| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
B-Raf
B-Raf |
|---|---|
| ln Vitro |
PROTAC B-Raf degrader 1 (compound 2) had IC50 values of 2.7 μM, 21.21 μM, 18.70 μM, 41.11 μM, and 22.68 μM against MCF-7, MDA-MB-231, HepG2, LO2, and B16 cells, respectively [1]. By enlisting the ubiquitin-proteasome system, PROTAC B-Raf degrader 1 (5 or 10 μM) can hasten B-Raf degradation and consequently impact the expression of B-Raf downstream protein Mcl-1 [1]. Following a 24-hour incubation period with a 20 μM concentration of PROTAC B-Raf degrader 1, the MCF-7 cells exhibited an apoptotic rate of 76.70% (early apoptosis 64.00%, late apoptosis 12.70%) [1]. The cell cycle is stopped in the G2/M phase by PROTAC B-Raf degrader 1 [1].
PROTAC B-Raf degrader 1 (compound 2) inhibits the growth of breast cancer cell lines, with IC₅0 values of 2.7 uM (MCF-7), 21.21 uM (MDA-MB-231), 18.70 uM, 41.11 uM, and 22.68 uM against other cell lines. It induces B‑Raf degradation via the ubiquitin‑proteasome pathway, leading to reduced Mcl‑1 expression and suppression of MAPK signaling. |
| ln Vivo |
No detailed in vivo activity data for PROTAC B-Raf degrader 1 has been reported. As a B‑Raf degrader, it is expected to inhibit tumor growth in B‑Raf‑dependent cancer xenograft models by inducing sustained B‑Raf degradation and downstream pathway suppression.
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| Enzyme Assay |
For binding studies, recombinant B‑Raf protein is incubated with PROTAC B-Raf degrader 1 (0.1‑1000 nM), and binding affinity is determined by surface plasmon resonance or fluorescence polarization. The mechanism of degradation is confirmed by co‑treatment with proteasome inhibitors (e.g., MG132) in cellular assays.
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| Cell Assay |
Cell Cytotoxicity Assay[1]
Cell Types: Human MCF-7 breast cancer cell line, MDA-MB-231 breast cancer cells, human HepG2 hepatoma cells, human normal LO2 liver cells, B16 cells. Tested Concentrations: 0-200 μM. Incubation Duration: 72 hrs (hours). Experimental Results: The IC50 values are 2.7 μM, 21.21 μM, 18.70 μM, 41.11μM and 22.68 μM in MCF-7, MDA-MB-231, HepG2, LO2 and B16 cells, respectively. Western Blot Analysis[1] Cell Types: Human MCF-7 breast cancer cell line. Tested Concentrations: 5 or 10 μM. Incubation Duration: 24 hrs (hours). Experimental Results: Effectively induced the degradation of B-Raf and impacted the expression of Mcl-1. Apoptosis Analysis[1] Cell Types: Human MCF-7 breast cancer cell line. Tested Concentrations: 2.7-20 μM. Incubation Duration: 24 hrs (hours). Experimental Results: Achieved an apoptosis rate of 76.70% (64.00% early apoptosis, 12.70% late apoptosis) after 24 h incubation with the concentration of 20 μM. Cell Cycle Analysis[1] Cell Types: Human MCF-7 breast cancer cell line. Tested Concentrations: 20 μM. Incubation Duration: 24 hrs (hours). Experimental Results: 1.94% cells wer PROTAC B-Raf degrader 1 is dissolved in DMSO and diluted in cell culture media (final DMSO ≤0.1%). Breast cancer cells (e.g., MCF-7, MDA-MB-231) are treated with compound at concentrations ranging from 0.1‑100 uM for 24‑72 h. B‑Raf and Mcl‑1 levels are assessed by Western blotting. Cell proliferation is evaluated using MTT or CellTiter-Glo assays after 72 h of treatment. |
| Animal Protocol |
No detailed in vivo protocol for PROTAC B-Raf degrader 1 has been reported. Based on standard procedures for PROTACs, the compound would be formulated in a suitable vehicle (e.g., 10% DMSO, 40% PEG400, 5% Tween 80) and administered intraperitoneally to mice bearing breast cancer xenografts. Tumor growth inhibition and B‑Raf degradation would be assessed.
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| ADME/Pharmacokinetics |
No PK data for PROTAC B-Raf degrader 1 has been reported. As a Cereblon‑based PROTAC degrader, it is likely to have moderate oral bioavailability and require optimization for metabolic stability. Detailed parameters such as half‑life, Cmax, and clearance are not publicly available.
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| Toxicity/Toxicokinetics |
No toxicity data for PROTAC B-Raf degrader 1 has been reported. As a B‑Raf degrader, potential toxicities may include skin rash, gastrointestinal effects, and paradoxical activation of the MAPK pathway if selectivity is not maintained. No toxicology studies have been published.
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| References | |
| Additional Infomation |
PROTAC B-Raf degrader 1 (CAS: 2364367-27-9; formula: C3₆H3₇N₅O12S; MW: 763.77) is a Cereblon‑based PROTAC that induces B‑Raf degradation with anti‑cancer activity. It affects the expression of Mcl‑1, a downstream protein of B‑Raf. The compound is for research use only. No clinical trials or regulatory approvals have been reported.
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| Molecular Formula |
C36H37N5O12S
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|---|---|
| Molecular Weight |
763.77
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| Exact Mass |
763.215
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| CAS # |
2364367-27-9
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| PubChem CID |
138319681
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
1136.9±65.0 °C at 760 mmHg
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| Flash Point |
641.4±34.3 °C
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| Vapour Pressure |
0.0±0.3 mmHg at 25°C
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| Index of Refraction |
1.643
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| LogP |
0.91
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
13
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| Rotatable Bond Count |
15
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| Heavy Atom Count |
54
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| Complexity |
1540
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| Defined Atom Stereocenter Count |
0
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| SMILES |
COC1=C(C=C(C=C1)CS(=O)(=O)/C=C/C2=C(C=C(C=C2OC)OC)OC)NCC(=O)NCC(=O)NC3=CC=CC4=C3C(=O)N(C4=O)C5CCC(=O)NC5=O
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| InChi Key |
AMOFJSISJOOLNX-OUKQBFOZSA-N
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| InChi Code |
InChI=1S/C36H37N5O12S/c1-50-21-15-28(52-3)22(29(16-21)53-4)12-13-54(48,49)19-20-8-10-27(51-2)25(14-20)37-17-31(43)38-18-32(44)39-24-7-5-6-23-33(24)36(47)41(35(23)46)26-9-11-30(42)40-34(26)45/h5-8,10,12-16,26,37H,9,11,17-19H2,1-4H3,(H,38,43)(H,39,44)(H,40,42,45)/b13-12+
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| Chemical Name |
N-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]-2-oxoethyl]-2-[2-methoxy-5-[[(E)-2-(2,4,6-trimethoxyphenyl)ethenyl]sulfonylmethyl]anilino]acetamide
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), 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)
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| Solubility (In Vitro) |
DMSO: 25 mg/mL (32.73 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.27 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 (3.27 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 | 1.3093 mL | 6.5465 mL | 13.0929 mL | |
| 5 mM | 0.2619 mL | 1.3093 mL | 2.6186 mL | |
| 10 mM | 0.1309 mL | 0.6546 mL | 1.3093 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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