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Details

Stereochemistry ABSOLUTE
Molecular Formula C22H20N2O5
Molecular Weight 392.4046
Optical Activity ( + )
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of 7-ETHYL-10-HYDROXYCAMPTOTHECIN

SMILES

CCC1=C2CN3C(=CC4=C(COC(=O)[C@]4(O)CC)C3=O)C2=NC5=CC=C(O)C=C15

InChI

InChIKey=FJHBVJOVLFPMQE-QFIPXVFZSA-N
InChI=1S/C22H20N2O5/c1-3-12-13-7-11(25)5-6-17(13)23-19-14(12)9-24-18(19)8-16-15(20(24)26)10-29-21(27)22(16,28)4-2/h5-8,25,28H,3-4,9-10H2,1-2H3/t22-/m0/s1

HIDE SMILES / InChI
Molecular Formula C22H20N2O5
Molecular Weight 392.4046
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/1651156

SN38 (7-ethyl-10-hydroxy camptothecin) is a prominent and efficacious anticancer agent. It is poorly soluble in both water and pharmaceutically approved solvents; therefore, the direct formulation of SN38 in solution form is limited. SN38 is formed via hydrolysis of irinotecan by carboxylesterases and metabolized via glucuronidation by UGT1A1. Currently, the water soluble prodrug of SN38, irinotecan (CPT-11), is formulated as a low pH solution and is approved for chemotherapy. SN38 causes the strongest inhibition of DNA topoisomerase I, followed by CPT and then CPT-11. CPT-11 dose dependently shifts the position of relaxed DNA in the direction of nicked DNA, but SN38 and CPT shows no effect on the position of relaxed DNA. SN38 dose-dependently and time-dependently inhibit DNA synthesis. Respective IC50 values of SN38, in DNA synthesis is 0.077 uM.

