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
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
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 |
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/21630281 | https://clinicaltrials.gov/ct2/show/NCT00385177 | http://getfilings.com/sec-filings/100308/ONCOGENEX-PHARMACEUTICALS-INC_10-K/https://www.ncbi.nlm.nih.gov/pubmed/23928356 | https://www.ncbi.nlm.nih.gov/pubmed/27108266Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/1651156
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21630281 | https://clinicaltrials.gov/ct2/show/NCT00385177 | http://getfilings.com/sec-filings/100308/ONCOGENEX-PHARMACEUTICALS-INC_10-K/https://www.ncbi.nlm.nih.gov/pubmed/23928356 | https://www.ncbi.nlm.nih.gov/pubmed/27108266
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
Targets
Primary Target | Pharmacology | Condition | Potency |
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Target ID: CHEMBL1781 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1651156 |
0.74 µM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | Unknown Approved UseUnknown |
PubMed
Title | Date | PubMed |
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Prevention of irinotecan (CPT-11)-induced diarrhea by oral alkalization combined with control of defecation in cancer patients. | 2001 Apr 15 |
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Characterization of a novel mechanism accounting for the adverse cholinergic effects of the anticancer drug irinotecan. | 2001 Jan |
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Interaction of irinotecan (CPT-11) and its active metabolite 7-ethyl-10-hydroxycamptothecin (SN-38) with human cytochrome P450 enzymes. | 2002 Apr |
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Enhanced clearance of topoisomerase I inhibitors from human colon cancer cells by glucuronidation. | 2002 Feb 15 |
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Intestinal alkalization as a possible preventive mechanism in irinotecan (CPT-11)-induced diarrhea. | 2002 Jan 1 |
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Irinotecan pharmacokinetics-pharmacodynamics: the clinical relevance of prolonged exposure to SN-38. | 2002 Jul 15 |
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Schedule-selective biochemical modulation of 5-fluorouracil in advanced colorectal cancer--a phase II study. | 2002 May 2 |
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Breast cancer resistance protein (BCRP/ABCG2) induces cellular resistance to HIV-1 nucleoside reverse transcriptase inhibitors. | 2003 Jan |
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Mouse liver and kidney carboxylesterase (M-LK) rapidly hydrolyzes antitumor prodrug irinotecan and the N-terminal three quarter sequence determines substrate selectivity. | 2003 Jan |
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Activation of a camptothecin prodrug by specific carboxylesterases as predicted by quantitative structure-activity relationship and molecular docking studies. | 2003 Nov |
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MDR1, MRP1 and MRP2 genotypes and in vitro chemosensitivity in Japanese patients with colorectal adenocarcinomas. | 2004 |
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Characterization of inhibitors of specific carboxylesterases: development of carboxylesterase inhibitors for translational application. | 2004 Aug |
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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 |
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Development and characterization of a novel liposome-based formulation of SN-38. | 2004 Feb 11 |
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Glucuronidation as a mechanism of intrinsic drug resistance in colon cancer cells: contribution of drug transport proteins. | 2004 Jan 1 |
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The schedule-dependent enhanced cytotoxic activity of 7-ethyl-10-hydroxy-camptothecin (SN-38) in combination with Gefitinib (Iressa, ZD1839). | 2004 Jul 1 |
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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 |
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A phase I trial of pharmacologic modulation of irinotecan with cyclosporine and phenobarbital. | 2004 Nov |
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Gefitinib reverses breast cancer resistance protein-mediated drug resistance. | 2004 Sep |
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The role of checkpoint kinase 1 in sensitivity to topoisomerase I poisons. | 2005 Apr 8 |
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Breast cancer resistance protein: molecular target for anticancer drug resistance and pharmacokinetics/pharmacodynamics. | 2005 Aug |
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pH-dependent association of SN-38 with lipid bilayers of a novel liposomal formulation. | 2005 Aug 11 |
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Differential UGT1A1 induction by chrysin in primary human hepatocytes and HepG2 Cells. | 2005 Dec |
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SW-620 cells treated with topoisomerase I inhibitor SN-38: gene expression profiling. | 2005 Dec 23 |
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Antitumour activity of XR5944 in vitro and in vivo in combination with 5-fluorouracil and irinotecan in colon cancer cell lines. | 2005 Feb 28 |
