| Size | Price | |
|---|---|---|
| 500mg | ||
| Other Sizes |
| Targets |
B-Raf V600E mutant kinase (also referred to as BRAF V600E). The compound selectively inhibits the DFG-in conformation of the B-Raf kinase V600E mutant, which is distinct from the DFG-out conformation targeted by some other inhibitors. This target is a key component of the MAPK/ERK signaling pathway that regulates cell proliferation and survival.
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|---|---|
| ln Vitro |
ZINC72115182 demonstrates potent inhibitory activity against B-Raf V600E with an IC50 of 76 nM. It displays approximately 3.1-fold selectivity for the V600E mutant over wild-type B-Raf (IC50 = 238 nM), indicating a favorable selectivity profile. This selective inhibition allows for the specific targeting of mutant B-Raf-driven signaling while sparing wild-type B-Raf activity, which is important for reducing off-target effects in cancer research applications.
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| ln Vivo |
In vivo activity data for ZINC72115182 are limited in the available literature. However, as a selective B-Raf V600E inhibitor, it is expected to exhibit antitumor efficacy in preclinical models of colorectal cancer and other B-Raf mutant-driven tumors. The compound is structurally related to other B-Raf inhibitors that have demonstrated tumor growth inhibition in xenograft models. Further studies are needed to fully characterize its pharmacokinetic and pharmacodynamic profiles in animal models.
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| Enzyme Assay |
The in vitro enzyme inhibition assay for ZINC72115182 typically involves measuring the kinase activity of recombinant B-Raf V600E and wild-type B-Raf proteins using a standardized kinase assay format. The compound is incubated with the enzyme and a peptide substrate in the presence of ATP, and the phosphorylation level is quantified to determine the IC50 value. Selectivity is assessed by comparing the IC50 values against the mutant and wild-type enzymes. The assay is performed in a cell-free system using purified enzyme preparations.
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| Cell Assay |
The in vitro cellular assay for ZINC72115182 typically involves culturing B-Raf V600E mutant colorectal cancer cell lines (such as HT-29 or Colo-205) in appropriate growth media. Cells are treated with varying concentrations of the compound for a specified duration (typically 48-72 hours), and cell viability is assessed using standard assays such as MTT or CellTiter-Glo. The antiproliferative effect is quantified by determining the half-maximal inhibitory concentration (IC50) in the cellular context.
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| Animal Protocol |
In vivo animal studies for ZINC72115182 would typically involve the use of mouse xenograft models bearing B-Raf V600E mutant human colorectal tumors. Tumor-bearing mice are administered the compound via oral gavage or intraperitoneal injection at various dose levels, and tumor growth inhibition is monitored over several weeks. Endpoints include tumor volume measurements, body weight changes, and histopathological analysis of tumor tissues to assess the antitumor efficacy and potential toxicity.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic properties of ZINC72115182 are not extensively reported in the available literature. As a small molecule with a molecular weight of 458.28 g/mol, it is expected to have moderate oral bioavailability and tissue penetration. The compound shows good solubility in DMSO (100 mg/mL), suggesting reasonable physicochemical properties for in vivo studies. Further PK studies are needed to determine parameters such as half-life, clearance, and volume of distribution.
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| Toxicity/Toxicokinetics |
Specific toxicology data for ZINC72115182 are not available in the public domain. However, as with all B-Raf inhibitors, potential toxicities may include skin reactions, gastrointestinal disturbances, and other off-target effects associated with MAPK pathway inhibition. The compound is intended for research use only and should be handled with appropriate laboratory safety precautions. Comprehensive toxicity studies would be required before any clinical application.
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| References | |
| Additional Infomation |
ZINC72115182 is also known as B-Raf IN 11 and is commercially available as a research chemical. It functions as a Type II inhibitor that binds to the DFG-in conformation of the B-Raf kinase domain. The compound is primarily used in the study of colorectal cancer and other malignancies harboring the B-Raf V600E mutation. It has not yet entered clinical trials and is strictly for preclinical research purposes. The molecular formula is C17H14BrF2N3O3S with a purity of >98%.
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| Molecular Formula |
C17H14BRF2N3O3S
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|---|---|
| Molecular Weight |
458.2772
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| Exact Mass |
456.991
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| CAS # |
918504-27-5
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| PubChem CID |
11984556
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| Appearance |
Off-white to light yellow solid powder
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| Boiling Point |
634.2°C
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| LogP |
5.14
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
27
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| Complexity |
648
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
TVFGCDQPUZGXMQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H14BrF2N3O3S/c1-2-5-27(25,26)23-13-4-3-12(19)14(15(13)20)16(24)11-8-22-17-10(11)6-9(18)7-21-17/h3-4,6-8,23H,2,5H2,1H3,(H,21,22)
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| Chemical Name |
N-[3-(5-bromo-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluorophenyl]propane-1-sulfonamide
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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 (~218.21 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.46 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 25.0 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: ≥ 2.5 mg/mL (5.46 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1821 mL | 10.9104 mL | 21.8207 mL | |
| 5 mM | 0.4364 mL | 2.1821 mL | 4.3641 mL | |
| 10 mM | 0.2182 mL | 1.0910 mL | 2.1821 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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