| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg | |||
| Other Sizes |
| Targets |
KRAS G12C mutant protein. KRAS G12C inhibitor 15 is a potent inhibitor of the KRAS G12C protein, targeting the mutant glycine-to-cysteine substitution at codon 12. By binding to the mutant protein, it locks KRAS in its inactive GDP-bound state, blocking downstream oncogenic signaling.
|
|---|---|
| ln Vitro |
KRAS G12C inhibitor 15 inhibits KRAS G12C with an IC₅0 of 5 nM. The compound shows potent activity against the KRAS G12C mutant protein and is designed to selectively bind to the mutant form over wild-type KRAS. It has applications in cancer research, particularly for NSCLC.
|
| ln Vivo |
In vivo, KRAS G12C inhibitor 15 would be expected to demonstrate antitumor efficacy in xenograft models of KRAS G12C-mutant cancers. By inhibiting the mutant KRAS protein, the compound blocks downstream signaling pathways (e.g., MAPK, PI3K) and suppresses tumor growth. Efficacy would be assessed in NSCLC and other KRAS G12C-driven tumor models.
|
| Enzyme Assay |
KRAS G12C biochemical activity is measured using a nucleotide exchange assay or a binding assay. Recombinant KRAS G12C protein is incubated with a fluorescently labeled GDP/GTP analog and serial dilutions of test compound. The displacement of the nucleotide analog or the inhibition of SOS-mediated nucleotide exchange is quantified, and IC₅0 values are calculated from dose-response curves.
|
| Cell Assay |
KRAS G12C-mutant cancer cell lines (e.g., NSCLC cell lines with G12C mutation such as NCI-H358 or MIA PaCa-2) are treated with KRAS G12C inhibitor 15 at various concentrations. Cell viability is assessed using MTT or CellTiter-Glo assays. ERK phosphorylation (p-ERK) is measured by Western blotting as a readout of pathway inhibition. Cell cycle and apoptosis are evaluated by flow cytometry.
|
| Animal Protocol |
Mice bearing subcutaneous xenografts of KRAS G12C-mutant cancer cells are administered KRAS G12C inhibitor 15 orally or intraperitoneally. Tumor growth is monitored by caliper measurements. Tumors are harvested for pharmacodynamic analysis of KRAS pathway inhibition (p-ERK, p-AKT) and apoptosis markers. Efficacy is determined by tumor growth inhibition and survival.
|
| ADME/Pharmacokinetics |
KRAS G12C inhibitor 15 has a molecular weight of 498.91 g/mol and formula C2₅H21ClF2N4O3. Standard PK parameters (half-life, Cmax, AUC, clearance, volume of distribution, oral bioavailability) would be determined in rodent studies following IV and PO administration. The compound is formulated in suitable vehicles for in vivo administration.
|
| Toxicity/Toxicokinetics |
Toxicology data for KRAS G12C inhibitor 15 are not publicly available. Standard preclinical safety assessment would include cytotoxicity screening, hERG channel inhibition testing, and repeat-dose toxicology studies in rodents. Given the role of KRAS in normal cell function, potential on-target toxicities would be evaluated.
|
| References | |
| Additional Infomation |
KRAS G12C inhibitor 15 is a research compound for cancer studies. It is not clinically approved. The compound is based on patent WO2019110751A1 (compound 22). It is useful for studying KRAS G12C biology and developing novel therapies for KRAS-mutant cancers, particularly NSCLC. KRAS G12C represents a major therapeutic target in oncology.
|
| Molecular Formula |
C25H21CLF2N4O3
|
|---|---|
| Molecular Weight |
498.91
|
| Exact Mass |
498.127
|
| CAS # |
2349393-21-9
|
| PubChem CID |
138678754
|
| Appearance |
White to yellow solid powder
|
| LogP |
3.9
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
2
|
| Heavy Atom Count |
35
|
| Complexity |
867
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
C(=C)C(N1C[C@@]2([H])N(C3C4C(N=CC=3N(C)C2=O)=C(F)C(C2=C(F)C=CC=C2O)=C(Cl)C=4)C[C@H]1C)=O |c:23,26,28,t:11,31|
|
| InChi Key |
XDVMVEOFPVCHEL-SJKOYZFVSA-N
|
| InChi Code |
InChI=1S/C25H21ClF2N4O3/c1-4-19(34)31-11-17-25(35)30(3)16-9-29-23-13(24(16)32(17)10-12(31)2)8-14(26)20(22(23)28)21-15(27)6-5-7-18(21)33/h4-9,12,17,33H,1,10-11H2,2-3H3/t12-,17-/m1/s1
|
| Chemical Name |
(4R,7R)-16-chloro-14-fluoro-15-(2-fluoro-6-hydroxyphenyl)-4,9-dimethyl-5-prop-2-enoyl-2,5,9,12-tetrazatetracyclo[8.8.0.02,7.013,18]octadeca-1(10),11,13,15,17-pentaen-8-one
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ~193.33 mg/mL (~387.50 mM)
|
|---|---|
| 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 | 2.0044 mL | 10.0218 mL | 20.0437 mL | |
| 5 mM | 0.4009 mL | 2.0044 mL | 4.0087 mL | |
| 10 mM | 0.2004 mL | 1.0022 mL | 2.0044 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
