SN-38
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MedKoo CAT#: 406280

CAS#: 86639-52-3

Description: SN-38 is the active metabolite of irinotecan (an analog of camptothecin - a topoisomerase I inhibitor); it is 1000 times more active than irinotecan itself. In vitro cytotoxicity assays show that the potency of SN-38 relative to irinotecan varies from 2- to 2000-fold. SN38 is metabolized via glucoronidation by UGT1A1. The variant of UGT1A1 in ~10% of Caucasians which leads to poor metabolization of irinotecan predicts irinotecan toxicity, as it cannot be excreted from the body in its SN-38 form. SN-38 is lost into the bile and feces. It can cause the symptoms of diarrhoea and myelosuppression experienced by ~25% of the patients administered irinotecan.


Chemical Structure

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SN-38
CAS# 86639-52-3

Theoretical Analysis

MedKoo Cat#: 406280
Name: SN-38
CAS#: 86639-52-3
Chemical Formula: C22H20N2O5
Exact Mass: 392.13722
Molecular Weight: 392.4
Elemental Analysis: C, 67.34; H, 5.14; N, 7.14; O, 20.39

Price and Availability

Size Price Availability Quantity
100.0mg USD 90.0 Ready to ship
500.0mg USD 150.0 Ready to ship
1.0g USD 250.0 Ready to ship
2.0g USD 450.0 Ready to ship
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Synonym: SN38; SN-38; SN 38; 10-hydroxy-7-ethylcamptothecin; irinotecan metabolite.

IUPAC/Chemical Name: (S)-4,11-diethyl-4,9-dihydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione

InChi Key: FJHBVJOVLFPMQE-QFIPXVFZSA-N

InChi Code: 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

SMILES Code: O=C1[C@](O)(CC)C2=C(CO1)C(N3CC4=C(CC)C5=CC(O)=CC=C5N=C4C3=C2)=O

Appearance: Light yellow solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Biological target: SN-38 (NK012) inhibits DNA and RNA synthesis with IC50s of 0.077 and 1.3 μM, respectively.
In vitro activity: SN-38, the active metabolite of the Top I inhibitor irinotecan, and TLR4 (toll-like receptor 4) interaction was assessed using the in vitro luciferase nuclear factor-κB reporter assay, neutrophil migration to murine air-pouch, in silico simulation, and the thermal shift assay (TSA). Non-cytotoxic concentrations of SN-38 attenuated LPS (a TLR4 agonist)-driven cell activation without affecting peptidoglycan (a TLR2 agonist)-activating response. Conversely, increasing concentrations of LPS reversed the SN-38 inhibitory effect. In addition, SN-38 abrogated LPS-dependent neutrophil migration and reduced TNF-α, IL-6, and keratinocyte chemoattractant levels in the air-pouch model, but failed to inhibit zymosan (a TLR2 agonist)-induced cell migration. A two-step molecular docking analysis indicated two potential binding sites for the SN-38 in the MD-2/TLR4 complex, the hydrophobic MD-2 pocket (binding energy of - 8.1 kcal/mol) and the rim of the same molecule (- 6.9 kcal/mol). Furthermore, the TSA suggested the interaction of SN-38 with MD-2. Reference: Cancer Chemother Pharmacol. 2019 Aug;84(2):287-298. https://link.springer.com/article/10.1007%2Fs00280-019-03844-z
In vivo activity: Wistar rats are used to study the anatomic and functional impact of electrospun nanofiber matrices eluting SN-38-a potent chemotherapeutic agent-on several body sites where pediatric tumors such as neuroblastoma, Ewing sarcoma, and rhabdomyosarcoma arise. Blank and SN-38-loaded matrices embracing the femoral neurovascular bundle or in direct contact with abdominal viscera (liver, kidney, urinary bladder, intestine, and uterus) are placed. Foreign body tissue reaction to the implants is observed though no histologic damage in any tissue/organ. Skin healing is normal. Tissue reaction is similar for SN-38-loaded and blank matrices, with the exception of the hepatic capsule that is thicker for the former although within the limits consistent with mild foreign body reaction. Tissue and organ function is completely conserved after local treatments, as assessed by the rotarod test (forelimb function), hematologic tests (liver and renal function), and control of clinical signs. Overall, these findings support the clinical translation of SN-38-loaded nanofiber matrices to improve local control strategies of surgically resected tumors. Reference: Adv Healthc Mater. 2018 Aug;7(15):e1800255. https://onlinelibrary.wiley.com/doi/abs/10.1002/adhm.201800255

