Adagrasib(Synonyms: MRTX849)

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Adagrasib (Synonyms: MRTX849) 纯度: 99.85%

Adagrasib (MRTX849) 是一种有效，口服可用，突变选择性的 KRAS G12C 共价抑制剂，具有潜在抗肿瘤活性的。Adagrasib 在半胱氨酸 12 残基处与 KRAS G12C 共价结合，将蛋白锁定在非活性的 GDP 结合构象中，并抑制 KRAS 依赖性信号转导。

Adagrasib(Synonyms: MRTX849)

Adagrasib Chemical Structure

CAS No. : 2326521-71-3

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10 mM * 1 mL in DMSO ￥1270 In-stock
10 mg ￥1150 In-stock
25 mg ￥2500 In-stock
50 mg ￥4500 In-stock
100 mg ￥6800 In-stock
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500 mg   询价  

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生物活性

Adagrasib (MRTX849) is a potent, orally-available, and mutation-selective covalent inhibitor of KRAS G12C with potential antineoplastic activity. Adagrasib covalently binds to KRAS G12C at the cysteine at residue 12, locks the protein in its inactive GDP-bound conformation, and inhibits KRAS-dependent signal transduction[1][2].

IC50 & Target

KRas G12C

 

体外研究
(In Vitro)

MRTX849 (0.1-10000 nM; 3 天 /2D 条件，12 天 /3D 条件) 对绝大多数 KRAS G12C 突变体细胞系的生长有明显的抑制作用，其 IC50 在 2D 条件下为 10~973 nM，3D 条件为 0.2~1042 nM[1]。
MRTX849 (0.24-1000nM; 24 小时) 抑制 KRAS 依赖的信号转导靶点，包括 ERK1/2 磷酸化 (Thr202/Tyr204 ERK1; pERK)、S6 磷酸化

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Viability Assay[1]

Cell Line: MIA PaCa-2, H1373, H358, H2122, SW1573, H2030, KYSE-410 cells (G12C); H1299 (WT); A549 (G12S), HCT116 (G13D) cells
Concentration: 0.1, 1, 10, 100, 1000, 10000 nM
Incubation Time: 24 hours
Result: Inhibits cell growth in the vast majority of KRAS G12C-mutant cell lines with IC50 values ranging between 10 and 973 nM in the 2D format and between 0.2 and 1042 nM in the 3D format.

Western Blot Analysis[1]

Cell Line: MIA PaCa-2 cells
Concentration: 0.24, 0.5, 1.0, 2.0, 3.9, 7.8, 15.6, 31.3, 62.5, 125, 250, 500, 1000 nM
Incubation Time: 24 hours
Result: Inhibits KRAS-dependent signaling targets including ERK1/2 phosphorylation (Thr202/Tyr204 ERK1; pERK), S6 phosphorylation (RSK-dependent Ser235/236; pS6) and expression of the ERK-regulated DUSP6, each with IC50s in the single-digit nanomolar range in cell lines.

体内研究
(In Vivo)

MRTX849 (1-100 mg/kg；口腔灌胃.；每日一次至第 16 天) 在耐受良好的剂量范围内显示剂量依赖性抗肿瘤疗效，MRTX849 的最大有效剂量在 30-100 mg/kg/天之间[1]。

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: MIA PaCa-2 model (6-8-week-old, female, athymic nude-Foxn1 nu mice)[1]
Dosage: 1, 3, 10, 30 and 100 mg/kg
Administration: Oral gavage; daily until Day 16
Result: Rapid tumor regression was observed at the earliest posttreatment tumor measurement and animals in the 30 and 100 mg/kg cohorts exhibited evidence of a complete response at study Day 15. Dosing was stopped at study Day 16 and all 4 mice in the 100 mg/kg cohort and 2 out of 7 mice in the 30 mg/kg cohort remained tumor-free through study Day 70.

Clinical Trial

分子量

604.12

Formula

C32H35ClFN7O2
CAS 号

2326521-71-3
运输条件

Room temperature in continental US; may vary elsewhere.
储存方式

-20°C, stored under nitrogen

*In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
溶解性数据
In Vitro: 

DMSO : 100 mg/mL (165.53 mM; Need ultrasonic)

配制储备液
浓度 溶剂体积 质量 1 mg 5 mg 10 mg
1 mM 1.6553 mL 8.2765 mL 16.5530 mL
5 mM 0.3311 mL 1.6553 mL 3.3106 mL
10 mM 0.1655 mL 0.8277 mL 1.6553 mL

*

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month (stored under nitrogen)。-80°C 储存时，请在 6 个月内使用，-20°C 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： 5% DMSO    40% PEG300    5% Tween-80    50% saline

    Solubility: ≥ 2.62 mg/mL (4.34 mM); Clear solution

  • 2.

    请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

    Solubility: ≥ 2.5 mg/mL (4.14 mM); Clear solution

    此方案可获得 ≥ 2.5 mg/mL (4.14 mM，饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例，取 100 μL 25.0 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。

    将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

  • 3.

    请依序添加每种溶剂： 10% DMSO    90% corn oil

    Solubility: ≥ 2.5 mg/mL (4.14 mM); Clear solution

    此方案可获得 ≥ 2.5 mg/mL (4.14 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 25.0 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 上海金畔生物科技有限公司 网站选购。
参考文献

  • [1]. Christensen JG, et al. The KRASG12C Inhibitor, MRTX849, Provides Insight Toward Therapeutic Susceptibility of KRAS Mutant Cancers in Mouse Models and Patients. Cancer Discov. 2019 Oct 28. pii: CD-19-1167.

    [2]. Kyriakos P. Papadopoulos, et al. A phase I/II multiple expansion cohort trial of MRTX849 in patients with advanced solid tumors with KRAS G12C mutation. Journal of Clinical Oncology 2019 37:15_suppl, TPS3161-TPS3161.

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