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Estrogen-mediated post transcriptional down-regulation of breast cancer resistance protein/ABCG2. | 2005 Jan 15 |
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Preclinical safety, pharmacokinetics and antitumor efficacy profile of liposome-entrapped SN-38 formulation. | 2005 Jan-Feb |
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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 |
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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 |
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Synthesis and antitumor activity of A-ring modified hexacyclic analogues of camptothecin. | 2005 Mar |
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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 |
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Irinotecan pharmacokinetic and pharmacogenomic alterations induced by methylselenocysteine in human head and neck xenograft tumors. | 2005 May |
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Uptake of irinotecan metabolite SN-38 by the human intestinal cell line Caco-2. | 2005 May |
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Effect of milk thistle (Silybum marianum) on the pharmacokinetics of irinotecan. | 2005 Nov 1 |
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The novel UGT1A9 intronic I399 polymorphism appears as a predictor of 7-ethyl-10-hydroxycamptothecin glucuronidation levels in the liver. | 2006 Jul |
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Phase 1 and pharmacokinetic study of intravenous irinotecan in refractory solid tumor patients with hepatic dysfunction. | 2006 Jun 15 |
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Role of ABCG2 as a biomarker for predicting resistance to CPT-11/SN-38 in lung cancer. | 2006 Mar |
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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 |
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Irinotecan inactivation is modulated by epigenetic silencing of UGT1A1 in colon cancer. | 2006 Mar 15 |
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Functional SNPs of the breast cancer resistance protein-therapeutic effects and inhibitor development. | 2006 Mar 8 |
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HPLC method for determination of SN-38 content and SN-38 entrapment efficiency in a novel liposome-based formulation, LE-SN38. | 2006 May 3 |
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Effects of green tea compounds on irinotecan metabolism. | 2007 Feb |
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The contribution of intestinal UDP-glucuronosyltransferases in modulating 7-ethyl-10-hydroxy-camptothecin (SN-38)-induced gastrointestinal toxicity in rats. | 2007 Jan |
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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 |
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Crystal structure of the Geobacillus stearothermophilus carboxylesterase Est55 and its activation of prodrug CPT-11. | 2007 Mar 16 |
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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 |
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Pharmacokinetics of SN2310, an injectable emulsion that incorporates a new derivative of SN-38 in patients with advanced solid tumors. | 2011 Oct |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21630281
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/1651156
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
Edited
Wed Jul 05 23:11:18 UTC 2023
by
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on
Wed Jul 05 23:11:18 UTC 2023
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Record UNII |
0H43101T0J
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Record Status |
Validated (UNII)
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840021
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FDA ORPHAN DRUG |
513715
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SN-38
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DTXSID4040399
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Related Record | Type | Details | ||
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TARGET -> INHIBITOR |
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TRANSPORTER -> SUBSTRATE |
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BINDER->LIGAND |
The plasma protein to whichSN-38 predominantly binds is albumin.
BINDING
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TRANSPORTER -> INHIBITOR | |||
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CONJUGATE -> TOXIN |
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PRODRUG -> METABOLITE ACTIVE |
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PARENT -> METABOLITE ACTIVE | |||
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PRODRUG -> METABOLITE ACTIVE |
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PRODRUG -> METABOLITE ACTIVE |
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PRODRUG -> METABOLITE ACTIVE |
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PARENT -> IMPURITY |
CHROMATOGRAPHIC PURITY (HPLC/UV)
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ACTIVE MOIETY |
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Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Biological Half-life | PHARMACOKINETIC |
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INTRAVENOUS ADMINISTRATION |
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