SW-044248. CAS# 522650-83-5

SW-044248, CAS No. 522650-83-5, is a potent and selective Topoisomerase I inhibitor. SW044248 killed approximately 15% of a panel of 74 NSCLC cell lines and was nontoxic to immortalized human bronchial cell lines. The acute transcriptional response to SW044248 in sensitive HCC4017 cells correlated significantly with inhibitors of topoisomerases and SW044248 inhibited topoisomerase 1 (Top1) but not topoisomerase 2. SW044248 inhibited Top1 differently from camptothecin and camptothecin did not show the same selective toxicity as SW044248. Elimination of Top1 by siRNA partially protected cells from SW044248, although removing Top1 was itself eventually toxic.

Product information

CAS Number: 522650-83-5

Molecular Weight: 421.52

Formula: C22H23N5O2S

Synonym:

SW044248

SW-044248

SW 044248

Chemical Name: 2-((5-ethyl-5H-[1,2,4]triazino[5,6-b]indol-3-yl)thio)-N-(2-methoxyphenyl)butanamide

Smiles: COC1=CC=CC=C1NC(=O)C(CC)SC1=NC2=C(N=N1)C1=CC=CC=C1N2CC

InChiKey: PEVRGVRHMMZNGI-UHFFFAOYSA-N

InChi: InChI=1S/C22H23N5O2S/c1-4-18(21(28)23-15-11-7-9-13-17(15)29-3)30-22-24-20-19(25-26-22)14-10-6-8-12-16(14)27(20)5-2/h6-13,18H,4-5H2,1-3H3,(H,23,28)

Technical Data

Appearance: Solid Power.

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

Solubility: Soluble in DMSO, not in water

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

SW044248 is a non-canonical Top1 inhibitor, and is selectively toxic for certain NSCLC cell lines. SW044248 shows no effect on Top2. SW044248 (2, 5, 10 μM) rapidly inhibits transcription, translation and DNA synthesis in sensitive cells (HCC4017 and H292 cells) but not insensitive cells (HBEC30KT cells and HCC44 cells). SW044248 (10 μM) rapidly activates the integrated stress response through kinases GCN2 and PKR. The inhibition of Top1 in HCC4017 cells is helpful to the toxicity of SW044248. SW044248 (5, 10 μM) shows no effect on HBEC30KT and HCC44 cell lines due to the up-regulation of p21CDKN1A. SW044248 is selectively toxic in 18/74 NSCLC lines.

References:

1. Zubovych IO, Sethi A, Kulkarni A, Tagal V, Roth MG. A Novel Inhibitor of Topoisomerase I Is Selectively Toxic for a Subset of Non-Small Cell Lung Cancer Cell Lines. Mol Cancer Ther. 2016 Jan;15(1):23-36. doi: 10.1158/1535-7163.MCT-15-0458. Epub 2015 Dec 14. PubMed PMID: 26668189; PubMed Central PMCID: PMC4707128.
2. Kim HS, Mendiratta S, Kim J, Pecot CV, Larsen JE, Zubovych I, Seo BY, Kim J, Eskiocak B, Chung H, McMillan E, Wu S, De Brabander J, Komurov K, Toombs JE, Wei S, Peyton M, Williams N, Gazdar AF, Posner BA, Brekken RA, Sood AK, Deberardinis RJ, Roth MG, Minna JD, White MA. Systematic identification of molecular subtype-selective vulnerabilities in non-small-cell lung cancer. Cell. 2013 Oct 24;155(3):552-66. doi: 10.1016/j.cell.2013.09.041. Epub 2013 Oct 24. PubMed PMID: 24243015; PubMed Central PMCID: PMC3836195.

Products are for research use only. Not for human use.