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Reagents and instruments for immunology, cell biology and molecular biology.

Sotorasib [2296729-00-3]

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Cat# HY-114277-10mg

Size : 10mg

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Phone : +1 850 650 7790

Brand : MedChemExpress

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Description

Sotorasib (AMG-510) is a first-in-class, orally bioavailable, and selective KRAS G12C covalent inhibitor. Sotorasib irreversibly inhibits KRAS G12C by locking it in an inactive GDP-bound state. Sotorasib leads to the regression of KRAS G12C‑mutated locally advanced or metastatic non‑small cell lung cancer (NSCLC)^[1]^[2]^[3]^[4]^[5]^[6].

IC₅₀ & Target^[1]

KRAS(G12C)

Cellular Effect

Cell Line	Type	Value	Description	References
A549	IC₅₀	> 10 μM Compound: 2; AMG510	Antiproliferative activity against human A549 cells harboring KRAS G12S mutant assessed as growth inhibition measured after 72 hrs by SRB assay Antiproliferative activity against human A549 cells harboring KRAS G12S mutant assessed as growth inhibition measured after 72 hrs by SRB assay	[PMID: 33309163]
A549	IC₅₀	36.5 μM Compound: (R)-38; AMG-510	Antiproliferative activity against human A549 cells harboring KRAS G12S point mutant assessed as cell growth inhibition after 72 hrs by Celltiter-Glo luminescent cell viability assay Antiproliferative activity against human A549 cells harboring KRAS G12S point mutant assessed as cell growth inhibition after 72 hrs by Celltiter-Glo luminescent cell viability assay	[PMID: 31820981]
A549	IC₅₀	50 μM Compound: 2; AMG510	Antiproliferative activity against human A549 cells harboring KRAS G12S mutant measured after 72 hrs by CCK-8 assay Antiproliferative activity against human A549 cells harboring KRAS G12S mutant measured after 72 hrs by CCK-8 assay	[PMID: 35007863]
MIA PaCa-2	IC₅₀	0.005 μM Compound: (R)-38; AMG-510	Antiproliferative activity against human MIAPaCa2 cells harboring KRAS G12C point mutant assessed as cell growth inhibition after 72 hrs by Celltiter-Glo luminescent cell viability assay Antiproliferative activity against human MIAPaCa2 cells harboring KRAS G12C point mutant assessed as cell growth inhibition after 72 hrs by Celltiter-Glo luminescent cell viability assay	[PMID: 31820981]
MIA PaCa-2	IC₅₀	0.029 μM Compound: 2; AMG510	Antiproliferative activity against human MIA PaCa-2 cells harboring KRAS G12C mutant assessed as growth inhibition measured after 72 hrs by CCK8 assay Antiproliferative activity against human MIA PaCa-2 cells harboring KRAS G12C mutant assessed as growth inhibition measured after 72 hrs by CCK8 assay	[PMID: 33309163]
NCI-H1373	IC₅₀	> 10000 nM Compound: AMG-510	Cytotoxicity against human NCI-H1373 cells harboring KRAS G12C mutant assessed as reduction in cell viability measured after 72 hrs by CellTiter-Glo luciferase-based ATP detection assay Cytotoxicity against human NCI-H1373 cells harboring KRAS G12C mutant assessed as reduction in cell viability measured after 72 hrs by CellTiter-Glo luciferase-based ATP detection assay	[PMID: 34676026]
NCI-H1373	IC₅₀	355.7 nM Compound: AMG-510	Cytotoxicity against human NCI-H1373 cells harboring KRASG12C mutant assessed as reduction in cell viability measured after 72 hrs in presence of compound 1 by CellTiter-Glo luciferase-based ATP detection assay Cytotoxicity against human NCI-H1373 cells harboring KRASG12C mutant assessed as reduction in cell viability measured after 72 hrs in presence of compound 1 by CellTiter-Glo luciferase-based ATP detection assay	[PMID: 34676026]
NCI-H1792	IC₅₀	> 10000 nM Compound: AMG-510	Cytotoxicity against human NCI-H1792 cells harboring KRAS G12C mutant assessed as reduction in cell viability measured after 72 hrs by CellTiter-Glo luciferase-based ATP detection assay Cytotoxicity against human NCI-H1792 cells harboring KRAS G12C mutant assessed as reduction in cell viability measured after 72 hrs by CellTiter-Glo luciferase-based ATP detection assay	[PMID: 34676026]
NCI-H1792	IC₅₀	3000 nM Compound: AMG-510	Cytotoxicity against human NCI-H1792 cells harboring KRASG12C mutant assessed as reduction in cell viability measured after 72 hrs in presence of compound 1 by CellTiter-Glo luciferase-based ATP detection assay Cytotoxicity against human NCI-H1792 cells harboring KRASG12C mutant assessed as reduction in cell viability measured after 72 hrs in presence of compound 1 by CellTiter-Glo luciferase-based ATP detection assay	[PMID: 34676026]
