Physicochemical Properties
| Molecular Formula | C35H38FN7O2 |
| CAS # | 2821863-70-9 |
| Related CAS # | 2821863-70-9 |
| Appearance | Typically exists as solid at room temperature |
| Synonyms | KRAS G12C inhibitor 57 |
| 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 |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | KRAS(G12C) (DC50 = 0.21 μM) |
| ln Vitro | KRAS G12C Inhibitor 57 (Compound 50) (0-10 μM; 3 days) exhibits robust reduction of downstream signaling and worldwide inhibition of KRAS and KRAS-driven cell lines [1]. H358 tumor cell drift is inhibited by KRAS G12C Inhibitor 57 (0.1-1 μM); this inhibitor acts over a 48-hour period [1]. |
| ln Vivo | The KRAS G12C inhibitor 57 (Compound 50) (10 and 30 mg/kg; oral; daily for 20 days) proved resistant to the H358 xenograft tumor model. Pharmacokinetic data of KRAS G12C inhibitor 57 (compound 50) in ICR mice. [1] Parameter iv (3 mg/kg) Parameter po (30 mg/kg) AUC(0−t) (h*ng/mL) 801 AUC(0−t) (h*ng/mL) 600 AUC(0 −∞) (h*ng/mL) 804 AUC(0−∞) (h*ng/mL) 835 C0 (ng/mL) 1964 Cmax (ng/mL) 316 T1/2 (h) 0.930 T1/2 ( h) 4.79 Vss (L/kg) 4.98 Tmax (h) 0.083 CL (mL/h/kg) 3739 F (%) 10.4 AUCo-inf (h*mg/mL) 7060 ± 1020 (14.5%) 21800 ± 2310 ( 10.6%) 101000 ± 16700 (16. |
| Cell Assay |
Western blot analysis[1] Cell Types: H358 (KRAS p. G12C; 24 h) induces liver cancer in H358 cells[1]. ) Cell Tested Concentrations: 0, 0.1, 0.3, 0.5, 1 and 5 μM Incubation Duration: 4 and 24 hrs (hours) Experimental Results: Dose- and time-dependent inhibition of active KRAS-GTP and phosphorylation of ERK and AKT (MAPK and PI3K pathways) way, and has a strong inhibitory effect on ERK phosphorylation at a concentration of 0.1 μM. Increased cleavage of PARP and induction of caspase-7 (24 hrs (hours)). Western Blot Analysis[1] Cell Types: H1975 Cell Line Tested Concentrations: 5, 10 and 20 μM Incubation Duration: 4 hrs (hours) Experimental Results: Disruption of ERK phosphorylation. Cell proliferation assay[1] Cell Types: H358 cells containing KRAS p.G12C, MIA Paca2 cells containing KRAS p.G12C, H1975 cells containing KRAS p.WT and A549 cells containing KRAS p.G12S Tested Concentrations: 0-10 μM Incubation Duration: 3 days Experimental Results: demonstrated good inhibitory activity against H358 cells and MIA Paca2 cells, with IC50 values of 0.16 μM and 0.87 μM, but no obvious inhibito |
| Animal Protocol |
Animal/Disease Models: BALB/c-nu/nu (nude) mice, H358 xenograft model [1] Doses: 10 mg/kg and 30 mg/kg Route of Administration: Orally, one time/day, Results lasting 20 days: Significant tumor growth inhibition in a dose-dependent manner, with significant tumor regression at the 30 mg/kg dose (tumor growth inhibition, TGI = 84.0%). All dose groups were well tolerated with no weight loss or morphological damage to internal organs including the heart, spleen, and kidneys. Oral administration of 10 mg/kg and 30 mg/kg Dramatically inhibited the phosphorylation of ERK and AKT in tumors of nude mice. Animal/Disease Models: ICR mice [1] Doses: 3 mg/kg or 30 mg/kg Route of Administration: IV or PO (pharmacokinetic/PK/PK analysis) Experimental Results: Administration via iv demonstrated reasonable clearance and half-life. Shows moderate oral bioavailability (F) of 10.4%. |
| References | [1]. Song Z, et al. Identification of novel Pyrrolo [2, 3-d] Pyrimidine-based KRAS G12C inhibitors with anticancer effects. European Journal of Medicinal Chemistry, 2022: 114907. |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| 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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |