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Details

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

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

SMILES

CCC1=C2C=C(O)C=CC2=NC3=C1CN4C3=CC5=C(COC(=O)[C@]5(O)CC)C4=O

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
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

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

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.74 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
PubMed

PubMed

TitleDatePubMed
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
Pharmacogenetics of human carboxylesterase 2, an enzyme involved in the activation of irinotecan into SN-38.
2004 Dec
Enhanced 7-ethyl-10-hydroxycamptothecin (SN-38) lethality by methylselenocysteine is associated with Chk2 phosphorylation at threonine-68 and down-regulation of Cdc6 expression.
2004 Jul
Potential interactions between irinotecan and rifampin in a patient with small-cell lung cancer.
2004 Jun
A phase I trial of pharmacologic modulation of irinotecan with cyclosporine and phenobarbital.
2004 Nov
Laminin-5 offsets the efficacy of gefitinib ('Iressa') in hepatocellular carcinoma cells.
2004 Nov 29
Establishment of a 7-ethyl-10-hydroxy-camptothecin-resistant small cell lung cancer cell line.
2004 Nov-Dec
Identification of the cytosolic carboxylesterase catalyzing the 5'-deoxy-5-fluorocytidine formation from capecitabine in human liver.
2004 Oct
Multicentre phase II study of bifractionated CPT-11 with bimonthly leucovorin and 5-fluorouracil in patients with metastatic colorectal cancer pretreated with FOLFOX.
2004 Oct 18
Enhanced therapeutic efficacy of a novel liposome-based formulation of SN-38 against human tumor models in SCID mice.
2004 Sep
Gefitinib reverses breast cancer resistance protein-mediated drug resistance.
2004 Sep
ABCG2 pharmacogenetics: ethnic differences in allele frequency and assessment of influence on irinotecan disposition.
2004 Sep 1
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
A simple and sensitive LC/MS/MS assay for 7-ethyl-10-hydroxycamptothecin (SN-38) in mouse plasma and tissues: application to pharmacokinetic study of liposome entrapped SN-38 (LE-SN38).
2005 Feb 7
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
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
The crystal structure of the complex of the anticancer prodrug 7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxycamptothecin (CPT-11) with Torpedo californica acetylcholinesterase provides a molecular explanation for its cholinergic action.
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
Racial variability in haplotype frequencies of UGT1A1 and glucuronidation activity of a novel single nucleotide polymorphism 686C> T (P229L) found in an African-American.
2005 Mar
A phase I clinical and pharmacokinetic study of capecitabine (Xeloda) and irinotecan combination therapy (XELIRI) in patients with metastatic gastrointestinal tumours.
2005 Mar 14
Methylseleninic acid potentiates apoptosis induced by chemotherapeutic drugs in androgen-independent prostate cancer cells.
2005 Mar 15
Irinotecan pharmacokinetic and pharmacogenomic alterations induced by methylselenocysteine in human head and neck xenograft tumors.
2005 May
Secretory transport of irinotecan metabolite SN-38 across isolated intestinal tissue.
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
Three-week schedule of irinotecan plus cisplatin in patients with previously untreated extensive-stage small-cell lung cancer.
2006 Dec 18
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
Radiosensitizers in cervical cancer. Cisplatin and beyond.
2006 May 8
A phase II study of FOLFIRI-3 (double infusion of irinotecan combined with LV5FU) after FOLFOX in advanced colorectal cancer patients.
2006 May 8
Effects of green tea compounds on irinotecan metabolism.
2007 Feb
The thermodynamic dissociation constants of the anticancer drugs camptothecine, 7-ethyl-10-hydroxycamptothecine, 10-hydroxycamptothecine and 7-ethylcamptothecine by the least-squares nonlinear regression of multiwavelength spectrophotometric pH-titration data.
2007 Feb 19
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
A phase II study of biweekly dose-intensified oral capecitabine plus irinotecan (bXELIRI) for patients with advanced or metastatic gastric cancer.
2007 May 21
Involvement of up-regulation of hepatic breast cancer resistance protein in decreased plasma concentration of 7-ethyl-10-hydroxycamptothecin (SN-38) by coadministration of S-1 in rats.
2007 Sep
Patents

Sample Use Guides

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 Mon Oct 21 21:15:53 UTC 2019
Edited
by admin
on Mon Oct 21 21:15:53 UTC 2019
Record UNII
0H43101T0J
Record Status Validated (UNII)
Record Version
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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
IRINOTECAN RELATED COMPOUND B [USP-RS]
Common Name English
SN-38
Code English
SN 38 [WHO-DD]
Common Name English
S-(+)-7-ETHYL-10-HYDROXYCAMPOTHECIN
Common Name English
SN 38
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
NK 012
Code English
IT-141
Code English
Classification Tree Code System Code
FDA ORPHAN DRUG 513715
Created by admin on Mon Oct 21 21:15:53 UTC 2019 , Edited by admin on Mon Oct 21 21:15:53 UTC 2019
Code System Code Type Description
CAS
86639-52-3
Created by admin on Mon Oct 21 21:15:53 UTC 2019 , Edited by admin on Mon Oct 21 21:15:53 UTC 2019
PRIMARY
PUBCHEM
104842
Created by admin on Mon Oct 21 21:15:53 UTC 2019 , Edited by admin on Mon Oct 21 21:15:53 UTC 2019
PRIMARY
EVMPD
SUB188424
Created by admin on Mon Oct 21 21:15:53 UTC 2019 , Edited by admin on Mon Oct 21 21:15:53 UTC 2019
PRIMARY
NCI_THESAURUS
C61618
Created by admin on Mon Oct 21 21:15:53 UTC 2019 , Edited by admin on Mon Oct 21 21:15:53 UTC 2019
PRIMARY
WIKIPEDIA
SN-38
Created by admin on Mon Oct 21 21:15:53 UTC 2019 , Edited by admin on Mon Oct 21 21:15:53 UTC 2019
PRIMARY
EPA CompTox
86639-52-3
Created by admin on Mon Oct 21 21:15:53 UTC 2019 , Edited by admin on Mon Oct 21 21:15:53 UTC 2019
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
TRANSPORTER -> INHIBITOR
CONJUGATE -> TOXIN
Related Record Type Details
PRODRUG -> METABOLITE ACTIVE
PARENT -> METABOLITE ACTIVE
PRODRUG -> METABOLITE ACTIVE
PRODRUG -> METABOLITE ACTIVE
Related Record Type Details
ACTIVE MOIETY