| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg | |||
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| Other Sizes |
Purity: ≥98%
B-Raf IN 1 is a novel, potent and selective B-Raf inhibitor with IC50 of 24 nM; it is equally potent against c-Raf with IC50 of 25 nM. Moderate selectivity was observed for compound 10n versus p38a (IC50: 0.216 lM) and CAMKII (IC50: 0.822 lM), while high selectivity was observed versus CDK2, CDK4, PKCa, IKKb, JNK1, MK2, PKA, Src, MKK6, PLK1, p70S6K, PI3 Ka, and PDK1 (IC50s: >2 lM). It binds to B-Raf kinase without forming a hinge-binding hydrogen bond. With basic amine residues appended to C-3 aryl residues, cellular activity and solubility were enhanced over previously described compounds of this class.
| Targets |
B-Raf IN 1 (compound 10n) targets Proto-Oncogene Proteins B-raf (B-Raf kinase) [1]
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| ln Vitro |
WM 266-4 and HT29 cells are inhibited by B-Raf IN 1 (Compound 10n) at IC50s of 0.92 and 0.78 μM, respectively[1].
1. B-Raf IN 1 (compound 10n), a C-3 substituted N-(3-(pyrazolo[1,5-a]pyrimidin-7-yl)phenyl)-3-(trifluoromethyl)benzamide, was identified as a potent B-Raf kinase inhibitor [1] 2. X-ray crystallography analysis demonstrated that B-Raf IN 1 bound to B-Raf kinase without forming a hinge-binding hydrogen bond, which is a distinct binding mode compared with conventional B-Raf kinase inhibitors [1] 3. The introduction of basic amine residues to the C-3 aryl residues of pyrazolo[1,5-a]pyrimidines (the structural class of B-Raf IN 1) enhanced cellular activity and solubility relative to previously reported compounds of the same class [1] |
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| ln Vivo |
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| Enzyme Assay |
1. X-ray crystallography assay for B-Raf kinase binding mode: The binding interaction between B-Raf IN 1 and B-Raf kinase was characterized using X-ray crystallography. The experiment was designed to determine the structural basis of the inhibitor's binding to the kinase, focusing on whether hydrogen bonds were formed at the hinge region of B-Raf kinase. The results confirmed that B-Raf IN 1 bound to B-Raf kinase without forming a hinge-binding hydrogen bond [1]
2. Structure-activity relationship (SAR) assay for pyrazolo[1,5-a]pyrimidines: A series of C-3 substituted N-(3-(pyrazolo[1,5-a]pyrimidin-7-yl)phenyl)-3-(trifluoromethyl)benzamides (including B-Raf IN 1) were synthesized and evaluated for their B-Raf kinase inhibitory activity. The impact of structural modifications (e.g., appending basic amine residues to C-3 aryl residues) on the potency, cellular activity and solubility of the compounds was analyzed [1] |
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| Additional Infomation |
1. B-Raf IN 1 belongs to a series of C-3 substituted N-(3-(pyrazolo[1,5-a]pyrimidin-7-yl)phenyl)-3-(trifluoromethyl)benzamide compounds, which are designed as B-Raf kinase inhibitors [1]. 2. B-Raf IN 1's non-hinge binding mode with B-Raf kinase is a key structural feature that distinguishes it from traditional B-Raf kinase inhibitors [1]. 3. By adding a basic amine residue to the aryl residue at the C-3 position, the structure of pyrazolo[1,5-a]pyrimidinyl compounds (including B-Raf IN 1) can be optimized to overcome the limitations of early compounds in this class (e.g., low cellular activity and poor solubility) [1].
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| Molecular Formula |
C29H24F3N5O
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| Molecular Weight |
515.53
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| Exact Mass |
515.193
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| CAS # |
950736-05-7
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| Related CAS # |
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| PubChem CID |
24884503
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Index of Refraction |
1.621
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| LogP |
4.39
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
38
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| Complexity |
787
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
AIWJVLQNYNCDSL-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C29H24F3N5O/c1-36(2)18-19-9-11-20(12-10-19)25-17-34-37-26(13-14-33-27(25)37)21-5-4-8-24(16-21)35-28(38)22-6-3-7-23(15-22)29(30,31)32/h3-17H,18H2,1-2H3,(H,35,38)
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| Chemical Name |
N-[3-[3-[4-[(dimethylamino)methyl]phenyl]pyrazolo[1,5-a]pyrimidin-7-yl]phenyl]-3-(trifluoromethyl)benzamide
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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: ≥ 3.25 mg/mL (6.30 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 32.5 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 + to the above solution and mix evenly; then add 450 μL of 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9398 mL | 9.6988 mL | 19.3975 mL | |
| 5 mM | 0.3880 mL | 1.9398 mL | 3.8795 mL | |
| 10 mM | 0.1940 mL | 0.9699 mL | 1.9398 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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