NCI-H1975	IC₅₀	> 10 μM Compound: 2; AMG510	Antiproliferative activity against human NCI-H1975 cells harboring wild-type KRAS assessed as growth inhibition measured after 72 hrs by SRB assay Antiproliferative activity against human NCI-H1975 cells harboring wild-type KRAS assessed as growth inhibition measured after 72 hrs by SRB assay	[PMID: 33309163]
NCI-H2122	IC₅₀	530.3 nM Compound: AMG-510	Cytotoxicity against human NCI-H2122 cells harboring KRAS G12C mutant assessed as reduction in cell viability measured after 72 hrs by CellTiter-Glo luciferase-based ATP detection assay Cytotoxicity against human NCI-H2122 cells harboring KRAS G12C mutant assessed as reduction in cell viability measured after 72 hrs by CellTiter-Glo luciferase-based ATP detection assay	[PMID: 34676026]
NCI-H2122	IC₅₀	90.5 nM Compound: AMG-510	Cytotoxicity against human NCI-H2122 cells harboring KRASG12C mutant assessed as reduction in cell viability measured after 72 hrs in presence of compound 1 by CellTiter-Glo luciferase-based ATP detection assay Cytotoxicity against human NCI-H2122 cells harboring KRASG12C mutant assessed as reduction in cell viability measured after 72 hrs in presence of compound 1 by CellTiter-Glo luciferase-based ATP detection assay	[PMID: 34676026]
NCI-H23	IC₅₀	> 10000 nM Compound: AMG-510	Cytotoxicity against human NCI-H23 cells harboring KRAS G12C mutant assessed as reduction in cell viability measured after 72 hrs by CellTiter-Glo luciferase-based ATP detection assay Cytotoxicity against human NCI-H23 cells harboring KRAS G12C mutant assessed as reduction in cell viability measured after 72 hrs by CellTiter-Glo luciferase-based ATP detection assay	[PMID: 34676026]
NCI-H23	IC₅₀	111.5 nM Compound: 2; AMG510	Antiproliferative activity against human NCI-H23 cells harboring KRAS G12C mutant measured after 72 hrs by CCK-8 assay Antiproliferative activity against human NCI-H23 cells harboring KRAS G12C mutant measured after 72 hrs by CCK-8 assay	[PMID: 35007863]
NCI-H23	IC₅₀	1500 nM Compound: AMG-510	Cytotoxicity against human NCI-H23 cells harboring KRASG12C mutant assessed as reduction in cell viability measured after 72 hrs in presence of compound 1 by CellTiter-Glo luciferase-based ATP detection assay Cytotoxicity against human NCI-H23 cells harboring KRASG12C mutant assessed as reduction in cell viability measured after 72 hrs in presence of compound 1 by CellTiter-Glo luciferase-based ATP detection assay	[PMID: 34676026]
NCI-H358	IC₅₀	< 0.016 μM Compound: 2; AMG510	Antiproliferative activity against human NCI-H358 cells harboring KRAS G12C mutant assessed as growth inhibition measured after 72 hrs by SRB assay Antiproliferative activity against human NCI-H358 cells harboring KRAS G12C mutant assessed as growth inhibition measured after 72 hrs by SRB assay	[PMID: 33309163]
NCI-H358	IC₅₀	213 nM Compound: AMG-510	Cytotoxicity against human NCI-H358 cells harboring KRAS G12C mutant assessed as reduction in cell viability measured after 72 hrs by CellTiter-Glo luciferase-based ATP detection assay Cytotoxicity against human NCI-H358 cells harboring KRAS G12C mutant assessed as reduction in cell viability measured after 72 hrs by CellTiter-Glo luciferase-based ATP detection assay	[PMID: 34676026]
NCI-H358	IC₅₀	3 nM Compound: AMG-510	Cytotoxicity against human NCI-H358 cells harboring KRASG12C mutant assessed as reduction in cell viability measured after 72 hrs in presence of compound 1 by CellTiter-Glo luciferase-based ATP detection assay Cytotoxicity against human NCI-H358 cells harboring KRASG12C mutant assessed as reduction in cell viability measured after 72 hrs in presence of compound 1 by CellTiter-Glo luciferase-based ATP detection assay	[PMID: 34676026]
NCI-H358	EC₅₀	6.4 nM Compound: AMG-510	Antiproliferative activity against human NCI-H358 cells harboring KRAS G12C mutant incubated for 3 days by celltiter glo luminescent assay Antiproliferative activity against human NCI-H358 cells harboring KRAS G12C mutant incubated for 3 days by celltiter glo luminescent assay	[PMID: 36300829]
NCI-H358	IC₅₀	8.4 nM Compound: 2; AMG510	Antiproliferative activity against human NCI-H358 cells harboring KRAS G12C mutant measured after 72 hrs by CCK-8 assay Antiproliferative activity against human NCI-H358 cells harboring KRAS G12C mutant measured after 72 hrs by CCK-8 assay	[PMID: 35007863]

