HY-114277-5mg | Sotorasib [2296729-00-3] Clinisciences

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 is the first KRAS G12C inhibitor in clinical development and leads to the regression of KRAS G12C tumors^[1]^[2].

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].

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).

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].

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

Essai clinique

Masse moléculaire

560.59

Formule

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

Livraison

Room temperature in continental US; may vary elsewhere.

Stockage

-20°C, stored under nitrogen

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

Solvant et solubilité

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.

Calculateur de molarité
Calculateur de dilution

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

Concentration _(start)

Volume _(start)

Concentration _(final)

Volume _(final)

In Vivo:

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:

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(per animal)

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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).

Pureté et documentation

Purity: 99.94%

Select Batch:

SDS (393 KB)

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

Instruction de manipulation (2659 KB)

Références

[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.

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg

H₂O / DMSO	1 mM	1.7838 mL	8.9192 mL	17.8383 mL	44.5959 mL
	5 mM	0.3568 mL	1.7838 mL	3.5677 mL	8.9192 mL
	10 mM	0.1784 mL	0.8919 mL	1.7838 mL	4.4596 mL
	15 mM	0.1189 mL	0.5946 mL	1.1892 mL	2.9731 mL
	20 mM	0.0892 mL	0.4460 mL	0.8919 mL	2.2298 mL
	25 mM	0.0714 mL	0.3568 mL	0.7135 mL	1.7838 mL
	30 mM	0.0595 mL	0.2973 mL	0.5946 mL	1.4865 mL
	40 mM	0.0446 mL	0.2230 mL	0.4460 mL	1.1149 mL
	50 mM	0.0357 mL	0.1784 mL	0.3568 mL	0.8919 mL
DMSO	60 mM	0.0297 mL	0.1487 mL	0.2973 mL	0.7433 mL
DMSO	80 mM	0.0223 mL	0.1115 mL	0.2230 mL	0.5574 mL

* 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.

Sotorasib Related Classifications

GPCR/G Protein MAPK/ERK Pathway
Ras

Sotorasib [2296729-00-3]

Referentie HY-114277-5mg

Neem contact op met een lokale distributeur :

Merk : MedChemExpress

Neem contact op met een lokale distributeur :

Other Forms of Sotorasib:

Voir tous les produits spécifiques à Isoform Ras:

Calculateur de molarité

Calculateur de dilution

Complete Stock Solution Preparation Table

Sotorasib Related Classifications

Keywords:

Misschien heeft u ook interesse in de volgende producten:

Sotorasib [2296729-00-3]

Referentie HY-114277-5mg

Neem contact op met een lokale distributeur :

Merk : MedChemExpress

Neem contact op met een lokale distributeur :

Other Forms of Sotorasib:

Voir tous les produits spécifiques à Isoform Ras:

Sotorasib Related Antibodies

Calculateur de molarité

Calculateur de dilution

Complete Stock Solution Preparation Table

Sotorasib Related Classifications

Keywords:

Misschien heeft u ook interesse in de volgende producten: