Sotorasib
(Synonyms: 索托拉西布; AMG-510) 目录号 : GC62238
Sotorasib（AMG510）是一种有效的KRASG12C（KRAS蛋白12位的甘氨酸突变为半胱氨酸）共价抑制剂，通过将KRASG12C锁定在无活性的GDP结合状态，特异性且不可逆地抑制KRASG12C。Sotorasib是一种手性化合物，具有潜在的抗肿瘤活性。
Cas No.:2296729-00-3
Sample solution is provided at 25 µL, 10mM.
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Sotorasib (AMG510) is a potent covalent inhibitor of KRASG12C (Glycine at position 12 of KRAS protein mutated to cysteine) that specifically and irreversibly inhibits KRASG12C by locking KRASG12C in an inactive GDP-bound state. Sotorasib is a chiral compound with potential anti-tumor activity [1].
In NCI-H358 and MIA PaCa-2 cells, Sotorasib almost completely inhibited p-ERK (IC50 is 0.03μM) levels and significantly inhibited cell viability, with IC50 values of 0.006μM and 0.009μM respectively [2]. Using different concentrations of Sotorasib to treat KRAS mutant cell line H23 (1μM), wild-type KRAS cell line H522 (15μM) and A549 cells (25μM) can inhibit cell viability and induce cell apoptosis [3].
In the KRASG12C tumor model, Sotorasib (30-100mg/kg) inhibited p-ERK in a dose-dependent manner 2 hours after treatment. In mice xenografted with human tumor cells, Sotorasib (3, 10, 30 and 100mg/kg) significantly inhibited the growth of MIA PaCa-2 T2 and NCI-H358 tumors at all doses and at 100mg/kg Tumor regression was observed at the dose [2]. Sotorasib (25mg/kg) significantly reduced the volume, weight, and size of mouse tumors in the MIA PaCa-2 tumor xenograft model without any evidence of organ toxicity or metastatic spread[4].
References:
[1] Fakih M, O'Neil B, Price T J, et al. Phase 1 study evaluating the safety, tolerability, pharmacokinetics (PK), and efficacy of AMG 510, a novel small molecule KRASG12C inhibitor, in advanced solid tumors[J]. 2019.
[2] Canon J, Rex K, Saiki A Y, et al. The clinical KRAS (G12C) inhibitor AMG 510 drives anti-tumour immunity[J]. Nature, 2019, 575(7781): 217-223.
[3] Barrios-Bernal P, Lucio-Lozada J, Ramos-Ramírez M, et al. A Novel Combination of Sotorasib and Metformin Enhances Cytotoxicity and Apoptosis in KRAS-Mutated Non-Small Cell Lung Cancer Cell Lines through MAPK and P70S6K Inhibition[J]. International Journal of Molecular Sciences, 2023, 24(5): 4331.
[4] Khan H Y, Nagasaka M, Aboukameel A, et al. Anticancer Efficacy of KRASG12C Inhibitors Is Potentiated by PAK4 Inhibitor KPT9274 in Preclinical Models of KRAS G12C-Mutant Pancreatic and Lung Cancers[J]. Molecular Cancer Therapeutics, 2023, 22(12): 1422-1433.
Sotorasib（AMG510）是一种有效的KRASG12C（KRAS蛋白12位的甘氨酸突变为半胱氨酸）共价抑制剂，通过将KRASG12C锁定在无活性的GDP结合状态，特异性且不可逆地抑制KRASG12C。Sotorasib是一种手性化合物，具有潜在的抗肿瘤活性[1]。
在NCI-H358和MIA PaCa-2细胞中，Sotorasib几乎完全抑制了p-ERK（IC50为0.03μM）水平，并且显著抑制细胞活力，IC50值分别为0.006μM和0.009μM[2]。使用不同浓度的Sotorasib处理KRAS突变细胞系H23（1μM）、野生型KRAS细胞系H522（15μM）和A549细胞（25μM），可抑制细胞活力，诱导细胞凋亡[3]。
在KRASG12C肿瘤模型中，Sotorasib（30-100mg/kg）在治疗后2小时以剂量依赖性方式抑制p-ERK。在人类肿瘤细胞异种移植的小鼠中，Sotorasib（3、10、30和100mg/kg）在所有剂量下均能显著抑制MIA PaCa-2 T2和NCI-H358肿瘤的生长，并且在100mg/kg剂量下观察到肿瘤的消退[2]。Sotorasib（25mg/kg）可明显减小MIA PaCa-2肿瘤异种移植模型中小鼠肿瘤的体积、重量和大小，并且未发现任何器官毒性或转移扩散迹象[4]。
| Cell experiment [1]: | |
Cell lines | Sotorasib-resistant parental cell line (MIA PaCa-R) and Sotorasib-sensitive parental cell line (MIA PaCa-2) |
Preparation Method | Cell viability was assayed by MTT assay after incubating different concentrations of Sotorasib with cells for 72 h. |
Reaction Conditions | 0-1.6μM, 72 h |
Applications | Sotorasib inhibited MIA PaCa-R and MIA PaCa-2 cell viability with IC50 of 2.789μM and 66.17nM, respectively. |
| Animal experiment [1]: | |
Animal models | MIA PaCa-2 cell-derived tumor xenograft model |
Preparation Method | Hormonal mice were randomized into 4 groups of 6 mice each to receive either vector or or KPT9274 (100mg/kg every day × 5×3 weeks), or Sotorasib (25mg/kg every day × 5×3 weeks), or their combination by oral gavage. |
Dosage form | 25mg/kg, Five times a week for three weeks, i.g. |
Applications | Sotorasib significantly reduced tumor volume, tumor weight and tumor size. |
References: [1] Khan H Y, Nagasaka M, Aboukameel A, et al. Anticancer Efficacy of KRASG12C Inhibitors Is Potentiated by PAK4 Inhibitor KPT9274 in Preclinical Models of KRAS G12C-Mutant Pancreatic and Lung Cancers[J]. Molecular Cancer Therapeutics, 2023, 22(12): 1422-1433. | |
| Cas No. | 2296729-00-3 | SDF | |
| 别名 | 索托拉西布; AMG-510 | ||
| 分子式 | C30H30F2N6O3 | 分子量 | 560.59 |
| 溶解度 | DMSO : 50 mg/mL (89.19 mM; Need ultrasonic)；Water : 33.33 mg/mL (59.46 mM; ultrasonic and adjust pH to 11 with NaOH) | 储存条件 | Store at -20°C,protect from light, stored under nitrogen |
| General tips | 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 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.7838 mL | 8.9192 mL | 17.8383 mL |
| 5 mM | 0.3568 mL | 1.7838 mL | 3.5677 mL |
| 10 mM | 0.1784 mL | 0.8919 mL | 1.7838 mL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
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