Originator

Approval Year

Unknown
134361
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8228
 0.74 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Preclinical
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
Prevention of irinotecan (CPT-11)-induced diarrhea by oral alkalization combined with control of defecation in cancer patients.
2001 Apr 15
Characterization of a novel mechanism accounting for the adverse cholinergic effects of the anticancer drug irinotecan.
2001 Jan
Interaction of irinotecan (CPT-11) and its active metabolite 7-ethyl-10-hydroxycamptothecin (SN-38) with human cytochrome P450 enzymes.
2002 Apr
Enhanced clearance of topoisomerase I inhibitors from human colon cancer cells by glucuronidation.
2002 Feb 15
Intestinal alkalization as a possible preventive mechanism in irinotecan (CPT-11)-induced diarrhea.
2002 Jan 1
Irinotecan pharmacokinetics-pharmacodynamics: the clinical relevance of prolonged exposure to SN-38.
2002 Jul 15
Schedule-selective biochemical modulation of 5-fluorouracil in advanced colorectal cancer--a phase II study.
2002 May 2
Breast cancer resistance protein (BCRP/ABCG2) induces cellular resistance to HIV-1 nucleoside reverse transcriptase inhibitors.
2003 Jan
Mouse liver and kidney carboxylesterase (M-LK) rapidly hydrolyzes antitumor prodrug irinotecan and the N-terminal three quarter sequence determines substrate selectivity.
2003 Jan
Activation of a camptothecin prodrug by specific carboxylesterases as predicted by quantitative structure-activity relationship and molecular docking studies.
2003 Nov
MDR1, MRP1 and MRP2 genotypes and in vitro chemosensitivity in Japanese patients with colorectal adenocarcinomas.
2004
Characterization of inhibitors of specific carboxylesterases: development of carboxylesterase inhibitors for translational application.
2004 Aug
Lack of microvessels in well-differentiated regions of human head and neck squamous cell carcinoma A253 associated with functional magnetic resonance imaging detectable hypoxia, limited drug delivery, and resistance to irinotecan therapy.
2004 Dec 1
Development and characterization of a novel liposome-based formulation of SN-38.
2004 Feb 11
Glucuronidation as a mechanism of intrinsic drug resistance in colon cancer cells: contribution of drug transport proteins.
2004 Jan 1
The schedule-dependent enhanced cytotoxic activity of 7-ethyl-10-hydroxy-camptothecin (SN-38) in combination with Gefitinib (Iressa, ZD1839).
2004 Jul 1
Discovery of novel selective inhibitors of human intestinal carboxylesterase for the amelioration of irinotecan-induced diarrhea: synthesis, quantitative structure-activity relationship analysis, and biological activity.
2004 Jun
A phase I trial of pharmacologic modulation of irinotecan with cyclosporine and phenobarbital.
2004 Nov
Gefitinib reverses breast cancer resistance protein-mediated drug resistance.
2004 Sep
The role of checkpoint kinase 1 in sensitivity to topoisomerase I poisons.
2005 Apr 8
Breast cancer resistance protein: molecular target for anticancer drug resistance and pharmacokinetics/pharmacodynamics.
2005 Aug
pH-dependent association of SN-38 with lipid bilayers of a novel liposomal formulation.
2005 Aug 11
Differential UGT1A1 induction by chrysin in primary human hepatocytes and HepG2 Cells.
2005 Dec
SW-620 cells treated with topoisomerase I inhibitor SN-38: gene expression profiling.
2005 Dec 23
Antitumour activity of XR5944 in vitro and in vivo in combination with 5-fluorouracil and irinotecan in colon cancer cell lines.
2005 Feb 28
Estrogen-mediated post transcriptional down-regulation of breast cancer resistance protein/ABCG2.
2005 Jan 15
Preclinical safety, pharmacokinetics and antitumor efficacy profile of liposome-entrapped SN-38 formulation.
2005 Jan-Feb
Differential rates of glucuronidation for 7-ethyl-10-hydroxy-camptothecin (SN-38) lactone and carboxylate in human and rat microsomes and recombinant UDP-glucuronosyltransferase isoforms.
2005 Jul
In vitro and in vivo irinotecan-induced changes in expression profiles of cell cycle and apoptosis-associated genes in acute myeloid leukemia cells.
2005 Jun
Synthesis and antitumor activity of A-ring modified hexacyclic analogues of camptothecin.
2005 Mar
Role of organic anion transporter OATP1B1 (OATP-C) in hepatic uptake of irinotecan and its active metabolite, 7-ethyl-10-hydroxycamptothecin: in vitro evidence and effect of single nucleotide polymorphisms.
2005 Mar
Irinotecan pharmacokinetic and pharmacogenomic alterations induced by methylselenocysteine in human head and neck xenograft tumors.
2005 May
Uptake of irinotecan metabolite SN-38 by the human intestinal cell line Caco-2.
2005 May
Effect of milk thistle (Silybum marianum) on the pharmacokinetics of irinotecan.
2005 Nov 1
The novel UGT1A9 intronic I399 polymorphism appears as a predictor of 7-ethyl-10-hydroxycamptothecin glucuronidation levels in the liver.
2006 Jul
Phase 1 and pharmacokinetic study of intravenous irinotecan in refractory solid tumor patients with hepatic dysfunction.
2006 Jun 15
Role of ABCG2 as a biomarker for predicting resistance to CPT-11/SN-38 in lung cancer.
2006 Mar
Re: Yin MB, Li Z-R, Cao S, Durrani FA, Azrak RG, Frank C, and Rustum YM (2004) Enhanced 7-ethyl-10-hydroxycamptothecin (SN-38) lethality by methylselenocysteine is associated with Chk2 phosphorylation at threonin-68 and down-regulation of Cdc6 expression. Mol Pharmacol 66:153-160.
2006 Mar
Irinotecan inactivation is modulated by epigenetic silencing of UGT1A1 in colon cancer.
2006 Mar 15
Functional SNPs of the breast cancer resistance protein-therapeutic effects and inhibitor development.
2006 Mar 8
HPLC method for determination of SN-38 content and SN-38 entrapment efficiency in a novel liposome-based formulation, LE-SN38.
2006 May 3
Effects of green tea compounds on irinotecan metabolism.
2007 Feb
The contribution of intestinal UDP-glucuronosyltransferases in modulating 7-ethyl-10-hydroxy-camptothecin (SN-38)-induced gastrointestinal toxicity in rats.
2007 Jan
Schedule-dependent activity of 5-fluorouracil and irinotecan combination in the treatment of human colorectal cancer: in vitro evidence and a phase I dose-escalating clinical trial.
2007 Jan 15
Crystal structure of the Geobacillus stearothermophilus carboxylesterase Est55 and its activation of prodrug CPT-11.
2007 Mar 16
Copper-transporting P-type ATPase, ATP7A, confers multidrug resistance and its expression is related to resistance to SN-38 in clinical colon cancer.
2007 May 15
Pharmacokinetics of SN2310, an injectable emulsion that incorporates a new derivative of SN-38 in patients with advanced solid tumors.
2011 Oct
Patents

