| Size | Price | |
|---|---|---|
| 5mg | ||
| Other Sizes |
| Targets |
IC50: 56 nM(B-RAF), 7 nM(B-RAFv600E), 5 nM(C-RAF)[1].
Pan-RAF (B-RAF, B-RAF-V600E, C-RAF) |
|---|---|
| ln Vitro |
Belvarafenib (Example 116) is a powerful pan-RAF inhibitor that exhibits anti-tumor properties. Belvarafenib's IC50 values for B-RAF, B-RAFv600E, and C-RAF are 56 nM, 7 nM, and 5 nM, respectively. Additionally, it exhibits strong inhibitory effect against the kinases FMS, DDR1, and DDR2, with IC50 values of 10 nM, 23 nM, and 44 nM, respectively[1].
Belvarafenib TFA potently inhibits B‑RAF, B‑RAF‑V600E, and C‑RAF with IC₅0 values of 56 nM, 7 nM, and 5 nM, respectively. It effectively suppresses MAPK pathway activity in cells harboring various RAF and RAS mutations, and has shown anti‑proliferative effects in a broad range of cancer cell lines. |
| ln Vivo |
Belvarafenib (parent compound) has been evaluated in preclinical models of BRAF‑mutant melanoma, KRAS‑mutant NSCLC, and other RAF‑driven cancers. It demonstrated significant tumor growth inhibition in xenograft models and has advanced to clinical trials. Belvarafenib TFA is expected to have similar in vivo activity.
|
| Enzyme Assay |
For non‑cellular assays, recombinant B-RAF, B-RAF-V600E, and C-RAF proteins are incubated with belvarafenib (0.01‑1000 nM) in the presence of ATP and a substrate. Kinase activity is measured by quantifying substrate phosphorylation. IC₅0 values are calculated from dose‑response curves. The TFA salt form is used for improved solubility.
|
| Cell Assay |
Belvarafenib TFA is dissolved in DMSO and diluted in cell culture media (final DMSO ≤0.1%). BRAF‑V600E mutant melanoma cells (e.g., A375, SK-MEL-28) or KRAS‑mutant cells are treated with belvarafenib (0.1‑1000 nM) for 2‑24 h. pERK levels are measured by Western blotting, and cell proliferation is assessed using MTT or CellTiter-Glo assays.
|
| Animal Protocol |
Belvarafenib has been evaluated in mouse xenograft models of BRAF‑mutant melanoma and KRAS‑mutant NSCLC. The compound is formulated in a suitable vehicle (e.g., 0.5% methylcellulose or 10% DMSO/40% PEG400/5% Tween 80) and administered orally once or twice daily at doses of 10‑50 mg/kg. Tumor growth inhibition, PK/PD, and target engagement are assessed.
|
| ADME/Pharmacokinetics |
No PK data for belvarafenib TFA has been reported. However, belvarafenib (parent compound) is orally bioavailable with moderate plasma half‑life and tissue distribution. The TFA salt form is used to improve solubility and dissolution rate. Detailed PK parameters are available in clinical study reports.
|
| Toxicity/Toxicokinetics |
No toxicity data for belvarafenib TFA has been reported. As a pan‑RAF inhibitor, potential toxicities may include skin rash, hyperkeratosis, gastrointestinal effects, and fatigue, consistent with class‑related adverse events. The safety profile of belvarafenib is being evaluated in ongoing clinical trials.
|
| References | |
| Additional Infomation |
Belvarafenib TFA (CAS: 2443966-84-3; formula: C2₅H1₇ClF4N₆O3S; MW: 592.95) is the TFA salt of belvarafenib, a pan‑RAF inhibitor that has advanced to clinical trials for RAF‑ and RAS‑driven cancers (NCT number not disclosed). It represents a promising next‑generation RAF inhibitor designed to overcome resistance mechanisms associated with first‑generation BRAF inhibitors.
|
| CAS # |
2443966-84-3
|
|---|---|
| Related CAS # |
Belvarafenib;1446113-23-0
|
| Appearance |
White to off-white solid powder
|
| 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 Note: Please store this product in a sealed and protected environment, 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) |
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
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.) |
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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