BBO-10203

SKU: orb2814299

Description

BBO-10203 (Compound 758) is an orally bioavailable, selective PI3Kα-Ras interaction disruptor that binds the PI3Kα Ras-binding domain. It blocks complex formation, inhibits downstream Akt signaling without affecting basal PI3Kα activity, and shows selective antitumor efficacy in KRAS-mutant cancer models in vitro and in vivo.

Research Area

Signal Transduction

Key Properties

• CAS Number: 2971769-60-3
• MW: 640.7
• Purity: 99.87%
• Formula: C₃₄H₃₀F₂N₆O₃S
• SMILES: O=C(C=C)N1CCN2N=C(C=C2C1C)C=3N=C(C=4C=CC5=C(C=NN5C)C4)C=6C=CSC6C3C7=C(F)C=C(F)C=C7OCCOC
• Target: Akt,PI3K
• Solubility: DMSO:80 mg/mL (124.86 mM)

Bioactivity

• In Vivo:
  In fasting male mice undergoing an oral glucose tolerance test, 300 mg/kg BBO-10203 did not affect glucose metabolism, while 50 mg/kg aprelis was associated with hyperglycaemia and hyperinsulinaemia. In xenograft mouse models with KRAS G12X mutations, with or without PIK3CA mutations, BBO-10203 (10–100 mg/kg, oral, once daily, for 28 days) exhibited dose-dependent tumour volume reduction effects and antitumour efficacy in several subcutaneous xenograft models with multiple KRAS mutations.
• In Vitro:
  BBO-10203 blocks the interaction between KRAS-G12D and PI3Kα in HEK293T cells with an IC50 of 6 nM, without affecting the binding between KRAS-G12D and protein kinase CRAF or inhibiting the in vitro kinase activity of PI3Kα. BBO-10203 exhibits an IC50 < 10 nM against most HER2 gene-amplified cell lines and is sensitive to PIK3CA spiral mutations in cell lines.

Storage & Handling

• Storage: store at low temperature | 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

BBO10203

Compound Identifiers

PubChem CID

169136372