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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=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 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
149124
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8504
 0.74 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Preclinical
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
Pharmacokinetics of SN2310, an injectable emulsion that incorporates a new derivative of SN-38 in patients with advanced solid tumors.
2011-10
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.
2007-09
A phase II study of biweekly dose-intensified oral capecitabine plus irinotecan (bXELIRI) for patients with advanced or metastatic gastric cancer.
2007-05-21
Copper-transporting P-type ATPase, ATP7A, confers multidrug resistance and its expression is related to resistance to SN-38 in clinical colon cancer.
2007-05-15
Crystal structure of the Geobacillus stearothermophilus carboxylesterase Est55 and its activation of prodrug CPT-11.
2007-03-16
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.
2007-02-19
Effects of green tea compounds on irinotecan metabolism.
2007-02
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.
2007-01-15
The contribution of intestinal UDP-glucuronosyltransferases in modulating 7-ethyl-10-hydroxy-camptothecin (SN-38)-induced gastrointestinal toxicity in rats.
2007-01
Three-week schedule of irinotecan plus cisplatin in patients with previously untreated extensive-stage small-cell lung cancer.
2006-12-18
The novel UGT1A9 intronic I399 polymorphism appears as a predictor of 7-ethyl-10-hydroxycamptothecin glucuronidation levels in the liver.
2006-07
Phase 1 and pharmacokinetic study of intravenous irinotecan in refractory solid tumor patients with hepatic dysfunction.
2006-06-15
Radiosensitizers in cervical cancer. Cisplatin and beyond.
2006-05-08
A phase II study of FOLFIRI-3 (double infusion of irinotecan combined with LV5FU) after FOLFOX in advanced colorectal cancer patients.
2006-05-08
HPLC method for determination of SN-38 content and SN-38 entrapment efficiency in a novel liposome-based formulation, LE-SN38.
2006-05-03
Glucuronidation of trans-resveratrol by human liver and intestinal microsomes and UGT isoforms.
2006-04
Irinotecan inactivation is modulated by epigenetic silencing of UGT1A1 in colon cancer.
2006-03-15
Functional SNPs of the breast cancer resistance protein-therapeutic effects and inhibitor development.
2006-03-08
Role of ABCG2 as a biomarker for predicting resistance to CPT-11/SN-38 in lung cancer.
2006-03
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.
2006-03
SW-620 cells treated with topoisomerase I inhibitor SN-38: gene expression profiling.
2005-12-23
Differential UGT1A1 induction by chrysin in primary human hepatocytes and HepG2 Cells.
2005-12
Effect of milk thistle (Silybum marianum) on the pharmacokinetics of irinotecan.
2005-11-01
pH-dependent association of SN-38 with lipid bilayers of a novel liposomal formulation.
2005-08-11
Breast cancer resistance protein: molecular target for anticancer drug resistance and pharmacokinetics/pharmacodynamics.
2005-08
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.
2005-07
In vitro and in vivo irinotecan-induced changes in expression profiles of cell cycle and apoptosis-associated genes in acute myeloid leukemia cells.
2005-06
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.
2005-06
Irinotecan pharmacokinetic and pharmacogenomic alterations induced by methylselenocysteine in human head and neck xenograft tumors.
2005-05
Secretory transport of irinotecan metabolite SN-38 across isolated intestinal tissue.
2005-05
Uptake of irinotecan metabolite SN-38 by the human intestinal cell line Caco-2.
2005-05
Preclinical safety, pharmacokinetics and antitumor efficacy profile of liposome-entrapped SN-38 formulation.
2005-04-09
The role of checkpoint kinase 1 in sensitivity to topoisomerase I poisons.
2005-04-08
Methylseleninic acid potentiates apoptosis induced by chemotherapeutic drugs in androgen-independent prostate cancer cells.
2005-03-15
A phase I clinical and pharmacokinetic study of capecitabine (Xeloda) and irinotecan combination therapy (XELIRI) in patients with metastatic gastrointestinal tumours.
2005-03-14
Establishment of a 7-ethyl-10-hydroxy-camptothecin-resistant small cell lung cancer cell line.
2005-03-02
Synthesis and antitumor activity of A-ring modified hexacyclic analogues of camptothecin.
2005-03
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.
2005-03
Racial variability in haplotype frequencies of UGT1A1 and glucuronidation activity of a novel single nucleotide polymorphism 686C> T (P229L) found in an African-American.
2005-03
Antitumour activity of XR5944 in vitro and in vivo in combination with 5-fluorouracil and irinotecan in colon cancer cell lines.
2005-02-28
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).
2005-02-07
Estrogen-mediated post transcriptional down-regulation of breast cancer resistance protein/ABCG2.
