| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Mutant KRAS G12C (irreversibly binds to the switch II pocket, Ki = 11 nM for KRAS G12C-GDP; IC50 = 0.21 μM for inhibiting KRAS G12C-mediated signaling in H358 cells) [6]
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|---|---|
| ln Vitro |
- Sotorasib (AMG-510) potently inhibited proliferation of KRAS G12C-positive cancer cell lines, with IC50 values of 0.01-0.5 μM (e.g., H358 lung adenocarcinoma: 0.03 μM; MIA PaCa-2 pancreatic cancer: 0.12 μM) as measured by CellTiter-Glo assay. It had no significant effect on KRAS wild-type or non-G12C mutant cells (IC50 > 10 μM) [6]
- In H358 cells, sotorasib (0.1-1 μM) dose-dependently reduced phosphorylation of KRAS downstream effectors (p-ERK, p-AKT, p-S6) within 2 hours (Western blot), with maximal inhibition at 1 μM [6] - The compound (1 μM) induced apoptosis in KRAS G12C-positive cells (Annexin V/PI staining) and reduced colony formation (by 80% in H358 cells) compared to vehicle [6] |
| ln Vivo |
- In mice bearing H358 xenografts (KRAS G12C), sotorasib (10-180 mg/kg, oral gavage, daily for 21 days) caused dose-dependent tumor regression: 180 mg/kg led to 90% tumor growth inhibition (TGI) and 30% complete regression. No significant effect was observed in KRAS wild-type A549 xenografts [6]
- In a patient-derived xenograft (PDX) model of KRAS G12C colorectal cancer, sotorasib (100 mg/kg, oral) reduced tumor volume by 65% after 28 days, with decreased p-ERK levels in tumor tissues (immunohistochemistry) [3] |
| Enzyme Assay |
- KRAS G12C binding assay: Purified KRAS G12C-GDP protein was incubated with sotorasib (0.1-100 nM) and analyzed by surface plasmon resonance (SPR). The compound showed slow dissociation (t1/2 = 10 hours) with a Ki of 11 nM. GTPase activity was measured using a luminescent GTP hydrolysis assay, where sotorasib (1 μM) inhibited KRAS G12C GTPase activity by 85% [6]
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| Cell Assay |
- Proliferation assay: KRAS G12C-positive cells (H358, MIA PaCa-2) were seeded in 96-well plates and treated with sotorasib (0.001-10 μM) for 72 hours. Cell viability was assessed using CellTiter-Glo, and IC50 was calculated via nonlinear regression [6]
- Western blot for signaling: H358 cells were serum-starved, treated with sotorasib (0.1-1 μM) for 2 hours, then lysed. Lysates were probed with antibodies against p-ERK, p-AKT, and total ERK/AKT. Band intensities were normalized to β-actin [6] |
| Animal Protocol |
- Xenograft model: Nude mice were subcutaneously injected with H358 cells (5×10⁶). When tumors reached 100-200 mm³, sotorasib (10-180 mg/kg) was administered by oral gavage once daily. Tumor volume (calipers) and body weight were measured twice weekly for 21 days. Tumor tissues were harvested for immunohistochemical analysis of p-ERK [6]
- PDX model: Mice bearing KRAS G12C colorectal cancer PDXs received sotorasib (100 mg/kg, oral) daily for 28 days. Tumor growth was monitored, and Ki-67 (proliferation marker) expression was quantified [3] |
| ADME/Pharmacokinetics |
- In mice, oral administration of sotorasibel (10 mg/kg) resulted in a bioavailability of 70%, with a peak plasma concentration (Cmax) of 2.3 μg/mL at 1 hour. Its plasma half-life (t1/2) was 4.5 hours, and it exhibited good tumor penetration (tumor/plasma ratio of 3.2) [6]
- In patients, oral administration of sotorasibel (960 mg) resulted in a Cmax of 7.1 μg/mL at 1.5 hours, with a terminal half-life of 5 hours. Plasma protein binding was 95% [4] |
| Toxicity/Toxicokinetics |
In preclinical studies, sotorasirb (orally, at doses up to 300 mg/kg) showed no significant toxicity in mice, with normal liver and kidney function [6]. In clinical trials, common adverse events (≥15%) included diarrhea (34%), nausea (25%), and fatigue (21%). Grade 3/4 toxicities were rare (<5%), and no dose-limiting nephrotoxicity or hepatotoxicity was observed [4].
|
| References | |
| Additional Infomation |
Sotorasib (AMG-510) is a first-in-class covalent inhibitor that irreversibly binds to the GDP-binding form of KRAS G12C, rendering it inactive [6] - it is indicated for the treatment of KRAS G12C-mutant non-small cell lung cancer (NSCLC) that has previously received systemic therapy and was approved by the FDA in 2021 [3][4]
|
| Molecular Formula |
C30H30F2N6O3
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|---|---|
| Molecular Weight |
560.6
|
| Exact Mass |
560.23
|
| Elemental Analysis |
C, 64.28; H, 5.39; F, 6.78; N, 14.99; O, 8.56
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| Related CAS # |
Sotorasib;2296729-00-3;Sotorasib racemate;2252403-56-6
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| PubChem CID |
137278711
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| Appearance |
Typically exists as solid at room temperature
|
| LogP |
4
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
5
|
| Heavy Atom Count |
41
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| Complexity |
1030
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| Defined Atom Stereocenter Count |
1
|
| SMILES |
C[C@H]1CN(CCN1C2=NC(=O)N(C3=NC(=C(C=C32)F)C4=C(C=CC=C4F)O)C5=C(C=CN=C5C(C)C)C)C(=O)C=C
|
| InChi Key |
NXQKSXLFSAEQCZ-SFHVURJKSA-N
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| InChi Code |
InChI=1S/C30H30F2N6O3/c1-6-23(40)36-12-13-37(18(5)15-36)28-19-14-21(32)26(24-20(31)8-7-9-22(24)39)34-29(19)38(30(41)35-28)27-17(4)10-11-33-25(27)16(2)3/h6-11,14,16,18,39H,1,12-13,15H2,2-5H3/t18-/m0/s1
|
| Chemical Name |
6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(4-methyl-2-propan-2-ylpyridin-3-yl)-4-[(2S)-2-methyl-4-prop-2-enoylpiperazin-1-yl]pyrido[2,3-d]pyrimidin-2-one
|
| Synonyms |
Sotorasib; AMG-510; 2296729-00-3; ...; Kras mutant-targeting AMG 510; ...; Sotorasib isomer;
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
H2O :< 0.1 mg/mL
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (2.23 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7838 mL | 8.9190 mL | 17.8380 mL | |
| 5 mM | 0.3568 mL | 1.7838 mL | 3.5676 mL | |
| 10 mM | 0.1784 mL | 0.8919 mL | 1.7838 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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