product name Kobe0065
Description: Kobe0065 is H-Ras-cRaf1 interaction inhibitor which exhibits potent activity to competitively inhibit the binding of H-Ras·GTP to c-Raf-1 RBD with a Ki value of 46 ± 13 μM. Kobe0065 is a compound screened out by an in silico screen method as a potent inhibitor of the Ras–Raf interaction. It showed favorite efficacy to inhibit the binding of M-Ras.GTP and H-Ras.GTP to the Ras-binding domain of c-Raf-1. Kobe0065 also dose-dependently inhibited the binding of H-RasG12V to c-Raf-1 in NIH 3T3 cells with a rough IC50 value of 10 μM. Besides that, 20 μM of Kobe0065 effectively suppressed the phosphorylation of down-stream kinases of Raf, including MEK and ERK. In NIH 3T3 cells transfected with H-rasG12V, Kobe0065 inhibited the colony formation with IC50 value of 0.5 μM.
References: Proc Natl Acad Sci U S A. 2013 May 14;110(20):8182-7.
449.79
Formula
C15H11ClF3N5O4S
CAS No.
436133-68-5
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 89 mg/mL (197.9 mM)
Water: <1 mg/mL
Ethanol: 13 mg/mL (28.9 mM)
Solubility (In vivo)
Synonyms
other peoduct :
| In Vitro |
In vitro activity: Kobe0065-family compounds bind to Ras⋅GTP and exhibit antiproliferative activity toward cancer cells carrying the activated ras oncogenes. The compounds efficiently inhibit the interaction of Ras⋅GTP with their multiple effectors including Raf, PI3K, and RalGDS and a regulator/effector Sos and show rather broad binding specificity toward various Ras family small GTPases, which may account for their higher potency at the cellular level compared with that of the in vitro binding inhibition. Kinase Assay: Cell Assay: NIH 3T3 cells are transfected with pEF-BOS-HA-H-Ras(G12V) or an empty vector and treated with the 2 and 20 μM compound or the vehicle (DMSO) in the presence of 2% FBS for 1 h. Cell lysate is subjected to detection of c-Raf-1 coimmunoprecipitated with an anti-H-Ras antibody and total c-Raf-1 by Western blotting with an anti-c-Raf-1 antibody. Immunoprecipitated H-Ras(G12V) are detected by an anti-HA antibody. |
|---|---|
| In Vivo | Kobe0065 has antitumor activity. The compound-treated tumors show a prominent increase of apoptotic cells without any significant body weight loss |
| Animal model | A xenograft of SW480 cells in nude mice. |
| Formulation & Dosage | Formulated in Cremophor:ethanol:water (1:1:6); 80 mg/kg and 160 mg/kg; oral administration |
| References | Proc Natl Acad Sci U S A. 2013 May 14;110(20):8182-7. |