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 24.16 61.57
DMSO:PBS (pH 7.2) (1:2) 0.3 0.76
DMF 0.1 0.25

Preparing Stock Solutions

The following data is based on the product molecular weight 392.4 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Wong DVT, Ribeiro-Filho HV, Wanderley CWS, Leite CAVG, Lima JB, Assef ANB, Cajado AG, Batista GLP, González RH, Silva KO, Borges LPC, Alencar NMN, Wilke DV, Cunha TM, Figueira ACM, Cunha FQ, Lima-Júnior RCP. SN-38, the active metabolite of irinotecan, inhibits the acute inflammatory response by targeting toll-like receptor 4. Cancer Chemother Pharmacol. 2019 Aug;84(2):287-298. doi: 10.1007/s00280-019-03844-z. Epub 2019 Apr 22. PMID: 31011814. 2. Manzanares A, Restrepo-Perdomo CA, Botteri G, Castillo-Ecija H, Pascual-Pasto G, Cano F, Garcia-Alvarez L, Monterrubio C, Ruiz B, Vazquez-Carrera M, Suñol M, Mora J, Tornero JA, Sosnik A, Carcaboso AM. Tissue Compatibility of SN-38-Loaded Anticancer Nanofiber Matrices. Adv Healthc Mater. 2018 Aug;7(15):e1800255. doi: 10.1002/adhm.201800255. Epub 2018 Jun 11. PMID: 29892999.
In vitro protocol: 1. Wong DVT, Ribeiro-Filho HV, Wanderley CWS, Leite CAVG, Lima JB, Assef ANB, Cajado AG, Batista GLP, González RH, Silva KO, Borges LPC, Alencar NMN, Wilke DV, Cunha TM, Figueira ACM, Cunha FQ, Lima-Júnior RCP. SN-38, the active metabolite of irinotecan, inhibits the acute inflammatory response by targeting toll-like receptor 4. Cancer Chemother Pharmacol. 2019 Aug;84(2):287-298. doi: 10.1007/s00280-019-03844-z. Epub 2019 Apr 22. PMID: 31011814.
In vivo protocol: 1. Manzanares A, Restrepo-Perdomo CA, Botteri G, Castillo-Ecija H, Pascual-Pasto G, Cano F, Garcia-Alvarez L, Monterrubio C, Ruiz B, Vazquez-Carrera M, Suñol M, Mora J, Tornero JA, Sosnik A, Carcaboso AM. Tissue Compatibility of SN-38-Loaded Anticancer Nanofiber Matrices. Adv Healthc Mater. 2018 Aug;7(15):e1800255. doi: 10.1002/adhm.201800255. Epub 2018 Jun 11. PMID: 29892999.

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1. Yang Y, Wu ZX, Wang JQ, Teng QX, Lei ZN, Lusvarghi S, Ambudkar SV, Chen ZS, Yang DH. OTS964, a TOPK Inhibitor, Is Susceptible to ABCG2-Mediated Drug Resistance. Front Pharmacol. 2021 Feb 15;12:620874. doi: 10.3389/fphar.2021.620874. PMID: 33658942; PMCID: PMC7917255.

1: Buck A, Halbritter S, Späth C, Feuchtinger A, Aichler M, Zitzelsberger H, Janssen KP, Walch A. Distribution and quantification of irinotecan and its active metabolite SN-38 in colon cancer murine model systems using MALDI MSI. Anal Bioanal Chem. 2014 Oct 14. [Epub ahead of print] PubMed PMID: 25311193.

