CCT-241161 is a novel potent and orally bioactive pan-RAF inhibitor with anticancer activity. It inhibits RAF with IC50s of 3, 6, 10, 15 and 30 nM for LCK, CRAF, SRC, V600E-BRAF and BRAF, respectively.
Physicochemical Properties
| Molecular Formula | C28H27N7O3S |
| Molecular Weight | 541.62 |
| Exact Mass | 541.189 |
| CAS # | 1163719-91-2 |
| PubChem CID | 44132853 |
| Appearance | Typically exists as solid at room temperature |
| Density | 1.4±0.1 g/cm3 |
| Index of Refraction | 1.692 |
| LogP | 5.1 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 7 |
| Rotatable Bond Count | 7 |
| Heavy Atom Count | 39 |
| Complexity | 893 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | N(C1=CC=C(OC2=C3N=CC(=O)NC3=NC=C2)C=C1SC)C(NC1N(C2=CC=CC=C2)N=C(C(C)(C)C)C=1)=O |
| InChi Key | DPMYVVGAYAPQNS-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C28H27N7O3S/c1-28(2,3)22-15-23(35(34-22)17-8-6-5-7-9-17)32-27(37)31-19-11-10-18(14-21(19)39-4)38-20-12-13-29-26-25(20)30-16-24(36)33-26/h5-16H,1-4H3,(H,29,33,36)(H2,31,32,37) |
| Chemical Name | 1-(5-tert-butyl-2-phenylpyrazol-3-yl)-3-[2-methylsulfanyl-4-[(3-oxo-4H-pyrido[2,3-b]pyrazin-8-yl)oxy]phenyl]urea |
| Synonyms | CCT 241161 CCT-241161 CCT241161 |
| 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
| ln Vitro | In WM266.4 cells, CCT241161 (1, 3, 10, 30, 100 nM; 24 h) suppresses MEK and ERK[1]. In Ba/F3 cells, CCT241161 (1, 10, 100 nM and 1, 10, 100 µM) suppresses BRAFV600E[1]. A375 cells are inhibited by CCT241161 (0.5 µM; 20 days), however drug resistance is not produced[1]. Melanoma cells resistant to BRAF inhibitors are inhibited by CCT241161 (1 µM, 4 h)[1]. In NRAS mutant cells, CCT241161 (0.1, 0.3, 1, 3, 10 µM; 24 h) suppresses MEK[1]. In D04 cells, CCT241161 (0.1, 1, 10, 100 µM) has anti-proliferative activity[1]. |
| ln Vivo | CCT241161 (10, 20 mg/kg; ig; once daily for 7 days) prevents the formation of tumor xenografts in mice that are BRAF mutant A375, PLX4720-resistant A375, and NRAS mutant DO4[1]. |
| Cell Assay |
Cell Viability Assay[1] Cell Types: WM266.4 cells (BRAF mutant) Tested Concentrations: 1, 3, 10, 30, 100 nM Incubation Duration: 24 h Experimental Results: demonstrated effects of inhibiting MEK and ERK in WM266.4 cells. Cell Viability Assay[1] Cell Types: Ba/F3 cells Tested Concentrations: 1, 10, 100 nM and 1, 10, 100 µM Incubation Duration: Experimental Results: Inhibited BRAF-V600E and BRAF-T529N, V600E in Ba/F3 cells. Cell Viability Assay[1] Cell Types: A375 cell Tested Concentrations: 0.5 µM Incubation Duration: 20 days Experimental Results: Maintained inhibitory activity against A375 cell ,without drug resistance in 20 days. Cell Proliferation Assay[1] Cell Types: D04 cells Tested Concentrations: 0.1, 1, 10, 100 µM Incubation Duration: Experimental Results: Efficiently inhibited NRAS mutant cell growth. Western Blot Analysis[1] Cell Types: patient #2 (PLX4720-resistant cells from patient with vemurafenib-resistant melanoma) Tested Concentrations: 1 µM Incubation Duration: 4 h Experimental Results: Inhibited MEK, ERK, and SRC in the cells from patient #2. Western Blot Analysis[1] Cell Types: D04 cells Tested Concentrations: |
| Animal Protocol |
Animal/Disease Models: Female nude mice (5 to 6- week-old)[1]. Doses: 10, 20 mg/kg Route of Administration: po (oral gavage); one time/day for 7 days. Experimental Results: demonstrated activity of tumor regression in nude mice with xenografts tumor of BRAF mutant A375, PLX4720 -resistant A375 (A375/R) and NRAS mutant DO4, without causing any body weight loss to the mice. |
| References |
[1]. Paradox-breaking RAF inhibitors that also target SRC are effective in drug-resistant BRAF mutant melanoma. Cancer Cell. 2015 Jan 12;27(1):85-96. |
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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8463 mL | 9.2316 mL | 18.4631 mL | |
| 5 mM | 0.3693 mL | 1.8463 mL | 3.6926 mL | |
| 10 mM | 0.1846 mL | 0.9232 mL | 1.8463 mL |