In Vitro

In cellular assays, Sotorasib (AMG-510) covalently modifies KRAS G12C and inhibits KRAS G12C signaling as measured by phosphorylation of ERK1/2 (p-ERK) in all KRAS p.G12C-mutant cell lines^[2].
Sotorasib (AMG-510; 1-10 μM; 72 hours) also potently impairs cellular viability in both NCI-H358 and MIA PaCa-2 with IC₅₀≈0.006 μM and 0.009 μM, respectively. Non-KRASG12C lines are insensitive to Sotorasib (IC₅₀>7.5 μM)^[3].
Sotorasib (AMG-510) (0-50 μM, 72 h) inhibits cell growth and has a synergistic effect with Cisplatin (HY-17394) in H23 and H358 cells^[5].
Sotorasib (AMG-510) (100 nM, 4-72 h) has sustained suppression against active KRAS, but still observes adaptive feedback reactivation of RAS-MAPK^[6].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Viability Assay^[3]

Cell Line:	NCI-H358 and MIA PaCa-2 cells
Concentration:	1-10 μM
Incubation Time:	72 hours
Result:	Potently impaired cellular viability in both NCI-H358 and MIA PaCa-2 (IC₅₀=~0.006 μM and ~0.009 μM respectively).

Cell Viability Assay^[5]

Cell Line:	NCI-H23 (H23) and NCI-H358 (H358) cells (Lung adenocarcinoma cell lines harbor KRAS G12C mutations)
Concentration:	0-50 μM
Incubation Time:	72 h
Result:	The IC₅₀ values in H358 and H23 cell lines were 0.0818 μM, 0.6904 μM, respectively. Had a synergistic effect with Cisplatin (HY-17394).

Western Blot Analysis^[6]

Cell Line:	H358, MGH1088-1, MGH1062, MIA PaCa-2, B8182, LIM2099, SW837, SW1463 (KRAS-^G12C mutant cell lines)
Concentration:	100 nM
Incubation Time:	4, 24, 48, 72 h
Result:	Showed effective inhibition of the MAPK pathway at 4 h, comparable rapid and robust reactivation of RAS-MAPK signaling was observed, such that phospho-ERK levels returned to an average of ~75% of baseline levels by just 72 h. Adaptive feedback is likely to be a key driver of resistance.

