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Details

Stereochemistry ABSOLUTE
Molecular Formula C22H20N2O5
Molecular Weight 392.4054
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

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

SMILES

CCc1c2cc(ccc2nc-3c1Cn4c3cc5c(COC(=O)[C@@]5(CC)O)c4=O)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 392.4054
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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.739999999999999991 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
PubMed

PubMed

TitleDatePubMed
Characterization of a novel mechanism accounting for the adverse cholinergic effects of the anticancer drug irinotecan.
2001 Jan
A new metabolite of irinotecan in which formation is mediated by human hepatic cytochrome P-450 3A4.
2001 Nov
The role of topoisomerase I inhibitor in cisplatin-resistant ovarian cancer.
2001 Sep
Induction of biphasic DNA double strand breaks and activation of multiple repair protein complexes by DNA topoisomerase I drug 7-ethyl-10-hydroxy-camptothecin.
2002 Apr
Apoptosis induced by culturing MH134 cells in the presence of porcine skin gelatin in vitro.
2002 Aug
Synergistic effects of topoisomerase I inhibitor, 7-ethyl-10-hydroxycamptothecin, and irradiation in a cisplatin-resistant human small cell lung cancer cell line.
2002 Jan
Intestinal alkalization as a possible preventive mechanism in irinotecan (CPT-11)-induced diarrhea.
2002 Jan 1
Current perspectives on the clinical experience, pharmacology, and continued development of the camptothecins.
2002 Mar
An analytical method for irinotecan (CPT-11) and its metabolites using a high-performance liquid chromatography: parallel detection with fluorescence and mass spectrometry.
2002 May
Schedule-selective biochemical modulation of 5-fluorouracil in advanced colorectal cancer--a phase II study.
2002 May 2
Combination of 5-fluorouracil and irinotecan on modulation of thymidylate synthase and topoisomerase I expression and cell cycle regulation in human colon cancer LoVo cells: clinical relevance.
2002 Nov
Functional characterization of human UDP-glucuronosyltransferase 1A9 variant, D256N, found in Japanese cancer patients.
2003 Aug
A sensitive and rapid liquid chromatography tandem mass spectrometry method for quantitative determination of 7-ethyl-10-hydroxycamptothecin (SN-38) in human plasma containing liposome-based SN-38 (LE-SN38).
2003 Dec
Glucuronidation of 7-ethyl-10-hydroxycamptothecin (SN-38), an active metabolite of irinotecan (CPT-11), by human UGT1A1 variants, G71R, P229Q, and Y486D.
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
Alleviation of side effects induced by irinotecan hydrochloride (CPT-11) in rats by intravenous infusion.
2003 Nov
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
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
Hydrolysis of irinotecan and its oxidative metabolites, 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino] carbonyloxycamptothecin and 7-ethyl-10-[4-(1-piperidino)-1-amino]-carbonyloxycamptothecin, by human carboxylesterases CES1A1, CES2, and a newly expressed carboxylesterase isoenzyme, CES3.
2004 May
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
A randomised phase II multicentre trial of irinotecan (CPT-11) using four different schedules in patients with metastatic colorectal cancer.
2004 Oct 18
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
SW-620 cells treated with topoisomerase I inhibitor SN-38: gene expression profiling.
2005 Dec 23
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
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
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
Glucuronidation of trans-resveratrol by human liver and intestinal microsomes and UGT isoforms.
2006 Apr
Three-week schedule of irinotecan plus cisplatin in patients with previously untreated extensive-stage small-cell lung cancer.
2006 Dec 18
A phase II study of FOLFIRI-3 (double infusion of irinotecan combined with LV5FU) after FOLFOX in advanced colorectal cancer patients.
2006 May 8
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 Fri Jun 25 21:42:14 UTC 2021
Edited
by admin
on Fri Jun 25 21:42:14 UTC 2021
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
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 Fri Jun 25 21:42:14 UTC 2021 , Edited by admin on Fri Jun 25 21:42:14 UTC 2021
Code System Code Type Description
CAS
86639-52-3
Created by admin on Fri Jun 25 21:42:14 UTC 2021 , Edited by admin on Fri Jun 25 21:42:14 UTC 2021
PRIMARY
PUBCHEM
104842
Created by admin on Fri Jun 25 21:42:14 UTC 2021 , Edited by admin on Fri Jun 25 21:42:14 UTC 2021
PRIMARY
FDA UNII
0H43101T0J
Created by admin on Fri Jun 25 21:42:14 UTC 2021 , Edited by admin on Fri Jun 25 21:42:14 UTC 2021
PRIMARY
EVMPD
SUB188424
Created by admin on Fri Jun 25 21:42:14 UTC 2021 , Edited by admin on Fri Jun 25 21:42:14 UTC 2021
PRIMARY
NCI_THESAURUS
C61618
Created by admin on Fri Jun 25 21:42:14 UTC 2021 , Edited by admin on Fri Jun 25 21:42:14 UTC 2021
PRIMARY
USP_CATALOG
1347631
Created by admin on Fri Jun 25 21:42:14 UTC 2021 , Edited by admin on Fri Jun 25 21:42:14 UTC 2021
PRIMARY USP-RS
DRUG BANK
DB05482
Created by admin on Fri Jun 25 21:42:14 UTC 2021 , Edited by admin on Fri Jun 25 21:42:14 UTC 2021
PRIMARY
WIKIPEDIA
SN-38
Created by admin on Fri Jun 25 21:42:14 UTC 2021 , Edited by admin on Fri Jun 25 21:42:14 UTC 2021
PRIMARY
EPA CompTox
86639-52-3
Created by admin on Fri Jun 25 21:42:14 UTC 2021 , Edited by admin on Fri Jun 25 21:42:14 UTC 2021
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
TRANSPORTER -> INHIBITOR
BINDER->LIGAND
The plasma protein to whichSN-38 predominantly binds is albumin.
BINDING
CONJUGATE -> TOXIN
Related Record Type Details
PRODRUG -> METABOLITE ACTIVE
PARENT -> METABOLITE ACTIVE
PRODRUG -> METABOLITE ACTIVE
PRODRUG -> METABOLITE ACTIVE
Related Record Type Details
PARENT -> IMPURITY
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC INTRAVENOUS ADMINISTRATION