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=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
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
PubMed
| Title | Date | PubMed |
|---|---|---|
| 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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| 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 |
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| Potential interactions between irinotecan and rifampin in a patient with small-cell lung cancer. | 2004 Jun |
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| Phytoestrogens/flavonoids reverse breast cancer resistance protein/ABCG2-mediated multidrug resistance. | 2004 Jun 15 |
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| A phase I trial of pharmacologic modulation of irinotecan with cyclosporine and phenobarbital. | 2004 Nov |
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| Establishment of a 7-ethyl-10-hydroxy-camptothecin-resistant small cell lung cancer cell line. | 2004 Nov-Dec |
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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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| 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 |
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| A randomised phase II multicentre trial of irinotecan (CPT-11) using four different schedules in patients with metastatic colorectal cancer. | 2004 Oct 18 |
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| Enhanced therapeutic efficacy of a novel liposome-based formulation of SN-38 against human tumor models in SCID mice. | 2004 Sep |
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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 |
|
| 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 |
|
| 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 |
|
| 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 |
|
| 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 |
|
| 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 |
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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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| Secretory transport of irinotecan metabolite SN-38 across isolated intestinal tissue. | 2005 May |
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| 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 |
|
| Three-week schedule of irinotecan plus cisplatin in patients with previously untreated extensive-stage small-cell lung cancer. | 2006 Dec 18 |
|
| The novel UGT1A9 intronic I399 polymorphism appears as a predictor of 7-ethyl-10-hydroxycamptothecin glucuronidation levels in the liver. | 2006 Jul |
|
| Phase 1 and pharmacokinetic study of intravenous irinotecan in refractory solid tumor patients with hepatic dysfunction. | 2006 Jun 15 |
|
| Role of ABCG2 as a biomarker for predicting resistance to CPT-11/SN-38 in lung cancer. | 2006 Mar |
|
| 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 |
|
| 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 |
|
| 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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| Radiosensitizers in cervical cancer. Cisplatin and beyond. | 2006 May 8 |
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| A phase II study of FOLFIRI-3 (double infusion of irinotecan combined with LV5FU) after FOLFOX in advanced colorectal cancer patients. | 2006 May 8 |
|
| Effects of green tea compounds on irinotecan metabolism. | 2007 Feb |
|
| 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 |
|
| The contribution of intestinal UDP-glucuronosyltransferases in modulating 7-ethyl-10-hydroxy-camptothecin (SN-38)-induced gastrointestinal toxicity in rats. | 2007 Jan |
|
| 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 |
|
| 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
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
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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)
PRODRUG (METABOLITE ACTIVE)
