ARS-1620 |
Catalog No.GC34055
One-Click Copy Product Info
|
ARS-1620 is a highly selective, orally active inhibitor of the KRAS p.G12C mutant protein.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1698055-85-4
Sample solution is provided at 25 µL, 10mM.
_1-3.$$$39978408@51.jpg');)
_1-9.$$$38538795@65.jpg');)
_1-9.$$$39112701@51.jpg');)
_1-7.$$$37316672@70.jpg');)
_366-372.$$$36198801@70.jpg');)
.$$$38565142@65.jpg');)
_1867-1883.$$$33248023@67.jpg');)
_eads6055.$$$39977546@45.jpg');)
_eadm9805.$$$40080571@45.jpg');)
_eadj3020.$$$39666821@45.jpg');)
_1-20.$$$39757301@28.jpg');)
_1-24.$$$38898113@28.jpg');)
_273-287.$$$36806353@46.jpg');)
_1-16.$$$37156877@44.jpg');)
_1-19.$$$37460805@44.jpg');)
_1291-1307.$$$34518654@46.jpg');)
ARS-1620 is a highly selective, orally active inhibitor of the KRAS p.G12C mutant protein[1-2]. ARS-1620 irreversibly and covalently binds to the GDP-bound form of the KRAS G12C protein at the Switch-II pocket, locking KRAS in an inactive state and thereby blocking downstream signaling transduction. ARS-1620 is applicable to the study of non-small cell lung cancer, colorectal cancer, pancreatic cancer, and other solid tumors harboring the KRAS p.G12C mutation[3-4].
In vitro, ARS-1620 (1µM) was used to treat three non-small cell lung cancer cell lines with the KRAS G12C mutation and varying drug sensitivities (H358, Calu1, H1792) for 6 and 24 hours. ARS-1620 significantly inhibited the activity of the MAPK and AKT signaling pathways and activated the ERBB2/3 signaling pathway [5]. ARS-1620 (0-1µM) was also applied to three KRAS G12C-mutant lung cancer cell lines (H23, HOP-62, Calu-1) for 14 days. ARS-1620 significantly inhibited colony formation and cell proliferation, and induced a marked upregulation of mTOR gene mRNA expression[6].
In vivo, ARS-1620 (50-400mg/kg; oral gavage; once daily) was administered for 2 to 3 weeks to mice bearing subcutaneous xenograft tumors derived from human non-small cell lung cancer cells (MIA-PaCa2, H358, H2030, H1373, HCC44, LU99A) with the KRAS p.G12C mutation, as well as to mice with patient-derived xenograft (PDX) models harboring the KRAS p.G12C mutation. ARS-1620 significantly inhibited tumor growth and promoted tumor regression[7]. In PDX model mice with the KRAS p.G12C mutation, ARS-1620 (100-200mg/kg; oral gavage; 5 times per week for 3 weeks) induced significant tumor growth inhibition and regression, accompanied by a high degree of KRAS G12C target occupancy and inhibition of downstream signaling pathways (RAS-GTP, p-ERK, p-S6)[8].
References:
[1] Li L, Zhao H, Peng X, et al. Discovery of novel Quinazoline-based KRAS G12C inhibitors as potential anticancer agents. Bioorg Med Chem. 2022 Oct 1;71:116962.
[2] Lin X, Ma Q, Chen L, et al. Identifying genes associated with resistance to KRAS G12C inhibitors via machine learning methods. Biochim Biophys Acta Gen Subj. 2023 Dec;1867(12):130484.
[3] Hansen R, Peters U, Babbar A, et al. The reactivity-driven biochemical mechanism of covalent KRASG12C inhibitors. Nat Struct Mol Biol. 2018 Jun;25(6):454-462.
[4] Shankar S, Tien JC, Siebenaler RF, et al. An essential role for Argonaute 2 in EGFR-KRAS signaling in pancreatic cancer development. Nat Commun. 2020 Jun 4;11(1):2817.
[5] Solanki HS, Welsh EA, Fang B, et al. Cell Type-specific Adaptive Signaling Responses to KRASG12C Inhibition. Clin Cancer Res. 2021 May 1;27(9):2533-2548.
[6] Ito M, Miyata Y, Hirano S, et al. Dual inhibition of GTP-bound KRAS and mTOR in lung adenocarcinoma and squamous cell carcinoma harboring KRAS G12C. Cell Commun Signal. 2025 May 11;23(1):220.
[7] Janes MR, Zhang J, Li LS, et al. Targeting KRAS Mutant Cancers with a Covalent G12C-Specific Inhibitor. Cell. 2018 Jan 25;172(3):578-589.e17.
[8] Molina-Arcas M, Moore C, Rana S, et al. Development of combination therapies to maximize the impact of KRAS-G12C inhibitors in lung cancer. Sci Transl Med. 2019 Sep 18;11(510):eaaw7999.
| Cell experiment [1]: | |
Cell lines | H358, H1792, and Calu1 cells (human non-small cell lung cancer cell lines harboring KRAS G12C mutation) |
Preparation Method | H358, H1792, and Calu1 cells were treated with ARS-1620 at 1μM for 6 hours and 24 hours for phosphoproteomics analysis. Target engagement was confirmed by LC-MRM quantification showing significant reduction of free KRAS G12C peptide signal. |
Reaction Conditions | 1μM; 6h and 24h. |
Applications | ARS-1620 treatment significantly inhibited KRAS downstream signaling, as evidenced by decreased phosphorylation of MAPK/ERK (p-ERK) and, in some lines, AKT (p-AKT). |
| Animal experiment [2]: | |
Animal models | Athymic female nude mice (NCr nu/nu) and CD-1 mice |
Preparation Method | Mice bearing established subcutaneous xenografts of human cancer cell lines (e.g., MIA-PaCa2, H358, H2030, HCC44, H1373, LU99A) or patient-derived xenografts (PDX) harboring KRAS p.G12C were administered ARS-1620 orally (50-400mg/kg; Once daily (q.d.). |
Dosage form | 50-400mg/kg; p.o.; Once daily for 2-3 weeks. |
Applications | In KRAS p.G12C xenograft models (e.g., MIA-PaCa2, H358), ARS-1620 significantly inhibited tumor growth and induced marked tumor regression. In contrast, it had no effect on KRAS p.G12V models. In a panel of KRAS p.G12C patient-derived xenograft (PDX) models, ARS-1620 induced significant tumor growth inhibition and regression following 3 weeks of treatment, while PDX models lacking the G12C mutation showed no response. |
References: | |
| Cas No. | 1698055-85-4 | SDF | |
| Canonical SMILES | C=CC(N1CCN(C2=C3C=C(Cl)[C@@]([C@@]4=C(O)C=CC=C4F)=C(F)C3=NC=N2)CC1)=O.[S] | ||
| Formula | C21H17ClF2N4O2 | M.Wt | 430.84 |
| Solubility | DMSO : ≥ 53 mg/mL (123.02 mM) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 2.321 mL | 11.6052 mL | 23.2105 mL |
| 5 mM | 464.2 μL | 2.321 mL | 4.6421 mL |
| 10 mM | 232.1 μL | 1.1605 mL | 2.321 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
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.)
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 saline, 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.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 22 reference(s) in Google Scholar.)