559402

SB 218078

A cell-permeable, ATP-competitive, and reversible indolocarbazole derivative that acts as a potent and selective inhibitor of checkpoint kinase (Chk1) in vitro. It inhibits Chk1 phosphorylation of cdc25C with an IC₅₀ of 15 nM.

• Synonym(s): SB 218078, 9,10,11,12,-Tetrahydro-9,12-epoxy-1 H-diindolo(1,2,3-fg:3ʹ,2ʹ,1ʹ-kl)pyrrolo(3,4-i)(1,6)benzodiazocine-1,3(2 H)-dione, Chk1 Inhibitor I, 9,10,11,12,-Tetrahydro-9,12-epoxy-1H-diindolo(1,2,3-fg:3ʹ,2ʹ,1ʹ-kl)pyrrolo(3,4-i)(1,6)benzodiazocine-1,3(2H)-dione, Chk1 Inhibitor I
• Empirical Formula (Hill Notation): C₂₄H₁₅N₃O₃
• CAS Number: 135897-06-2
• Molecular Weight: 393.39
• UNSPSC Code: 12352200

Properties

• Quality Level: 100
• assay: ≥90% (HPLC)
• form: solid
• manufacturer/tradename: Calbiochem^®
• storage condition: OK to freeze; protect from light
• color: yellow
• solubility: DMSO: 20 mg/mL
• shipped in: ambient
• storage temp.: −20°C
• 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)
• InChI key: OTPNDVKVEAIXTI-UHFFFAOYSA-N

Description

General description

A cell-permeable, ATP competitive, and reversible indolocarbazole derivative that acts as a potent inhibitor of checkpoint kinase (Chk1) in vitro (K_i = 15 nM). Binds to the ATP-binding pocket of Chk1, producing only slight changes in the protein conformation. Also inhibits the activity of CDK1 (K_i = 23 nM), CDK2 (K_i = 5.6 nM), and CDK4 (K_i = 16 nM). Inhibits Chk1 phosphorylation of Cdc25C (IC₅₀ = 15 nM).

A cell-permeable, ATP-competitive, and reversible indolocarbazole derivative that acts as a potent and selective inhibitor of checkpoint kinase (Chk1) in vitro. It inhibits Chk1 phosphorylation of cdc25C with an IC₅₀ of 15 nM. However, SB-218078 is a much weaker inhibitor of Cdc2 (IC₅₀ = 250 nM) and PKC (IC₅₀ = 1 µM).

Biochem/physiol Actions

Cell permeable: yes

Primary Target
Chk1

Product competes with ATP.

Reversible: yes

Target IC₅₀: 15 nM against Chk1 phosphorylation of cdc25C; 23 nM, 5.6 nM, 16 nM, against CDK1, CDK2, CDK4, respectively

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

Reconstitution

Following reconstitution aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Other Notes

Zhao, B., et al. 2002. J. Biol. Chem.277, 46609.
Jackson, J.R., et al. 2000. Cancer Res.60, 566

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Safety Information

• Storage Class: 11 - Combustible Solids
• wgk_germany: WGK 1
• flash_point_f: Not applicable
• flash_point_c: Not applicable