ARS-1620

KRAS^G12C, a mutant of KRAS at codon 12, was recently identified to be potentially druggable by allele-specific covalent targeting of Cys-12 in vicinity to an inducible allosteric switch II pocket (S-IIP)². ARS-1620 is an atropisomeric potent and selective KRAS^G12C inhibitor with desirable PK. Across a panel of cell lines (n = 4) harboring the mutant allele, ARS-1620 rapidly engaged G12C in a concentration- and time- dependent manner. After 2 hr of treatment, ARS-1620 exhibited a half maximal G12C target engagement (TE₅₀) at ∼0.3 μM and near complete engagement at 3.0 μM. Following a 5-day treatment period aimed to assess the effect on inhibiting cell growth, ARS-1620 exhibited complete growth suppression of p.G12C cell lines (150 nM IC₅₀) with relatively benign effects on control cell lines. ARS-1620 induced significant (tumor growth inhibition) TGI (p < 0.001) and marked regression in p.G12C PDX models following 3 weeks of treatment using a daily 200 mg/kg schedule².

溶解方案(细胞实验)

DMSO 中的溶解度 : 125 mg/mL (290.13 mM; 超声助溶; 吸湿的 DMSO 对产品的溶解度有显著影响，请使用新开封的 DMSO)|H₂O 中的溶解度 : 11 mg/mL (25.53 mM; 超声助溶; 酸性条件溶解 (HCl 调节，pH≈3))

溶解方案(动物实验)

"方案 一": "请依序添加每种溶剂：10% DMSO 40% PEG300 5% Tween-80 45% SalineSolubility: ≥ 2.08 mg/mL (4.83 mM); 澄清溶液 此方案可获得 ≥ 2.08 mg/mL（饱和度未知）的澄清溶液。以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；再向上述体系中加入 50 μL Tween-80，混合均匀；然后再继续加入 450 μL 生理盐水 定容至 1 mL。生理盐水的配制：将 0.9 g 氯化钠，溶解于 ddH₂O 并定容至 100 mL，可以得到澄清透明的生理盐水溶液。"

"方案 二": "请依序添加每种溶剂：10% DMSO 90% (20% SBE-β-CD in Saline)Solubility: ≥ 2.08 mg/mL (4.83 mM); 澄清溶液 此方案可获得 ≥ 2.08 mg/mL（饱和度未知）的澄清溶液。以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液 中，混合均匀。2 g SBE-β-CD（磺丁基醚 β-环糊精）粉末定容于 10 mL 的生理盐水中，完全溶解至澄清透明。"

"方案 三": "请依序添加每种溶剂：10% DMSO 90% Corn OilSolubility: ≥ 2.08 mg/mL (4.83 mM); 澄清溶液 此方案可获得 ≥ 2.08 mg/mL（饱和度未知）的澄清溶液，此方案实验周期在半个月以上的动物实验酌情使用。以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。"