Patents

20010038851
4
JPH04139187A
2

Sample Use Guides

In Vivo Use Guide
Single intravenous doses of 15, 20, 25, and 30 mg/m(2) of SN2310 (TENIFATECAN) emulsion were administered in a total of 26 patients with advanced solid malignancies
Route of Administration: Intravenous
In Vitro Use Guide
Relaxation of SV40 DNA plasmids by type I DNA topoisomerase prepared from P388 murine leukemia cells was inhibited by 50% by SN-38 at approximately 1 uM of 7-ethyl-10-hydroxy camptothecin
Substance Class Chemical
Created
by admin
on Wed Jul 05 23:11:18 UTC 2023
Edited
by admin
on Wed Jul 05 23:11:18 UTC 2023
Record UNII
0H43101T0J
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
7-ETHYL-10-HYDROXYCAMPTOTHECIN
Common Name English
1H-PYRANO(3',4':6,7)INDOLIZINO(1,2-B)QUINOLINE-3,14(4H,12H)-DIONE, 4,11-DIETHYL-4,9-DIHYDROXY-, (4S)-
Systematic Name English
SN 38 [WHO-DD]
Common Name English
IRINOTECAN RELATED COMPOUND B [USP-RS]
Common Name English
SN-38
Code English
S-(+)-7-ETHYL-10-HYDROXYCAMPOTHECIN
Common Name English
SN38
WHO-DD  
Code English
NK012
Code English
NK-012
Code English
CAMPTOTHECIN, 7-ETHYL-10-HYDROXY-
Common Name English
IRINOTECAN RELATED COMPOUND B
USP-RS  
Common Name English
IT-141
Code English
Classification Tree Code System Code
FDA ORPHAN DRUG 840021
Created by admin on Wed Jul 05 23:11:19 UTC 2023 , Edited by admin on Wed Jul 05 23:11:19 UTC 2023
FDA ORPHAN DRUG 513715
Created by admin on Wed Jul 05 23:11:19 UTC 2023 , Edited by admin on Wed Jul 05 23:11:19 UTC 2023
Code System Code Type Description
CAS
86639-52-3
Created by admin on Wed Jul 05 23:11:19 UTC 2023 , Edited by admin on Wed Jul 05 23:11:19 UTC 2023
PRIMARY
PUBCHEM
104842
Created by admin on Wed Jul 05 23:11:19 UTC 2023 , Edited by admin on Wed Jul 05 23:11:19 UTC 2023
PRIMARY
FDA UNII
0H43101T0J
Created by admin on Wed Jul 05 23:11:19 UTC 2023 , Edited by admin on Wed Jul 05 23:11:19 UTC 2023
PRIMARY
EVMPD
SUB188424
Created by admin on Wed Jul 05 23:11:19 UTC 2023 , Edited by admin on Wed Jul 05 23:11:19 UTC 2023
PRIMARY
NCI_THESAURUS
C61618
Created by admin on Wed Jul 05 23:11:19 UTC 2023 , Edited by admin on Wed Jul 05 23:11:19 UTC 2023
PRIMARY
RS_ITEM_NUM
1347631
Created by admin on Wed Jul 05 23:11:19 UTC 2023 , Edited by admin on Wed Jul 05 23:11:19 UTC 2023
PRIMARY
DRUG BANK
DB05482
Created by admin on Wed Jul 05 23:11:19 UTC 2023 , Edited by admin on Wed Jul 05 23:11:19 UTC 2023
PRIMARY
SMS_ID
100000174485
Created by admin on Wed Jul 05 23:11:19 UTC 2023 , Edited by admin on Wed Jul 05 23:11:19 UTC 2023
PRIMARY
CHEBI
8988
Created by admin on Wed Jul 05 23:11:19 UTC 2023 , Edited by admin on Wed Jul 05 23:11:19 UTC 2023
PRIMARY
WIKIPEDIA
SN-38
Created by admin on Wed Jul 05 23:11:19 UTC 2023 , Edited by admin on Wed Jul 05 23:11:19 UTC 2023
PRIMARY
EPA CompTox
DTXSID4040399
Created by admin on Wed Jul 05 23:11:19 UTC 2023 , Edited by admin on Wed Jul 05 23:11:19 UTC 2023
PRIMARY
Related Record Type Details
DNA TOPOISOMERASE 1
TARGET -> INHIBITOR
MRP-1
TRANSPORTER -> SUBSTRATE
PLASMA PROTEIN FRACTION (HUMAN)
BINDER->LIGAND
The plasma protein to whichSN-38 predominantly binds is albumin.
BINDING
ATP-BINDING CASSETTE SUB-FAMILY G MEMBER 2
TRANSPORTER -> INHIBITOR
SACITUZUMAB GOVITECAN
CONJUGATE -> TOXIN
Related Record Type Details
Structure of GOVITECAN CYSTEINYL CONJUGATE
PRODRUG -> METABOLITE ACTIVE
SACITUZUMAB GOVITECAN
PARENT -> METABOLITE ACTIVE
FIRTECAN PEGOL
PRODRUG -> METABOLITE ACTIVE
Structure of IRINOTECAN
PRODRUG -> METABOLITE ACTIVE
Structure of LOCNARTECAN
PRODRUG -> METABOLITE ACTIVE
Related Record Type Details
Structure of IRINOTECAN HYDROCHLORIDE
PARENT -> IMPURITY
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
Related Record Type Details
Structure of 7-ETHYL-10-HYDROXYCAMPTOTHECIN
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC INTRAVENOUS ADMINISTRATION

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