SB218078

SB-218078 is a potent, selective and cell-permeable checkpoint kinase 1 (Chk1) inhibitor that inhibits Chk1 phosphorylation of cdc25C with an IC50 of 15 nM. SB-218078 is less potently inhibits Cdc2 (IC50 of 250 nM) and PKC (IC50 of 1000 nM). SB-218078 causes apoptosis by DNA damage and cell cycle arrest[1][2][3].

Signaling Pathways >> Epigenetics >> PKC

Research Areas >> Cancer

Signaling Pathways >> Cell Cycle/DNA Damage >> Checkpoint Kinase (Chk)

Signaling Pathways >> Cell Cycle/DNA Damage >> CDK

Signaling Pathways >> TGF-beta/Smad >> PKC

Chk1:15 nM (IC50)

Cdc2:250 nM (IC50)

PKC:1000 nM (IC50)

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[1]. SB-218078 (500-625 μM; 96 hours; HeLa and HT-29 cells) treatment significantly increases the cytotoxicity of DNA damage [1]. Cell Cycle Analysis[1] Cell Line: HeLa cells Concentration: 2.5 μM, 5 μM Incubation Time: 18 hours Result: Abrogated G2 cell cycle arrest caused by γ-irradiation and topoisomerase I inhibition. Cell Cytotoxicity Assay[1] Cell Line: HeLa and HT-29 cells Concentration: 500 nM, 625 nM Incubation Time: 96 hours Result: Enhanced cytotoxicity of DNA damage.

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[2]. Animal Model: C57/Bl6 mice injected with ARF-/- lymphomas[2] Dosage: 5 mg/kg Administration: Intraperitoneal injection; for 16 hours Result: Promoted a strong increase of γ-H2AX and apoptosis throughout the lymphoma.

[1]. Jackson JR, et al. An indolocarbazole inhibitor of human checkpoint kinase (Chk1) abrogates cell cycle arrest caused by DNA damage. Cancer Res. 2000 Feb 1;60(3):566-72.

[2]. Murga M, et al. Exploiting oncogene-induced replicative stress for the selective killing of Myc-driven tumors. Nat Struct Mol Biol. 2011 Nov 27;18(12):1331-1335.

[3]. Preet R, et al. Chk1 inhibitor synergizes quinacrine mediated apoptosis in breast cancer cells by compromising the base excision repair cascade. Biochem Pharmacol. 2016 Apr 1;105:23-33.