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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
Tenifatecan (also known as SN2310 or tocopherol succinate-SN38), camptothecin, is an injectable emulsion composed of vitamin E, a succinate derivative, as well as 7-ethyl-10-hydroxycamptothecin (SN-38), the active metabolite of irinotecan. It is known that SN-38 binds to and inhibits topoisomerase I by stabilizing the cleavable complex between topoisomerase I and DNA, resulting in DNA breaks, inhibition of DNA replication, and apoptosis. Tenifatecan successfully completed phase I clinical trial in patients with advanced solid tumors. Achieve Life Sciences, the company that is developing this drug, are currently exploring options to out-license tenifatecan.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.74 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
Apoptosis induced by culturing MH134 cells in the presence of porcine skin gelatin in vitro.
2002 Aug
Irinotecan pharmacokinetics-pharmacodynamics: the clinical relevance of prolonged exposure to SN-38.
2002 Jul 15
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
Clinical pharmacokinetics of irinotecan and its metabolites in relation with diarrhea.
2002 Sep
Common human UGT1A polymorphisms and the altered metabolism of irinotecan active metabolite 7-ethyl-10-hydroxycamptothecin (SN-38).
2002 Sep
Functional characterization of human UDP-glucuronosyltransferase 1A9 variant, D256N, found in Japanese cancer patients.
2003 Aug
Phase I clinical and pharmacokinetic study of irinotecan in adults with recurrent malignant glioma.
2003 Aug 1
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
Breast cancer resistance protein (BCRP/ABCG2) induces cellular resistance to HIV-1 nucleoside reverse transcriptase inhibitors.
2003 Jan
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
Determination by liquid chromatography with fluorescence detection of total 7-ethyl-10-hydroxy-camptothecin (SN-38) in beagle dog plasma after intravenous administration of liposome-based SN-38 (LE-SN38).
2003 Jul 5
Effect of intrapatient dosage escalation of irinotecan on its pharmacokinetics in pediatric patients who have high-grade gliomas and receive enzyme-inducing anticonvulsant therapy.
2003 May 1
Activation of a camptothecin prodrug by specific carboxylesterases as predicted by quantitative structure-activity relationship and molecular docking studies.
2003 Nov
Simple non-ion-paired high-performance liquid chromatographic method for simultaneous quantitation of carboxylate and lactone forms of 14 new camptothecin derivatives.
2003 Sep 25
Phase I and pharmacokinetic study of irinotecan in combination with R115777, a farnesyl protein transferase inhibitor.
2004 Apr 19
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
Development and characterization of a novel liposome-based formulation of SN-38.
2004 Feb 11
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
Laminin-5 offsets the efficacy of gefitinib ('Iressa') in hepatocellular carcinoma cells.
2004 Nov 29
Identification of the cytosolic carboxylesterase catalyzing the 5'-deoxy-5-fluorocytidine formation from capecitabine in human liver.
2004 Oct
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
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
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
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
Effect of milk thistle (Silybum marianum) on the pharmacokinetics of irinotecan.
2005 Nov 1
Glucuronidation of trans-resveratrol by human liver and intestinal microsomes and UGT isoforms.
2006 Apr
Phase 1 and pharmacokinetic study of intravenous irinotecan in refractory solid tumor patients with hepatic dysfunction.
2006 Jun 15
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
Functional SNPs of the breast cancer resistance protein-therapeutic effects and inhibitor development.
2006 Mar 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 Vivo Use Guide
Unknown
Route of Administration: Unknown
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
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 Fri Dec 15 15:42:24 GMT 2023 , Edited by admin on Fri Dec 15 15:42:24 GMT 2023
FDA ORPHAN DRUG 513715
Created by admin on Fri Dec 15 15:42:24 GMT 2023 , Edited by admin on Fri Dec 15 15:42:24 GMT 2023
Code System Code Type Description
CAS
86639-52-3
Created by admin on Fri Dec 15 15:42:24 GMT 2023 , Edited by admin on Fri Dec 15 15:42:24 GMT 2023
PRIMARY
PUBCHEM
104842
Created by admin on Fri Dec 15 15:42:24 GMT 2023 , Edited by admin on Fri Dec 15 15:42:24 GMT 2023
PRIMARY
FDA UNII
0H43101T0J
Created by admin on Fri Dec 15 15:42:24 GMT 2023 , Edited by admin on Fri Dec 15 15:42:24 GMT 2023
PRIMARY
EVMPD
SUB188424
Created by admin on Fri Dec 15 15:42:24 GMT 2023 , Edited by admin on Fri Dec 15 15:42:24 GMT 2023
PRIMARY
NCI_THESAURUS
C61618
Created by admin on Fri Dec 15 15:42:24 GMT 2023 , Edited by admin on Fri Dec 15 15:42:24 GMT 2023
PRIMARY
RS_ITEM_NUM
1347631
Created by admin on Fri Dec 15 15:42:24 GMT 2023 , Edited by admin on Fri Dec 15 15:42:24 GMT 2023
PRIMARY
DRUG BANK
DB05482
Created by admin on Fri Dec 15 15:42:24 GMT 2023 , Edited by admin on Fri Dec 15 15:42:24 GMT 2023
PRIMARY
SMS_ID
100000174485
Created by admin on Fri Dec 15 15:42:24 GMT 2023 , Edited by admin on Fri Dec 15 15:42:24 GMT 2023
PRIMARY
CHEBI
8988
Created by admin on Fri Dec 15 15:42:24 GMT 2023 , Edited by admin on Fri Dec 15 15:42:24 GMT 2023
PRIMARY
WIKIPEDIA
SN-38
Created by admin on Fri Dec 15 15:42:24 GMT 2023 , Edited by admin on Fri Dec 15 15:42:24 GMT 2023
PRIMARY
EPA CompTox
DTXSID4040399
Created by admin on Fri Dec 15 15:42:24 GMT 2023 , Edited by admin on Fri Dec 15 15:42:24 GMT 2023
PRIMARY