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ARS-1620 Ras inhibitor

Name: ARS-1620
Brand: Selleck Chemicals
SKU: S8707
Availability: InStock
Rating: 5 (22 reviews)

Cat.No.S8707

ARS-1620 is a potent, orally bioavailable covalent inhibitor of KRAS^G12C and could achieve rapid and sustained in vivo target occupancy to induce tumor regression.

Chemical Structure

Molecular Weight: 430.84

Jump to Mechanism of Action Solubility Chemical Information, Storage & Stability Specificity

Quality Control

Batch: Purity: 99.38%

99.38

Related Targets	DNA/RNA Synthesis CDK Microtubule Associated HSP PD-1/PD-L1 Aurora Kinase Casein Kinase Rho Serine/threonin kinase eIF Chk ROCK Myc Kinesin PLK DHFR PAK PERK DYRK RUNX PP2A PFKFB AP-1 MPS1 Wee1 p21 BMI-1 LIM kinase Nur77 APC
Related Products	Salirasib Adagrasib (MRTX849) ARS-853 BI-3406 MRTX1133 BAY-293 K-Ras(G12C) inhibitor 12 RBC8 Kobe0065 KRpep-2d BQU57 BI-2852 CID-1067700 (ML282) K-Ras(G12C) inhibitor 9 BI-2865 Arf6 Antibody [N23E24] Ras Antibody [P21A20] Alamandine LC-2 (Rac)-Antineoplaston A10 K-Ras-IN-1 Divarasib (GDC-6036) LY3537982 (KRAS G12C inhibitor 19) garsorasib (D-1553) RALA Antibody [F13D3] LY3499446 RMC-6291 APS6-45 SOS1 Antibody [N10K2] MCP110

Chemical Information, Storage & Stability

Molecular Weight	430.84	Formula	C₂₁H₁₇ClF₂N₄O₂	Storage (From the date of receipt)	3 years -20°C powder
CAS No.	1698055-85-4	--		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			Smiles	C=CC(=O)N1CCN(CC1)C2=NC=NC3=C(C(=C(C=C32)Cl)C4=C(C=CC=C4F)O)F

Solubility

In vitro
Batch:

DMSO : 86 mg/mL (199.61 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 86 mg/mL

Water : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
Mass value Mass unit	Concentration value Concentration unit	Volume value Volume unit	Molecular weight (g/mol)

Dilution Calculator Molecular Weight Calculator

In vivo batch selection In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	4.300mg/ml (9.98mM)	Taking the 1 mL working solution as an example, add 50 μL 86 mg/ml clarified DMSO stock solution to 400 μL PEG300, mix evenly to clarify it; add 50 μL Tween80 to the above system, mix evenly to clarify it; then continue to add 500 μL ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg

Average weight of animals: g

Dosing volume per animal: μL

Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO

% Tween 80

% ddH₂O

% DMSO

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Mechanism of Action

Targets/IC₅₀/Ki	K-Ras(G12C) ^[1]
In vitro	ARS-1620 covalently inhibits KRAS (G12C) activity with high potency and atropisomeric selectivity in p.G12C mutant cancer cells. This compound rapidly engaged G12C in a concentration- and time- dependent manner consistent with its covalent mechanism of inhibition. Across a panel of cell lines harboring the mutant allele, it exhibited a half maximal G12C target engagement (TE50) at ~0.3 μM and near complete engagement at 3.0 μM after 2 hr of treatment. This chemical inhibits RAS-GTP and the phosphorylation of MEK, ERK, RSK, S6, and AKT in a dose-dependent and selective manner in H358 (p.G12C) but not in negative control lung cancer cell lines lacking p.G12C (A549, H460, and H441). It elicits sub-micromolar allele-specific potency (IC50 = 0.3 μM; IC90 = 1 μM). The activity of this compound is specific to the G12C allele and mediated by the covalent modification of Cys-12^[1].
In vivo	ARS-1620 exhibits excellent oral bioavailability (F > 60%) in mice. In MIA-PaCa2 xenografts (p.G12C), this compound significantly inhibits tumor growth (p < 0.001) in a dose-dependent manner with marked regression at a dose of 200 mg/kg, given once daily. Xenografts of H441 (p.G12V) lack a response at all doses tested and the R-atropisomer of this chemical lacks activity in both models. It selectively induces tumor regression in patient-derived tumor models (harboring KRAS p.G12C)^[1].
References	[1] https://pubmed.ncbi.nlm.nih.gov/29373830/

Applications

Methods	Biomarkers	Images	PMID
Western blot	RAS-GTP / RAS / pERK / p-S6 / p-AKT / Cleaved-PARP		29373830
Growth inhibition assay	Cell viability		29373830

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