VVD-699 is a covalent blocker of the RAS-p110α interaction with oral activity. VVD-699 inhibits activation of PI3Kα ( IC50: 104 nM in H358 cells). VVD-699 inhibits phosphorylated AKT. VVD-699 can be used for the research of KRAS mutant/amplified cancer [1].
In Vivo, Combination treatment with VVD-699 (30 mg/kg; p.o.; twice daily) and Sotorasib yields greater benefits than the combination of Sotorasib and Binimetinib in the H2122 xenograft mouse model, and triple combination of the three agents induces durable tumor regression[1].
In Vitro, VVD-699 (0.002-5 μM; 2 h) inhibits phosphorylated AKT in KRASGly12Ser A549 human lung cancer cells[1].
References:
[1]. Klebba JE, et al. Covalent inhibitors of the RAS binding domain of PI3Kα impair tumor growth driven by RAS and HER2. bioRxiv [Preprint]. 2024 Dec 20:2024.12.17.629001. doi: 10.1101/2024.12.17.629001. Update in: Science. 2025 Nov 13;390(6774):702-709.
In Vivo, Combination treatment with VVD-699 (30 mg/kg; p.o.; twice daily) and Sotorasib yields greater benefits than the combination of Sotorasib and Binimetinib in the H2122 xenograft mouse model, and triple combination of the three agents induces durable tumor regression[1].
In Vitro, VVD-699 (0.002-5 μM; 2 h) inhibits phosphorylated AKT in KRASGly12Ser A549 human lung cancer cells[1].
References:
[1]. Klebba JE, et al. Covalent inhibitors of the RAS binding domain of PI3Kα impair tumor growth driven by RAS and HER2. bioRxiv [Preprint]. 2024 Dec 20:2024.12.17.629001. doi: 10.1101/2024.12.17.629001. Update in: Science. 2025 Nov 13;390(6774):702-709.