| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
BRAF-V600E < 50 nM (IC50) Braf 50-100 nM (IC50)
The primary target of Uplarafenib is BRAF (B-Raf proto-oncogene, serine/threonine-protein kinase). It specifically targets the BRAF V600E mutation, which is commonly associated with various cancers, including melanoma, colorectal cancer, and non-small cell lung cancer. BRAF is a key component of the RAS/RAF/MEK/ERK signaling pathway. By inhibiting this mutated kinase, Uplarafenib blocks downstream signaling and suppresses tumor growth. |
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| ln Vitro |
Compound C09, uplarafenib, exhibits over 89% inhibition against BRAF and BRAF V600E at 1 μM [1]. Against BRAF, uplarafenib exhibits an IC50 of 50–100 nM, whereas against BRAF V600E, it is less than 50 nM[1]. A375 and SK-MEL-28 cell growth is inhibited by uplarafenib (72 h), whereas CHL-1 and SK-MEL-31 cell growth is unaffected[1].
Uplarafenib is a potent BRAF inhibitor with an IC50 in the range of 50-100 nM. It exhibits antitumor activity and may not affect cell proliferation and differentiation. The compound's selectivity for the BRAF V600E mutation makes it a valuable tool for studying BRAF-mutant cancers. Its IC50 range of 50-100 nM indicates potent inhibitory activity. |
| ln Vivo |
In vivo, Uplarafenib exhibits antitumor activity in models of BRAF-mutant cancers. It is used in research for solid tumors. Its efficacy would be assessed in animal models of melanoma, colorectal cancer, and other BRAF-mutant tumors, with endpoints including tumor growth inhibition, survival, and analysis of MAPK pathway signaling.
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| Enzyme Assay |
In vitro enzyme activity assays for Uplarafenib typically involve measuring its ability to inhibit BRAF kinase activity. Recombinant BRAF enzyme (wild-type or V600E mutant) is incubated with its substrate (MEK) in the presence of ATP and increasing concentrations of Uplarafenib. Kinase activity is measured by detecting phosphorylation of MEK, and the IC50 is determined from the dose-response curve. The reported IC50 range is 50-100 nM.
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: A375, SK-MEL-28, SK-MEL-31 and CHL-1 Tested Concentrations: Incubation Duration: 72 h Experimental Results: demonstrated inhibition with IC50s less than 500 nM against A375 and SK-MEL-28 cells, and demonstrated no inhibition against CHL-1 and SK-MEL-31. Cellular assays for Uplarafenib involve treating BRAF V600E-mutant cancer cell lines with the compound and measuring its effects on cell proliferation, MAPK pathway signaling, and apoptosis. Readouts include inhibition of ERK phosphorylation, reduction of cell viability, and induction of apoptosis. The compound's selectivity for the V600E mutation can be confirmed by testing against wild-type BRAF cells. |
| Animal Protocol |
In vivo efficacy of Uplarafenib would be evaluated in mouse xenograft models of BRAF V600E-mutant cancers. The compound could be administered orally or via injection. Efficacy endpoints would include tumor growth inhibition, survival, and analysis of MAPK pathway signaling in tumor tissue.
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| ADME/Pharmacokinetics |
Uplarafenib has a molecular weight of 494.49 and a molecular formula of C22H21F3N4O4S. It is a potent BRAF inhibitor with an IC50 in the range of 50-100 nM. The compound specifically targets the BRAF V600E mutation. It exhibits antitumor activity and is used in research for solid tumors. It should be stored at -20°C for up to 3 years as a powder. The compound is for research use only and is not intended for human therapeutic use.
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| Toxicity/Toxicokinetics |
No specific toxicity data is available for Uplarafenib in the provided literature. As a research compound, its safety profile would be an important consideration for in vivo applications. Potential toxicities could be related to its effects on MAPK pathway signaling in normal tissues. Standard preclinical safety studies would be required to evaluate its safety for potential therapeutic applications. The compound is for research use only and is not intended for human therapeutic use.
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| References | |
| Additional Infomation |
Uplarafenib is a small molecule drug. The international nonproprietary name prefix "-rafenib" indicates that uplarafenib is a Raf (rapidly accelerated fibrosarcoma) kinase inhibitor. The monoisotopic molecular weight of uplarafenib is 494.12 Da.
Uplarafenib (B-Raf IN 10) is a potent BRAF inhibitor with an IC50 in the range of 50-100 nM. It selectively targets the BRAF V600E mutation, which is commonly associated with various cancers. Uplarafenib has a molecular formula of C22H21F3N4O4S and a molecular weight of 494.49. It exhibits antitumor activity and is used in research for solid tumors. The compound is a research tool for studying BRAF-mutant cancers. |
| Molecular Formula |
C22H21F3N4O4S
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|---|---|
| Molecular Weight |
494.486754179001
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| Exact Mass |
494.123
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| CAS # |
1425485-87-5
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| PubChem CID |
71506198
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
2.8
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
34
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| Complexity |
811
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C(S(NC1=CC(F)=C(F)C(C(C2=CC=C3C(=C2)N=C(N2CCOCC2)C=N3)=O)=C1F)(=O)=O)CC
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| InChi Key |
HAYBWDINAFTFCJ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H21F3N4O4S/c1-2-9-34(31,32)28-17-11-14(23)20(24)19(21(17)25)22(30)13-3-4-15-16(10-13)27-18(12-26-15)29-5-7-33-8-6-29/h3-4,10-12,28H,2,5-9H2,1H3
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| Chemical Name |
N-[2,4,5-trifluoro-3-(3-morpholin-4-ylquinoxaline-6-carbonyl)phenyl]propane-1-sulfonamide
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| Synonyms |
uplarafenib; B-raf-in-10; B-Raf IN 10; 1425485-87-5; uplarafenib [INN];
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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 |
| 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) |
DMSO: 100 mg/mL (202.23 mM)
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| 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 | 2.0223 mL | 10.1114 mL | 20.2229 mL | |
| 5 mM | 0.4045 mL | 2.0223 mL | 4.0446 mL | |
| 10 mM | 0.2022 mL | 1.0111 mL | 2.0223 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.
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