In Vivo

In preclinical tumor models, Sotorasib (AMG-510) rapidly and irreversibly binds to KRAS G12C, providing durable suppression of the mitogen-activated protein kinase (MAPK) signaling pathway. Sotorasib (orally; once daily) is capable of inducing tumor regression in mouse models of KRAS G12C cancer^[3].
Sotorasib (AMG-510) (30 mg/kg; p.o.; daily for 28 days) reduces tumor size in NCI-H358 cell-derived xenografts mice model, and has a synergistic effect with Cisplatin^[5].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	Balb/C nude mice (injected with H358 cells under the skin)^[5]
Dosage:	30 mg/kg
Administration:	Oral gavage (p.o.); daily for 28 days
Result:	The mean tumor volume were 426.66mm³. Reduced tumor size, and had a synergistic effect with Cisplatin. Had little effects on body weight.

Clinical Trial

Molecular Weight

560.59

Formula

C₃₀H₃₀F₂N₆O₃

CAS No.

2296729-00-3

Appearance

Solid

Color

White to yellow

SMILES

O=C(C=C)N1C[C@H](C)N(C2=NC(N(C3=C(C)C=CN=C3C(C)C)C4=C2C=C(F)C(C5=C(O)C=CC=C5F)=N4)=O)CC1

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

-20°C, stored under nitrogen

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

Solvent & Solubility

In Vitro:

DMSO : 50 mg/mL (89.19 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

H₂O : 33.33 mg/mL (59.46 mM; ultrasonic and adjust pH to 11 with NaOH)

Preparing
Stock Solutions

Concentration Solvent Mass	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

View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.08 mg/mL (3.71 mM); Clear solution

This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 2

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.08 mg/mL (3.71 mM); Clear solution

This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.08 mg/mL (3.71 mM); Clear solution

This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 900 μL Corn oil, and mix evenly.

For the following dissolution methods, please prepare the working solution directly. It is recommended to prepare fresh solutions and use them promptly within a short period of time.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 20% HP-β-CD in Saline
Solubility: 10 mg/mL (17.84 mM); Suspended solution; Need ultrasonic

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Calculation results:

Working solution concentration: mg/mL

This product has good water solubility, please refer to the measured solubility data in water/PBS/Saline for details.

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only.If necessary, please contact MedChemExpress (MCE).

Purity & Documentation

Purity: 99.94%

Data Sheet (285 KB) SDS (393 KB)

COA (255 KB) HNMR (304 KB) LCMS (265 KB) Elemental Analysis Report (112 KB)

Handling Instructions (2659 KB)

References

[1]. Marwan Fakih, et al, Phase 1 study evaluating the safety, tolerability, pharmacokinetics (PK), and efficacy of AMG 510, a novel small molecule KRASG12Cinhibitor, in advanced solid tumors. Journal of Clinical Oncology.

[2]. Karen Rex, et al. Abstract 3090: In vivo characterization of AMG 510 - a potent and selective KRASG12Ccovalent small molecule inhibitor in preclinical KRASG12Ccancer models. Experimental and Molecular Therapeutics.

[3]. Canon J, et al. The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity. Nature. 2019 Nov;575(7781):217-223. [Content Brief]

[4]. Brian A. Lanman, et al.Abstract 4455: Discovery of AMG 510, a first-in-human covalent inhibitor of KRASG12C for the treatment of solid tumors. Cancer Chemistry.

[5]. Wu LL, et al. AMG-510 and cisplatin combination increases antitumor effect in lung adenocarcinoma with mutation of KRAS G12C: a preclinical and translational research. Discov Oncol. 2023 Jun 7;14(1):91. [Content Brief]

[6]. Ryan MB, et al. KRASG12C-independent feedback activation of wild-type RAS constrains KRASG12C inhibitor efficacy. Cell Rep. 2022 Jun 21;39(12):110993. [Content Brief]

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Cat# HY-114277-10mg

Contact local distributor :

Brand : MedChemExpress

Contact local distributor :

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