2: Yang FY, Zhang WP, Wang XY, Yang WC, Dang HW. [Pharmacokinetics of SN-38 in rats and tissue distribution of 7-ethyl-10-hydroxycamptothecin in mice after intravenous injection of irinotecan hydrochloride nanoparticles]. Yao Xue Xue Bao. 2014 Jul;49(7):1029-33. Chinese. PubMed PMID: 25233635.

3: Minami K, Kamijo Y, Nishizawa Y, Tabata S, Horikuchi F, Yamamoto M, Kawahara K, Shinsato Y, Tachiwada T, Chen ZS, Tsujikawa K, Nakagawa M, Seki N, Akiyama S, Arima K, Takeda Y, Furukawa T. Expression of ABCB6 is related to resistance to 5-FU, SN-38 and vincristine. Anticancer Res. 2014 Sep;34(9):4767-73. PubMed PMID: 25202056.

4: Ghazaly E, Perry J, Kitromilidou C, Powles T, Joel S. Development and validation of an ultra-high performance LC-MS/MS assay for intracellular SN-38 in human solid tumour cell lines: comparison with a validated HPLC-fluorescence method. J Chromatogr B Analyt Technol Biomed Life Sci. 2014 Oct 15;969:213-8. doi: 10.1016/j.jchromb.2014.08.024. Epub 2014 Aug 27. PubMed PMID: 25195021.

5: Hu T, Chung YM, Guan M, Ma M, Ma J, Berek JS, Hu MC. Reprogramming ovarian and breast cancer cells into non-cancerous cells by low-dose metformin or SN-38 through FOXO3 activation. Sci Rep. 2014 Jul 24;4:5810. doi: 10.1038/srep05810. PubMed PMID: 25056111; PubMed Central PMCID: PMC4108946.

6: Nittayacharn P, Manaspon C, Hongeng S, Nasongkla N. HPLC analysis and extraction method of SN-38 in brain tumor model after injected by polymeric drug delivery system. Exp Biol Med (Maywood). 2014 Jul 2. pii: 1535370214539227. [Epub ahead of print] PubMed PMID: 24990485.

7: Park DJ, Won JH, Cho AR, Yun HJ, Heo JH, Hwhang TH, Lee DH, Kim WM. Determination of irinotecan and its metabolite SN-38 in rabbit plasma and tumors using a validated method of tandem mass spectrometry coupled with liquid chromatography. J Chromatogr B Analyt Technol Biomed Life Sci. 2014 Jul 1;962:147-52. doi: 10.1016/j.jchromb.2014.05.042. Epub 2014 May 27. PubMed PMID: 24927278.

8: Wang H, Bian T, Jin T, Chen Y, Lin A, Chen C. Association analysis of UGT1A genotype and haplotype with SN-38 glucuronidation in human livers. Pharmacogenomics. 2014 Apr;15(6):785-98. doi: 10.2217/pgs.14.29. PubMed PMID: 24897286.

9: Yu J, Han JC, Gao YJ. Biotransformation of Glucoaurantio-Obtusin Towards Aurantio-Obtusin Increases the Toxicity of Irinotecan Through Increased Inhibition Towards SN-38 Glucuronidation. Phytother Res. 2014 Oct;28(10):1577-80. doi: 10.1002/ptr.5162. Epub 2014 May 19. PubMed PMID: 24842785.

10: Chu C, Abbara C, Tandia M, Polrot M, Gonin P, Farinotti R, Bonhomme-Faivre L. Cetuximab increases concentrations of irinotecan and of its active metabolite SN-38 in plasma and tumour of human colorectal carcinoma-bearing mice. Fundam Clin Pharmacol. 2014 Mar 3. doi: 10.1111/fcp.12071. [Epub ahead of print] PubMed PMID: 24588516.

11: Tahara M, Inoue T, Sato F, Miyakura Y, Horie H, Yasuda Y, Fujii H, Kotake K, Sugano K. The use of Olaparib (AZD2281) potentiates SN-38 cytotoxicity in colon cancer cells by indirect inhibition of Rad51-mediated repair of DNA double-strand breaks. Mol Cancer Ther. 2014 May;13(5):1170-80. doi: 10.1158/1535-7163.MCT-13-0683. Epub 2014 Feb 27. PubMed PMID: 24577941.

