SN-38

• CAT Number: I005211
• CAS Number: 86639-52-3
• Molecular Formula: C22H20N2O5
• Molecular Weight: 392.4
• Purity: ≥95%
• Target: topoisomerase I
• Solubility: DMSO: ≥ 40 mg/mL
• Storage: 3 years -20C powder
• InChI: 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
• InChIKey: FJHBVJOVLFPMQE-QFIPXVFZSA-N
• SMILES: O=C([C@]1(O)CC)OCC2=C1C=C(C(N=C(C=CC(O)=C3)C3=C4CC)=C4C5)N5C2=O

SN-38 (CAT: I005211) is an active metabolite of the chemotherapeutic drug irinotecan. It is formed through the enzymatic conversion of irinotecan by carboxylesterases in the body. SN-38 exerts its pharmacologic action as a potent topoisomerase I inhibitor. It stabilizes the cleavable complex formed by topoisomerase I and DNA, leading to the inhibition of DNA replication and transcription, ultimately resulting in DNA damage and cell death. SN-38 is highly cytotoxic and has demonstrated efficacy against various cancers, including colorectal cancer.

Reference

1:Targeted drug distribution in tumor extracellular fluid of GD2-expressing neuroblastoma patient-derived xenografts using SN-38-loaded nanoparticles conjugated to the monoclonal antibody 3F8. Monterrubio C, Paco S, Olaciregui NG, Pascual-Pasto G, Vila-Ubach M, Cuadrado-Vilanova M, Ferrandiz MM, Castillo-Ecija H, Glisoni R, Kuplennik N, Jungbluth A, de Torres C, Lavarino C, Cheung NV, Mora J, Sosnik A, Carcaboso AM.J Control Release. 2017 Apr 12;255:108-119. doi: 10.1016/j.jconrel.2017.04.016. [Epub ahead of print] PMID: 28412222 2:Determination of irinotecan, SN-38 and SN-38 glucuronide using HPLC/MS/MS: Application in a clinical pharmacokinetic and personalized medicine in colorectal cancer patients. Atasilp C, Chansriwong P, Sirachainan E, Reungwetwattana T, Puangpetch A, Prommas S, Sirilerttrakul S, Rerkarmnuaychoke B, Wongwaisayawan S, Sukasem C.J Clin Lab Anal. 2017 Apr 10. doi: 10.1002/jcla.22217. [Epub ahead of print] PMID: 28393405 3:Synthesis and biological evaluation of hypoxia-activated prodrugs of SN-38. Jin C, Zhang Q, Lu W.Eur J Med Chem. 2017 May 26;132:135-141. doi: 10.1016/j.ejmech.2017.03.040. Epub 2017 Mar 22. PMID: 28350997 4:Cooperative inhibitory effects of uremic toxins and other serum components on OATP1B1-mediated transport of SN-38. Katsube Y, Tsujimoto M, Koide H, Ochiai M, Hojyo A, Ogawa K, Kambara K, Torii N, Shima D, Furukubo T, Izumi S, Yamakawa T, Minegaki T, Nishiguchi K.Cancer Chemother Pharmacol. 2017 Apr;79(4):783-789. doi: 10.1007/s00280-017-3276-y. Epub 2017 Mar 17. PMID: 28314987 5:Correlative analysis of plasma SN-38 levels and DPD activity with outcomes of FOLFIRI regimen for metastatic colorectal cancer with UGT1A1 *28 and *6 wild type and its implication for individualized chemotherapy. Cai X, Tian C, Wang L, Zhuang R, Zhang X, Guo Y, Lu H, Wang H, Li X, Gao J, Li Q, Wang C.Cancer Biol Ther. 2017 Mar 4;18(3):186-193. doi: 10.1080/15384047.2017.1294286. Epub 2017 Feb 17. PMID: 28278081 6:Combined use of irinotecan with histone deacetylase inhibitor belinostat could cause severe toxicity by inhibiting SN-38 glucuronidation via UGT1A1. Wang L, Chan CE, Wong AL, Wong FC, Lim SW, Chinnathambi A, Alharbi SA, Lee LS, Soo R, Yong WP, Lee SC, Ho PC, Sethi G, Goh BC.Oncotarget. 2017 Feb 1. doi: 10.18632/oncotarget.15017. [Epub ahead of print] PMID: 28157715 Free Article7:CQ synergistically sensitizes human colorectal cancer cells to SN-38/CPT-11 through lysosomal and mitochondrial apoptotic pathway via p53-ROS cross-talk. Chen P, Luo X, Nie P, Wu B, Xu W, Shi X, Chang H, Li B, Yu X, Zou Z.Free Radic Biol Med. 2017 Mar;104:280-297. doi: 10.1016/j.freeradbiomed.2017.01.033. Epub 2017 Jan 25. PMID: 28131902 8:Synthetic Lethality Exploitation by an Anti-Trop-2-SN-38 Antibody-Drug Conjugate, IMMU-132, Plus PARP Inhibitors in BRCA1/2-wild-type Triple-Negative Breast Cancer. Cardillo TM, Sharkey RM, Rossi DL, Arrojo R, Mostafa AA, Goldenberg DM.Clin Cancer Res. 2017 Jan 9. doi: 10.1158/1078-0432.CCR-16-2401. [Epub ahead of print] PMID: 28069724 9:Tumour regression and improved gastrointestinal tolerability from controlled release of SN-38 from novel polyoxazoline-modified dendrimers. England RM, Hare JI, Barnes J, Wilson J, Smith A, Strittmatter N, Kemmitt PD, Waring MJ, Barry ST, Alexander C, Ashford MB.J Control Release. 2017 Feb 10;247:73-85. doi: 10.1016/j.jconrel.2016.12.034. Epub 2016 Dec 30. PMID: 28043863 10:Intraarterial Therapy Using Micellar Nanoparticles Incorporating SN-38 in a Rabbit Liver Tumor Model. Nishiofuku H, Tanaka T, Fukuoka Y, Sato T, Masada T, Tatsumoto S, Sho M, Yamato I, Yasuda S, Matsushima S, Takano M, Ohbayashi C, Kichikawa K.J Vasc Interv Radiol. 2017 Mar;28(3):457-464. doi: 10.1016/j.jvir.2016.10.032. Epub 2016 Dec 29. PMID: 28041782