| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
K-Ras G12C-IN-2 targets the K-Ras G12C mutant protein, which harbors a glycine-to-cysteine substitution at codon 12. The compound covalently binds to the mutant cysteine residue, locking KRAS in an inactive GDP-bound state and preventing downstream signaling. By inhibiting the GTPase activity of the K-Ras G12C protein, the compound blocks the activation of downstream MAPK and PI3K signaling pathways.
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| ln Vitro |
K-Ras G12C-IN-2 is a covalent inhibitor of Kras g12c that was taken from compound V-35 in patent WO2014152588A1[1].
In vitro, K-Ras G12C-IN-2 demonstrates potent and irreversible inhibition of K-Ras G12C mutant protein. The compound covalently modifies the mutant cysteine, preventing the activation of KRAS and downstream signaling. By inhibiting KRAS G12C, the compound suppresses the proliferation of cancer cells harboring this mutation. |
| ln Vivo |
In vivo, K-Ras G12C-IN-2 has the potential to exhibit antitumor activity in preclinical models of KRAS G12C-mutant cancers, such as NSCLC and colorectal cancer. As a covalent inhibitor, it provides sustained target engagement and has the potential for durable efficacy. Preclinical studies are expected to demonstrate its ability to inhibit tumor growth in xenograft models.
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| Enzyme Assay |
In vitro enzyme assays for KRAS G12C inhibition involve incubating recombinant KRAS G12C protein with GDP and varying concentrations of K-Ras G12C-IN-2. The compound's ability to covalently modify the mutant cysteine and inhibit GDP-GTP exchange is measured using fluorescence-based or radioactive assays. IC₅₀ values are calculated from dose-response curves.
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| Cell Assay |
Cellular assays are performed using KRAS G12C-mutant cancer cell lines such as NCI-H358 (NSCLC) or SW837 (colorectal cancer). Cells are treated with K-Ras G12C-IN-2 at various concentrations for 48-72 hours. Cell viability is assessed using MTT or CellTiter-Glo assays. KRAS signaling inhibition is confirmed by Western blot analysis of phospho-ERK and phospho-AKT.
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| Animal Protocol |
In vivo studies are conducted in tumor-bearing mouse models of KRAS G12C-mutant cancers. K-Ras G12C-IN-2 is administered orally or intraperitoneally at various doses. Tumor volume is measured periodically, and tumors are harvested for biomarker analysis, including assessment of phospho-ERK and Ki-67 by immunohistochemistry.
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| ADME/Pharmacokinetics |
K-Ras G12C-IN-2 (molecular weight 418.92, formula C₂₁H₂₇ClN₄O₃) is a small-molecule compound. It is soluble in DMSO (≥22 mg/mL). The compound is typically stored at -20°C. Its physicochemical properties support its use in both in vitro and in vivo studies.
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| Toxicity/Toxicokinetics |
Preclinical toxicity studies of K-Ras G12C-IN-2 have been limited, as the compound is primarily used as a research tool. No significant toxicity has been reported in the available literature. The compound's safety profile supports its use for studying KRAS G12C biology.
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| References | |
| Additional Infomation |
K-Ras G12C-IN-2 is a novel, potent, and irreversible covalent inhibitor of mutant K-Ras G12C. Its mechanism involves covalently binding to the mutant cysteine residue, locking KRAS in an inactive state and inhibiting downstream signaling. The compound is designed to target KRAS G12C, a driver mutation in NSCLC and colorectal cancer. K-Ras G12C-IN-2 is primarily used for research purposes and has not received regulatory approval for clinical use.
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| Molecular Formula |
C21H27CLN4O3
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|---|---|
| Molecular Weight |
418.9171
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| Exact Mass |
418.177
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| CAS # |
1629267-75-9
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| PubChem CID |
86279948
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
675.7±55.0 °C at 760 mmHg
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| Flash Point |
362.4±31.5 °C
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| Vapour Pressure |
0.0±2.2 mmHg at 25°C
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| Index of Refraction |
1.666
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| LogP |
1.59
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
29
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| Complexity |
629
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C=CC(=O)N1CC(C1)N2CCN(CC2)C(=O)CNC3=C(C=C(C(=C3)C4CC4)Cl)O
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| InChi Key |
LTHUJAPYGTUVMD-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H27ClN4O3/c1-2-20(28)26-12-15(13-26)24-5-7-25(8-6-24)21(29)11-23-18-9-16(14-3-4-14)17(22)10-19(18)27/h2,9-10,14-15,23,27H,1,3-8,11-13H2
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| Chemical Name |
1-[3-[4-[2-(4-chloro-5-cyclopropyl-2-hydroxyanilino)acetyl]piperazin-1-yl]azetidin-1-yl]prop-2-en-1-one
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| Synonyms |
K-Ras G12C-IN-2
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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 |
| 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) |
DMSO : ≥ 22 mg/mL (~52.52 mM)
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3871 mL | 11.9355 mL | 23.8709 mL | |
| 5 mM | 0.4774 mL | 2.3871 mL | 4.7742 mL | |
| 10 mM | 0.2387 mL | 1.1935 mL | 2.3871 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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