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
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/23928356 | https://www.ncbi.nlm.nih.gov/pubmed/27108266https://www.ncbi.nlm.nih.gov/pubmed/21630281 | https://clinicaltrials.gov/ct2/show/NCT00385177 | http://getfilings.com/sec-filings/100308/ONCOGENEX-PHARMACEUTICALS-INC_10-K/Curator'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/23928356 | https://www.ncbi.nlm.nih.gov/pubmed/27108266https://www.ncbi.nlm.nih.gov/pubmed/21630281 | https://clinicaltrials.gov/ct2/show/NCT00385177 | http://getfilings.com/sec-filings/100308/ONCOGENEX-PHARMACEUTICALS-INC_10-K/
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/1651156
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.
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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Apoptosis induced by culturing MH134 cells in the presence of porcine skin gelatin in vitro. | 2002 Aug |
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Irinotecan pharmacokinetics-pharmacodynamics: the clinical relevance of prolonged exposure to SN-38. | 2002 Jul 15 |
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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 |
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Clinical pharmacokinetics of irinotecan and its metabolites in relation with diarrhea. | 2002 Sep |
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Common human UGT1A polymorphisms and the altered metabolism of irinotecan active metabolite 7-ethyl-10-hydroxycamptothecin (SN-38). | 2002 Sep |
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Functional characterization of human UDP-glucuronosyltransferase 1A9 variant, D256N, found in Japanese cancer patients. | 2003 Aug |
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Phase I clinical and pharmacokinetic study of irinotecan in adults with recurrent malignant glioma. | 2003 Aug 1 |
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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 |
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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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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 |
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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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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 |
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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 |
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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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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 |
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Phase I and pharmacokinetic study of irinotecan in combination with R115777, a farnesyl protein transferase inhibitor. | 2004 Apr 19 |
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Characterization of inhibitors of specific carboxylesterases: development of carboxylesterase inhibitors for translational application. | 2004 Aug |
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Pharmacogenetics of human carboxylesterase 2, an enzyme involved in the activation of irinotecan into SN-38. | 2004 Dec |
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Development and characterization of a novel liposome-based formulation of SN-38. | 2004 Feb 11 |
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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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Laminin-5 offsets the efficacy of gefitinib ('Iressa') in hepatocellular carcinoma cells. | 2004 Nov 29 |
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Identification of the cytosolic carboxylesterase catalyzing the 5'-deoxy-5-fluorocytidine formation from capecitabine in human liver. | 2004 Oct |
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Gefitinib reverses breast cancer resistance protein-mediated drug resistance. | 2004 Sep |
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ABCG2 pharmacogenetics: ethnic differences in allele frequency and assessment of influence on irinotecan disposition. | 2004 Sep 1 |
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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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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 |
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Estrogen-mediated post transcriptional down-regulation of breast cancer resistance protein/ABCG2. | 2005 Jan 15 |
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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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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 |
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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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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 |
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A phase I clinical and pharmacokinetic study of capecitabine (Xeloda) and irinotecan combination therapy (XELIRI) in patients with metastatic gastrointestinal tumours. | 2005 Mar 14 |
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Methylseleninic acid potentiates apoptosis induced by chemotherapeutic drugs in androgen-independent prostate cancer cells. | 2005 Mar 15 |
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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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Effect of milk thistle (Silybum marianum) on the pharmacokinetics of irinotecan. | 2005 Nov 1 |
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Glucuronidation of trans-resveratrol by human liver and intestinal microsomes and UGT isoforms. | 2006 Apr |
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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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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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Functional SNPs of the breast cancer resistance protein-therapeutic effects and inhibitor development. | 2006 Mar 8 |
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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 |
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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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A phase II study of biweekly dose-intensified oral capecitabine plus irinotecan (bXELIRI) for patients with advanced or metastatic gastric cancer. | 2007 May 21 |
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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
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
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FDA ORPHAN DRUG |
840021
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FDA ORPHAN DRUG |
513715
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86639-52-3
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104842
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0H43101T0J
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SUB188424
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C61618
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1347631
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DB05482
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100000174485
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8988
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SN-38
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DTXSID4040399
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ACTIVE MOIETY
PARENT (METABOLITE ACTIVE)
PRODRUG (METABOLITE ACTIVE)
PRODRUG (METABOLITE ACTIVE)
PRODRUG (METABOLITE ACTIVE)
PRODRUG (METABOLITE ACTIVE)