SB-218078

SB-218078 is a potent and selective indolocarbazole chk1 inhibitor.

Product information

CAS Number: 135897-06-2

Molecular Weight: 393.39

Formula: C24H15N3O3

Chemical Name:  (5R,8S)-7,8-dihydro-5H-16-oxa-4b,8a,14-triaza-5,8-methanodibenzo[b,h]cycloocta[jkl]cyclopenta[e]-as-indacene-13,15(6H,14H)-dione

Smiles: O=C1NC(=O)C2=C1C1=C3C4=C2C2=CC=CC=C2N4C2CCC(O2)N3C2=CC=CC=C21

InChiKey: OTPNDVKVEAIXTI-UHFFFAOYSA-N

InChi: InChI=1S/C24H15N3O3/c28-23-19-17-11-5-1-3-7-13(11)26-15-9-10-16(30-15)27-14-8-4-2-6-12(14)18(22(27)21(17)26)20(19)24(29)25-23/h1-8,15-16H,9-10H2,(H,25,28,29)

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:

SB-218078 (2.5-5 μM; 18 hours; HeLa cells) treatment abrogates G2 cell cycle arrest caused by either γ-irradiation or a topoisomerase I Topotecan inhibition. SB-218078 (500-625 μM; 96 hours; HeLa and HT-29 cells) treatment significantly increases the cytotoxicity of DNA damage.

In Vivo:

SB-218078 (5 mg/kg; intraperitoneal injection; for 16 hours; C57/Bl6 mice) treatment could promote a strong increase of γ-H2AX and apoptosis throughout the lymphoma, while having no effect on a healthy spleen in Myc-induced lymphomas mouse model.

References:

1. Jennings-Gee J, Pardee TS, Gmeiner WH. Replication-dependent irreversible topoisomerase 1 poisoning is responsible for FdUMP[10] anti-leukemic activity. Exp Hematol. 2013 Feb;41(2):180-188.e4. doi: 10.1016/j.exphem.2012.10.007. Epub 2012 Oct 17. PubMed PMID: 23085462; PubMed Central PMCID: PMC3660094.
2. Park JH, Kim WS, Kim JY, Park MH, Nam JH, Yun CW, Kwon YG, Jo I. Chk1 and Hsp90 cooperatively regulate phosphorylation of endothelial nitric oxide synthase at serine 1179. Free Radic Biol Med. 2011 Dec 15;51(12):2217-26. doi: 10.1016/j.freeradbiomed.2011.09.021. Epub 2011 Sep 25. PubMed PMID: 22001744.
3. Fishler T, Li YY, Wang RH, Kim HS, Sengupta K, Vassilopoulos A, Lahusen T, Xu X, Lee MH, Liu Q, Elledge SJ, Ried T, Deng CX. Genetic instability and mammary tumor formation in mice carrying mammary-specific disruption of Chk1 and p53. Oncogene. 2010 Jul 15;29(28):4007-17. doi: 10.1038/onc.2010.163. Epub 2010 May 17. PubMed PMID: 20473325.
4. Azorsa DO, Gonzales IM, Basu GD, Choudhary A, Arora S, Bisanz KM, Kiefer JA, Henderson MC, Trent JM, Von Hoff DD, Mousses S. Synthetic lethal RNAi screening identifies sensitizing targets for gemcitabine therapy in pancreatic cancer. J Transl Med. 2009 Jun 11;7:43. doi: 10.1186/1479-5876-7-43. PubMed PMID: 19519883; PubMed Central PMCID: PMC2702280.
5. Robles AI, Wright MH, Gandhi B, Feis SS, Hanigan CL, Wiestner A, Varticovski L. Schedule-dependent synergy between the heat shock protein 90 inhibitor 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin and doxorubicin restores apoptosis to p53-mutant lymphoma cell lines. Clin Cancer Res. 2006 Nov 1;12(21):6547-56. PubMed PMID: 17085670.

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