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Purity: ≥98%
ARS-1620 is a novel, potent, orally bioavailable and covalent inhibitor of KRASG12C with antitumor activity. It is highly selective and potent against KRASG12C. A new class of KRASG12C-specific inhibitors, ARS-1620, shows promise as a treatment.
| Targets |
KRAS(G12C)
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| ln Vitro |
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| ln Vivo |
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| Enzyme Assay |
In p.G12C mutant cancer cells, ARS-1620 covalently and with high potency selectively inhibits KRAS (G12C) activity. In line with its covalent mechanism of inhibition, ARS-1620 quickly engaged G12C in a concentration- and time-dependent manner. ARS-1620 showed near complete engagement at 3.0 μM and half maximal G12C target engagement (TE50) at ~0.3 μM after 2 hours of treatment, when compared to a panel of cell lines carrying the mutant variant. In H358 (p.G12C), but not in negative control lung cancer cell lines lacking p.G12C (A549, H460, and H441), RS-1620 selectively and dose-dependently inhibits RAS-GTP and the phosphorylation of MEK, ERK, RSK, S6, and AKT. The potency of ARS-1620 is sub-micromolar allele-specific (IC50 = 0.3 μM; IC90 = 1 μM). Cys-12 is covalently modified by ARS-1620 to mediate its activity, which is exclusive to the G12C allele.
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| Cell Assay |
After being seeded into 24 well ULA-plates, 5×104 cells are left to rest for the entire night. After that, DMSO or ARS-1620 are applied to the cells. After two treatment days, the amount of apoptosis and cell death is assessed using flow cytometry to measure the percentage of sub-diploid events and DNA content (cell cycle) or by staining with annexin V-APC and prodidium iodide or 70% ethanol fixation followed by FxCycle Violet staining[1].
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| Animal Protocol |
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| Additional Infomation |
ARS-1620 is a qinazoline derivative carrying chloro and fluoro substituents at positions 6 and 8 respectively, a 2-fluoro-6-hydroxyphenyl group at position 7, and a 4-(prop-2-enoyl)piperazin-1-yl group at position 4. A potent, selective, and orally bioavailable covalent KRAS-G12C inhibitor, it inhibits the protein coding gene KRAS (Kirsten rat sarcoma virus) with high potency in cells and animals. It has a role as an inhibitor, an antiviral agent and an antineoplastic agent.
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| Molecular Formula |
C21H17CLF2N4O2
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| Molecular Weight |
430.8351
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| Exact Mass |
430.1
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| Elemental Analysis |
C, 58.54; H, 3.98; Cl, 8.23; F, 8.82; N, 13.00; O, 7.43
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| CAS # |
1698055-85-4
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| Related CAS # |
ARS-1323; 1698024-73-5; ARS-1630; 1698055-86-5
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| PubChem CID |
137003167
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| Appearance |
Off-white to light yellow solid powder
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| 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 |
3
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| Heavy Atom Count |
30
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| Complexity |
636
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
ZRPZPNYZFSJUPA-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H17ClF2N4O2/c1-2-16(30)27-6-8-28(9-7-27)21-12-10-13(22)17(19(24)20(12)25-11-26-21)18-14(23)4-3-5-15(18)29/h2-5,10-11,29H,1,6-9H2
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| Chemical Name |
1-[4-[6-chloro-8-fluoro-7-(2-fluoro-6-hydroxyphenyl)quinazolin-4-yl]piperazin-1-yl]prop-2-en-1-one
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.83 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.83 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.83 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 5%DMSO + 40%PEG300 + 5%Tween 80 + 50%ddH2O: 4.3mg/ml (9.98mM) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3210 mL | 11.6052 mL | 23.2105 mL | |
| 5 mM | 0.4642 mL | 2.3210 mL | 4.6421 mL | |
| 10 mM | 0.2321 mL | 1.1605 mL | 2.3210 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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