2005-01-15
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.
2004-12-01
Pharmacogenetics of human carboxylesterase 2, an enzyme involved in the activation of irinotecan into SN-38.
2004-12
Laminin-5 offsets the efficacy of gefitinib ('Iressa') in hepatocellular carcinoma cells.
2004-11-29
A phase I trial of pharmacologic modulation of irinotecan with cyclosporine and phenobarbital.
2004-11
Multicentre phase II study of bifractionated CPT-11 with bimonthly leucovorin and 5-fluorouracil in patients with metastatic colorectal cancer pretreated with FOLFOX.
2004-10-18
A randomised phase II multicentre trial of irinotecan (CPT-11) using four different schedules in patients with metastatic colorectal cancer.
2004-10-18
Enhanced therapeutic efficacy of a novel liposome-based formulation of SN-38 against human tumor models in SCID mice.
2004-09
MDR1, MRP1 and MRP2 genotypes and in vitro chemosensitivity in Japanese patients with colorectal adenocarcinomas.
2004
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 Mon Mar 31 18:06:11 GMT 2025
Edited
by admin
on Mon Mar 31 18:06:11 GMT 2025
Record UNII
0H43101T0J
Record Status Validated (UNII)
Record Version
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Name Type Language
SN38
WHO-DD  
Preferred Name English
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
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 Mon Mar 31 18:06:11 GMT 2025 , Edited by admin on Mon Mar 31 18:06:11 GMT 2025
FDA ORPHAN DRUG 513715
Created by admin on Mon Mar 31 18:06:11 GMT 2025 , Edited by admin on Mon Mar 31 18:06:11 GMT 2025
Code System Code Type Description
CAS
86639-52-3
Created by admin on Mon Mar 31 18:06:11 GMT 2025 , Edited by admin on Mon Mar 31 18:06:11 GMT 2025
PRIMARY
PUBCHEM
104842
Created by admin on Mon Mar 31 18:06:11 GMT 2025 , Edited by admin on Mon Mar 31 18:06:11 GMT 2025
PRIMARY
FDA UNII
0H43101T0J
Created by admin on Mon Mar 31 18:06:11 GMT 2025 , Edited by admin on Mon Mar 31 18:06:11 GMT 2025
PRIMARY
EVMPD
SUB188424
Created by admin on Mon Mar 31 18:06:11 GMT 2025 , Edited by admin on Mon Mar 31 18:06:11 GMT 2025
PRIMARY
NCI_THESAURUS
C61618
Created by admin on Mon Mar 31 18:06:11 GMT 2025 , Edited by admin on Mon Mar 31 18:06:11 GMT 2025
PRIMARY
RS_ITEM_NUM
1347631
Created by admin on Mon Mar 31 18:06:11 GMT 2025 , Edited by admin on Mon Mar 31 18:06:11 GMT 2025
PRIMARY
DRUG BANK
DB05482
Created by admin on Mon Mar 31 18:06:11 GMT 2025 , Edited by admin on Mon Mar 31 18:06:11 GMT 2025
PRIMARY
SMS_ID
100000174485
Created by admin on Mon Mar 31 18:06:11 GMT 2025 , Edited by admin on Mon Mar 31 18:06:11 GMT 2025
PRIMARY
CHEBI
8988
Created by admin on Mon Mar 31 18:06:11 GMT 2025 , Edited by admin on Mon Mar 31 18:06:11 GMT 2025
PRIMARY
WIKIPEDIA
SN-38
Created by admin on Mon Mar 31 18:06:11 GMT 2025 , Edited by admin on Mon Mar 31 18:06:11 GMT 2025
PRIMARY
EPA CompTox
DTXSID4040399
Created by admin on Mon Mar 31 18:06:11 GMT 2025 , Edited by admin on Mon Mar 31 18:06:11 GMT 2025
PRIMARY
Related Record Type Details
DNA TOPOISOMERASE 1
TARGET -> INHIBITOR
MRP-1
TRANSPORTER -> SUBSTRATE
ATP-BINDING CASSETTE SUB-FAMILY G MEMBER 2
TRANSPORTER -> INHIBITOR
PLASMA PROTEIN FRACTION (HUMAN)
BINDER->LIGAND
The plasma protein to whichSN-38 predominantly binds is albumin.
BINDING
Structure of 7-Ethyl-10-hydroxy camptothecin, (rac)-
RACEMATE -> ENANTIOMER
SACITUZUMAB GOVITECAN
CONJUGATE -> TOXIN
Related Record Type Details
Structure of NEV-801
PRODRUG -> METABOLITE ACTIVE
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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