(4H,12H)-DIONE; (S)-10-[(Dimethylamino)methyl]-4-ethyl-4,9-dihydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]-quinoline-3,14(4H,12H)-dione; (S)-10-[(Dimethylamino)methyl]-4-ethyl-4,9-dihydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione; 9-Dimethylaminomethyl-10-hydroxycamptothecin

Indication

Disease Entry	ICD 11	Status	REF
Central nervous system neoplasm		Approved	[1]
Cervical cancer	2C77.0	Approved	[1]
Epithelial ovarian cancer	2B5D	Approved	[1]
Lung cancer	2C25.0	Approved	[1]
Ovarian cancer	2C73	Approved	[2]
Solid tumour/cancer	2A00-2F9Z	Approved	[3]
Small-cell lung cancer	2C25.Y	Phase 1	[4]
Neuroblastoma	2D11.2	Investigative	[1]

Therapeutic Class

Anticancer Agents

Cross-matching ID

PubChem CID: 60700
ChEBI ID: CHEBI:63632
CAS Number: CAS 123948-87-8
TTD Drug ID: DMP6G8T
VARIDT Drug ID: DR00044
ACDINA Drug ID: D00690

Molecule(s) Related to This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
DNA topoisomerase I (TOP1)	TTGTQHC	TOP1_HUMAN	Modulator	[5]

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Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	Highest Status	REF
Multidrug resistance-associated protein 4 (ABCC4)	DTCSGPB	MRP4_HUMAN	Approved	[6]
Multidrug resistance-associated protein 1 (ABCC1)	DTSYQGK	MRP1_HUMAN	Approved	[7]
Multidrug and toxin extrusion protein 2 (SLC47A2)	DT3TX4H	S47A2_HUMAN	Approved	[8]
Multidrug and toxin extrusion protein 1 (SLC47A1)	DTZGT0P	S47A1_HUMAN	Approved	[8]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Approved	[9]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Approved	[10]

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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
Multidrug and toxin extrusion protein 1 (SLC47A1)	DTP	MATE1	8.272	1.766	7.501	1.202
P-glycoprotein 1 (ABCB1)	DTP	P-GP	7.009	6.988	7.442	8.135
Multidrug resistance-associated protein 1 (ABCC1)	DTP	MRP1	4.838	6.296	5.935	6.146
Breast cancer resistance protein (ABCG2)	DTP	BCRP	6.732	7.513	6.326	9.277
Multidrug resistance-associated protein 4 (ABCC4)	DTP	MRP4	4.797	7.054	6.875	5.42

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

Central nervous system neoplasm

ICD Disease Classification

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
DNA topoisomerase I (TOP1)	DTT	TOP1	1.05E-01	0.17	0.27
Multidrug and toxin extrusion protein 1 (SLC47A1)	DTP	MATE1	4.58E-22	-5.44E-01	-9.06E-01
P-glycoprotein 1 (ABCB1)	DTP	P-GP	3.61E-73	-1.15E+00	-1.66E+00
Multidrug resistance-associated protein 1 (ABCC1)	DTP	MRP1	1.33E-51	5.67E-01	1.25E+00
Breast cancer resistance protein (ABCG2)	DTP	BCRP	1.46E-65	-1.41E+00	-1.41E+00
Multidrug resistance-associated protein 4 (ABCC4)	DTP	MRP4	6.84E-05	8.79E-02	1.77E-01
Multidrug and toxin extrusion protein 2 (SLC47A2)	DTP	MATE2	6.25E-01	-5.97E-03	-1.97E-02

Molecular Expression Atlas between Disease Section and Healthy Individual Tissue

References

1	Topotecan 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: 7101).
3	Plant-derived compounds in clinical trials. Drug Discov Today. 2008 Feb;13(3-4):161-71.
4	ClinicalTrials.gov (NCT00765973) Topotecan Liposomes Injection for Small Cell Lung Cancer (SCLC), Ovarian Cancer and Other Advanced Solid Tumors. U.S. National Institutes of Health.
5	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
6	Topotecan is a substrate for multidrug resistance associated protein 4. Curr Drug Metab. 2006 Jan;7(1):105-18.
7	Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
8	Substrate specificity of MATE1 and MATE2-K, human multidrug and toxin extrusions/H(+)-organic cation antiporters. Biochem Pharmacol. 2007 Jul 15;74(2):359-71.
9	Differential inhibition of murine Bcrp1/Abcg2 and human BCRP/ABCG2 by the mycotoxin fumitremorgin C. Eur J Pharmacol. 2010 Oct 10;644(1-3):41-8.
10	Involvement of P-glycoprotein, multidrug resistance protein 2 and breast cancer resistance protein in the transport of belotecan and topotecan in Caco-2 and MDCKII cells. Pharm Res. 2008 Nov;25(11):2601-12.