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Purity: ≥98%
CCT196969 (CCT-196969) is a novel, orally bioavailable pan-RAF inhibitor with anti-SRC and anticancer activity (IC50 = 0.1 μM). B-RafV600E is directly inhibited by the well-tolerated B-Raf inhibitor CCT196969 in living cells. B-Raf is blocked by CCT196969 at 100 nM and B-RafV600E at 40 nM. At 12 nM, it inhibits CRaf; at 26 nM, SRC; and at 14 nM, LCK. Cell lines with B-Raf mutations in melanoma and colorectal cancer are susceptible to CCT196969. The fact that CCT196969 causes caspase 3 and PARP cleavage indicates that it causes apoptosis. In BRAF and NRAS mutant melanoma, CCT196969 does not promote paradoxical pathway activation and inhibit MEK/ERK. Melanoma cells and xenografts made from patients that are resistant to BRAF and BRAF/MEK inhibitors are inhibited by it. Thus, first-line therapy for BRAF and NRAS mutant melanomas and second-line therapy for patients who develop resistance could both be achieved with paradox-breaking pan-RAF inhibitors that also inhibit SFKs.
| Targets |
B-Raf (V600E) (IC50 = 0.04 μM); Braf (IC50 = 0.1 μM); CRAF (IC50 = 0.01 μM); LCK (IC50 = 0.02 μM); SRC (IC50 = 0.03 μM)
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| ln Vitro |
CCT196969 is a pan-Raf inhibitor with anti-SRC activity. CCT196969 is a B-Raf inhibitor that can be taken orally and is well tolerated. It blocks B-RafV600E in cells directly. B-Raf is blocked by CCT196969 at 100 nM and B-RafV600E at 40 nM. At 12 nM, it inhibits CRaf; at 26 nM, SRC; and at 14 nM, LCK. Cell lines with B-Raf mutations in melanoma and colorectal cancer are susceptible to CCT196969. Caspase 3 and PARP cleavage are induced by CCT196969, indicating that it causes apoptosis[1].
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| ln Vivo |
CCT196969 is incredibly well tolerated and has no detectable negative effects in living organisms. In nude mice, it prevents the growth of NRAS mutant DO4 tumor xenografts. Without resulting in body weight loss in the mice, CCT196969 inhibits ERK and SRC and causes tumor regression in a PDX from the resistant tumor[1].
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| Enzyme Assay |
CCT-196969, a pan-Raf inhibitor, inhibits B-Raf with an IC50 of 0.1 μM.
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| Cell Assay |
Cultured cells are seeded into 96-well plates (2,000 cells per well). B-Raf inhibitors PLX4720 and SB590885, MEK inhibitor PD184352, or compounds CCT241161 and CCT196969 are serially diluted and added 24 hours later. Viability is assessed using CellTiter-Glo assays after a further 72 hours of incubation. After background subtraction, the relative survival in drug-infused environments is normalized to the untreated controls[1].
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| Animal Protocol |
Mice: Female naked mice have tumors established. Daily oral gavage with vehicle (5% DMSO, 95% water), 90 mg/kg PLX4720, 20 mg/kg CCT196969, or 20 mg/kg CCT241161 is the recommended method of treatment. Without a weekend break, all inhibitors are administered seven days a week. Tumor length, width, and depth are measured using calipers, and volume is calculated using the formula volume = 0.5236lengthwidthdepth (in millimeters)[1].
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| References |
| Molecular Formula |
C27H24FN7O3
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| Molecular Weight |
513.52
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| Exact Mass |
513.19
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| Elemental Analysis |
C, 63.15; H, 4.71; F, 3.70; N, 19.09; O, 9.35
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| CAS # |
1163719-56-9
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| Related CAS # |
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| Appearance |
Solid powder
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| SMILES |
CC(C)(C)C1=NN(C(=C1)NC(=O)NC2=C(C=C(C=C2)OC3=C4C(=NC=C3)NC(=O)C=N4)F)C5=CC=CC=C5
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| InChi Key |
KYYKGSDLXXKQCR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C27H24FN7O3/c1-27(2,3)21-14-22(35(34-21)16-7-5-4-6-8-16)32-26(37)31-19-10-9-17(13-18(19)28)38-20-11-12-29-25-24(20)30-15-23(36)33-25/h4-15H,1-3H3,(H,29,33,36)(H2,31,32,37)
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| Chemical Name |
1-(5-tert-butyl-2-phenylpyrazol-3-yl)-3-[2-fluoro-4-[(3-oxo-4H-pyrido[2,3-b]pyrazin-8-yl)oxy]phenyl]ure
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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 (4.05 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 (4.05 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 (4.05 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9473 mL | 9.7367 mL | 19.4734 mL | |
| 5 mM | 0.3895 mL | 1.9473 mL | 3.8947 mL | |
| 10 mM | 0.1947 mL | 0.9737 mL | 1.9473 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.
 CCT196969 and CCT241161 Are BRAF Inhibitors.Cancer Cell.2015 Jan 12;27(1):85-96. |
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 CCT196969 and CCT241161 Inhibit RAS Mutant Cells.
CCT196969 and CCT241161 Inhibit Tumors with Acquired Resistance to Dabrafenib plus Trametinib.Cancer Cell.2015 Jan 12;27(1):85-96. |
 CCT196969 and CCT241161 Inhibit SFK in Patient-Derived Resistant Cells.Cancer Cell.2015 Jan 12;27(1):85-96. |
 CCT196969 and CCT241161 Inhibit Tumors with Acquired Resistance to Vemurafenib.Cancer Cell.2015 Jan 12;27(1):85-96. |
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 CCT196969 and CCT241161 Inhibit PDX from a Patient with Intrinsic Resistance to Vemurafenib.Cancer Cell.2015 Jan 12;27(1):85-96. |
 Model Showing Targets of Vemurafenib, Dabrafenib, Trametinib, CCT196969, and CCT241161.Cancer Cell.2015 Jan 12;27(1):85-96. |
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