Kobe0065

SKU: orb1307283

Description

Kobe0065 is a novel small-molecule inhibitor of the Ras-Raf interaction, developed through structure-based drug design. It competitively inhibits H-Ras·GTP binding to c-Raf-1 RBD with a Ki of 46 ± 13 µM, making it a useful tool for in vitro studies of MAPK/ERK pathway signaling and oncogenic Ras function.

Research Area

Cell Biology, Pharmacology & Drug Discovery, Signal Transduction

Key Properties

• CAS Number: 436133-68-5
• MW: 449.79
• Purity: 100.00%
• Formula: C₁₅H₁₁ClF₃N₅O₄S
• SMILES: Cc1ccc(NC(=S)NNc2c(cc(cc2[N+]([O-])=O)C(F)(F)F)[N+]([O-])=O)cc1Cl
• Target: Apoptosis,Raf,Ras
• Solubility: DMSO:20 mg/mL (44.47 mM);Ethanol:4.5 mg/mL (10 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (4.45 mM)

Bioactivity

• Target IC50:
  C-Raf1 RBD:46 ± 13 μM(ki)
• In Vivo:
  Kobe0065 has antitumor activity. The compound-treated tumors show a prominent increase of apoptotic cells without any significant body weight loss.
• In Vitro:
  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.
• Cell Research:
  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.(Only for Reference)

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Inhibitor, Kobe 0065, Kobe0065, Kobe-0065, inhibit, Apoptosis, Ras-Raf, Ras

Compound Identifiers

PubChem CID

3827663