Opnurasib (JDQ-443) (NVP-JDQ443) 是一种口服有效和选择性的共价KRAS G12C抑制剂。Opnurasib 具有抗肿瘤活性。
| 生物活性 | Opnurasib (JDQ-443) (NVP-JDQ443) is an orally active, potent, selective, and covalentKRAS G12Cinhibitor (extracted from patent WO2021120890A1). Opnurasib shows antitumor activity[1][2]. |
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体外研究
(In Vitro) | Opnurasib (NVP-JDQ443) traps the GDP-bound inactive conformation of KRAS[1].
Opnurasib promotes dose-dependent reductions of phosphorylated ERK (pERK) levels and the proliferation of the KRASG12C-mutated cell lines NCI-H358 and NCI-H2122, with IC50values of 0.018 and 0.063 μM, respectively[2].
Opnurasib covalently and selectively binds and inhibits GDP-bound KRASG12C with low reversible binding affinity to the RAS switch II pocket, and also inhibits proliferation of KRASG12C-mutated and KRAS G12C/H95, G12C/R68S, and G12C/Y96 double-mutant cell lines[2].
Western Blot Analysis | Cell Line: | Ba/F3 cells[2] | | Concentration: | 0, 0.3, 1 μM | | Incubation Time: | 30 min, 4 h | | Result: | Inhibited signaling (pERK) and proliferation of the KRAS G12C/H95 double mutants G12C/H95R and G12C/H95Q. |
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体内研究
(In Vivo) | Opnurasib (10-100 mg/kg, Orally, daily for 14 days) shows antitumor activity in KRAS G12C-mutated CDX models[2].
Opnurasib (Orally, 100 mg/kg, daily (JDQ443) + 7.5 mg/kg, twice daily (TNO155), for 36 days) shows greater cell growth inhibition or cell killing compared with single-agent JDQ443 when combined with TNO155[2].
Opnurasib generates categorical antitumor responses in PDX models of NSCLC and colorectal tumors that are improved by combination treatment with other agents[2].
| Animal Model: | KRAS G12C tumor-bearing nude mice (MIA PaCa-2 (PDAC); NCIH2122, LU99, HCC44, NCI-H2030 (NSCLC); and KYSE410 (esophageal cancer))[2] | | Dosage: | 10, 30, 100 mg/kg | | Administration: | Orally, daily for 14 days | | Result: | Inhibited the growth of all models in a dose-dependent manner. |
| Animal Model: | Three KRAS G12C-mutated CDX models (LU99, NCI-H2030, and KYSE410)[2] | | Dosage: | 100 mg/kg (JDQ443) + 7.5 mg/kg (TNO155) | | Administration: | Orally, daily (JDQ443) or twice daily (TNO155), for 36 days | | Result: | Combined with TNO155, showed either greater tumor efficacy compared with each agent alone (H2030, KYSE410) or a delayed time to tumor progression (LU99). |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : 80 mg/mL(152.08 mM;Need ultrasonic) 配制储备液 | 1 mM | 1.9010 mL | 9.5052 mL | 19.0103 mL | | 5 mM | 0.3802 mL | 1.9010 mL | 3.8021 mL | | 10 mM | 0.1901 mL | 0.9505 mL | 1.9010 mL |
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储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂： ——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；
以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂： 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2.08 mg/mL (3.95 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (3.95 mM，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；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。 2. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 2.08 mg/mL (3.95 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (3.95 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。 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。 *以上所有助溶剂都可在本网站选购。
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