12: Santi DV, Schneider EL, Ashley GW. Macromolecular prodrug that provides the irinotecan (CPT-11) active-metabolite SN-38 with ultralong half-life, low C(max), and low glucuronide formation. J Med Chem. 2014 Mar 27;57(6):2303-14. doi: 10.1021/jm401644v. Epub 2014 Mar 6. PubMed PMID: 24494988.

13: Yanagihara K, Takigahira M, Kubo T, Ochiya T, Hamaguchi T, Matsumura Y. Marked antitumor effect of NK012, a SN-38-incorporating micelle formulation, in a newly developed mouse model of liver metastasis resulting from gastric cancer. Ther Deliv. 2014 Feb;5(2):129-38. doi: 10.4155/tde.13.143. PubMed PMID: 24483192.

14: Vangara KK, Ali HI, Lu D, Liu JL, Kolluru S, Palakurthi S. SN-38-cyclodextrin complexation and its influence on the solubility, stability, and in vitro anticancer activity against ovarian cancer. AAPS PharmSciTech. 2014 Apr;15(2):472-82. doi: 10.1208/s12249-013-0068-5. Epub 2014 Jan 30. PubMed PMID: 24477982; PubMed Central PMCID: PMC3969487.

15: Jeong W, Park SR, Rapisarda A, Fer N, Kinders RJ, Chen A, Melillo G, Turkbey B, Steinberg SM, Choyke P, Doroshow JH, Kummar S. Weekly EZN-2208 (PEGylated SN-38) in combination with bevacizumab in patients with refractory solid tumors. Invest New Drugs. 2014 Apr;32(2):340-6. doi: 10.1007/s10637-013-0048-3. Epub 2013 Nov 16. PubMed PMID: 24242862.

16: Iusuf D, Ludwig M, Elbatsh A, van Esch A, van de Steeg E, Wagenaar E, van der Valk M, Lin F, van Tellingen O, Schinkel AH. OATP1A/1B transporters affect irinotecan and SN-38 pharmacokinetics and carboxylesterase expression in knockout and humanized transgenic mice. Mol Cancer Ther. 2014 Feb;13(2):492-503. doi: 10.1158/1535-7163.MCT-13-0541. Epub 2013 Nov 5. PubMed PMID: 24194565.

17: Garrett CR, Bekaii-Saab TS, Ryan T, Fisher GA, Clive S, Kavan P, Shacham-Shmueli E, Buchbinder A, Goldberg RM. Randomized phase 2 study of pegylated SN-38 (EZN-2208) or irinotecan plus cetuximab in patients with advanced colorectal cancer. Cancer. 2013 Dec 15;119(24):4223-30. doi: 10.1002/cncr.28358. Epub 2013 Sep 16. PubMed PMID: 24105075.

18: Satoh T, Yasui H, Muro K, Komatsu Y, Sameshima S, Yamaguchi K, Sugihara K. Pharmacokinetic assessment of irinotecan, SN-38, and SN-38-glucuronide: a substudy of the FIRIS study. Anticancer Res. 2013 Sep;33(9):3845-53. PubMed PMID: 24023318.

19: Lee PC, Chiou YC, Wong JM, Peng CL, Shieh MJ. Targeting colorectal cancer cells with single-walled carbon nanotubes conjugated to anticancer agent SN-38 and EGFR antibody. Biomaterials. 2013 Nov;34(34):8756-65. doi: 10.1016/j.biomaterials.2013.07.067. Epub 2013 Aug 12. PubMed PMID: 23937913.

20: Fujita K, Sugiura T, Okumura H, Umeda S, Nakamichi N, Watanabe Y, Suzuki H, Sunakawa Y, Shimada K, Kawara K, Sasaki Y, Kato Y. Direct inhibition and down-regulation by uremic plasma components of hepatic uptake transporter for SN-38, an active metabolite of irinotecan, in humans. Pharm Res. 2014 Jan;31(1):204-15. doi: 10.1007/s11095-013-1153-x. Epub 2013 Aug 7. PubMed PMID: 23921491.

SN-38

100.0mg / USD 90.0


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