Details of the Drug

General Information of Drug (ID: DM3ZL7D)

Drug Name

Edotecarin

Synonyms

ED-749; Edotecarin < Prop INN; J-107088; PF-804950; 12-(beta-D-Glucopyranosyl)-2,10-dihydroxy-6-[2-hydroxy-1-(hydroxymethyl)ethylamino]-6,7,12,13-tetrahydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7-dione

Indication

Disease Entry	ICD 11	Status	REF
Gastric adenocarcinoma	2B72	Phase 3	[1]

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 3

Molecular Weight (mw)

608.6

Topological Polar Surface Area (xlogp)

-0.7

Rotatable Bond Count (rotbonds)

6

Hydrogen Bond Donor Count (hbonddonor)

10

Hydrogen Bond Acceptor Count (hbondacc)

12

ADMET Property

Half-life: The concentration or amount of drug in body reduced by one-half in 20 - 25 hours [2]

Chemical Identifiers

Formula: C29H28N4O11
IUPAC Name: 13-(1,3-dihydroxypropan-2-ylamino)-6,20-dihydroxy-3-[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione
Canonical SMILES: C1=CC2=C(C=C1O)NC3=C4C(=C5C(=C23)C(=O)N(C5=O)NC(CO)CO)C6=C(N4[C@H]7[C@@H]([C@H]([C@@H]([C@H](O7)CO)O)O)O)C=C(C=C6)O
InChI: InChI=1S/C29H28N4O11/c34-7-10(8-35)31-33-27(42)20-18-13-3-1-11(37)5-15(13)30-22(18)23-19(21(20)28(33)43)14-4-2-12(38)6-16(14)32(23)29-26(41)25(40)24(39)17(9-36)44-29/h1-6,10,17,24-26,29-31,34-41H,7-9H2/t17-,24-,25+,26-,29-/m1/s1
InChIKey: QMVPQBFHUJZJCS-NTKFZFFISA-N

Cross-matching ID

PubChem CID: 9808998
CAS Number: 174402-32-5
DrugBank ID: DB04882
TTD ID: D0I1DW
VARIDT ID: DR01450

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
DNA topoisomerase I (TOP1)	TTGTQHC	TOP1_HUMAN	Inhibitor	[1]

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Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[3]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease

Gastric adenocarcinoma

ICD Disease Classification

2B72

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
DNA topoisomerase I (TOP1)	DTT	TOP1	6.65E-01	0.2	0.39
Breast cancer resistance protein (ABCG2)	DTP	BCRP	3.87E-47	-1.28E+00	-1.63E+00

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

References

1	Edotecarin: a novel topoisomerase I inhibitor. Clin Colorectal Cancer. 2005 May;5(1):27-36.
2	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
3	Pharmacogenomic importance of ABCG2. Pharmacogenomics. 2008 Aug;9(8):1005-9.
4	Doxorubicin transport by RALBP1 and ABCG2 in lung and breast cancer. Int J Oncol. 2007 Mar;30(3):717-25.
5	Wild-type breast cancer resistance protein (BCRP/ABCG2) is a methotrexate polyglutamate transporter. Cancer Res. 2003 Sep 1;63(17):5538-43.
6	The effect of low pH on breast cancer resistance protein (ABCG2)-mediated transport of methotrexate, 7-hydroxymethotrexate, methotrexate diglutamate, folic acid, mitoxantrone, topotecan, and resveratrol in in vitro drug transport models. Mol Pharmacol. 2007 Jan;71(1):240-9.
7	Role of BCRP as a biomarker for predicting resistance to 5-fluorouracil in breast cancer. Cancer Chemother Pharmacol. 2009 May;63(6):1103-10.
8	Inhibiting the function of ABCB1 and ABCG2 by the EGFR tyrosine kinase inhibitor AG1478. Biochem Pharmacol. 2009 Mar 1;77(5):781-93.
9	Sterol transport by the human breast cancer resistance protein (ABCG2) expressed in Lactococcus lactis. J Biol Chem. 2003 Jun 6;278(23):20645-51.
10	The phytoestrogen genistein enhances multidrug resistance in breast cancer cell lines by translational regulation of ABC transporters. Cancer Lett. 2016 Jun 28;376(1):165-72.
11	Curcumin inhibits the activity of ABCG2/BCRP1, a multidrug resistance-linked ABC drug transporter in mice. Pharm Res. 2009 Feb;26(2):480-7.
12	Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump. Blood. 2004 Nov 1;104(9):2940-2.
13	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
14	Luteolin, an emerging anti-cancer flavonoid, poisons eukaryotic DNA topoisomerase I. Biochem J. 2002 Sep 1;366(Pt 2):653-61.
15	Impact of natural products on developing new anti-cancer agents. Chem Rev. 2009 Jul;109(7):3012-43.
16	Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
17	Characterization of protein kinase chk1 essential for the cell cycle checkpoint after exposure of human head and neck carcinoma A253 cells to a novel topoisomerase I inhibitor BNP1350. Mol Pharmacol.2000 Mar;57(3):453-9.
18	Topoisomerase I inhibitors: camptothecins and beyond. Nat Rev Cancer. 2006 Oct;6(10):789-802.
19	Phase I study of topoisomerase I inhibitor exatecan mesylate (DX-8951f) given as weekly 24-hour infusions three of every four weeks. Clin Cancer Res. 2001 Dec;7(12):3963-70.
20	Rubitecan. Expert Opin Investig Drugs. 2006 Jan;15(1):71-9.
21	Nonclinical pharmacokinetics and activity of etirinotecan pegol (NKTR-102), a long-acting topoisomerase 1 inhibitor, in multiple cancer models. Cancer Chemother Pharmacol. 2014 Dec;74(6):1125-37.