BI-3406

선택적 SOS1 억제제인 BI-3406은 MIA PaCa-2 세포에서 AMG 510 유도 성장 억제를 강화했습니다. 내인성 돌연변이 KRAS의 절제 후 이 화합물 5 µM로 처리하면 ERK 및 AKT 활성화가 모두 소멸되며, 이는 WT RAS 신호 억제와 일치합니다.[1]

강력하고 선택적인 SOS1-KRAS 상호작용 억제제인 BI-3406은 MEK 억제와 결합하여 KRAS-유도 암에 효과적입니다.[2]

• 세포주

  MIA PaCa-2, mT42 cells

• 농도

  5 μM, 20 μM to 2 nM

• 배양 시간

  4 days

• 방법

  MIA PaCa-2 cells were seeded at 2,000 cells per well and treated 24 h after seeding with 5 μM BI-3406 or DMSO control and AMG 510 (from 5 μM to 0.1 nM). Cell viability was measured after 4 d with CellTiter-Glo. mT42 cells were seeded at 1,000 cells per well and treated with 4-OHT or DMSO control and this compound in a dose–response manner (from 20 μM to 2 nM). Cell viability was measured using CellTiter-Glo Luminescence assay at day 4. FPC cell line mT42 cells were treated with 5 μM this compound, or DMSO vehicle control in the presence or absence of mutant KRAS by treatment with DMSO vehicle control or 4-OHT, respectively. Immunoblotting was performed for RAS pathways by phospho-ERK and phospho-AKT and the RSK1 substrate phospho-S6.

• 동물 모델

  NSG female mice of KRAS G12V and KRAS Q61K mutant pancreatic PDX model

• 용량

  50 mg/kg

• 투여

  p.o.