| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
RAF (BRAF mutants including V600E, V600K, G464V, G469A, K601E)
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|---|---|
| ln Vitro |
PROTAC RAF degrader 1 (compound 512) potently induces targeted degradation of multiple BRAF mutants with DC₅0 values: 5.4 nM (BRAF V600E), 4.64 nM (V600K), 15.5 nM (G464V), 2.11 nM (G469A), and 63.9 nM (K601E). It displays anti‑cancer activity and may be used to study RAF‑driven diseases including cancers.
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| ln Vivo |
No detailed in vivo activity data for PROTAC RAF degrader 1 has been reported. As a potent degrader of multiple BRAF mutants, it is expected to suppress tumor growth in BRAF‑mutant xenograft models with sustained target degradation and reduced paradoxical MAPK activation.
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| Enzyme Assay |
For binding studies, recombinant BRAF mutant proteins are incubated with PROTAC 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 |
PROTAC RAF degrader 1 is dissolved in DMSO and diluted in cell culture media (final DMSO ≤0.1%). BRAF‑mutant melanoma cells (e.g., A375 for V600E, SK-MEL-28 for V600E) are treated with compound at concentrations ranging from 0.1‑1000 nM for 6‑24 h. BRAF and pERK levels are assessed by Western blotting. Cell proliferation is evaluated using MTT or CellTiter-Glo assays after 72‑96 h of treatment.
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| Animal Protocol |
No detailed in vivo protocol for PROTAC 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 BRAF‑mutant melanoma xenografts. Tumor growth inhibition, BRAF degradation, and pERK suppression would be assessed.
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| ADME/Pharmacokinetics |
No PK data for PROTAC RAF degrader 1 has been reported. As a high‑molecular‑weight PROTAC (MW 1010.18), it is likely to have low oral bioavailability and require parenteral administration. Detailed parameters such as half‑life, Cmax, and clearance are not publicly available.
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| Toxicity/Toxicokinetics |
No toxicity data for PROTAC RAF degrader 1 has been reported. As a BRAF mutant degrader, potential toxicities may include skin rash and gastrointestinal effects. The high selectivity for mutant BRAF may reduce paradoxical MAPK activation, potentially improving the safety profile compared to conventional BRAF inhibitors. No toxicology studies have been published.
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| References |
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| Additional Infomation |
PROTAC RAF degrader 1 (compound 512; CAS: 2413035-41-1; formula: C₅1H₅₇F2N₉O₇S2; MW: 1010.18) is a potent PROTAC degrader of multiple BRAF mutants, based on vemurafenib (PLX4032). It displays DC₅0 values in the low nanomolar range for several clinically relevant BRAF mutations. The compound is for research use only; no clinical trials or regulatory approvals have been reported.
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| Molecular Formula |
C51H57F2N9O7S2
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|---|---|
| Molecular Weight |
1010.18119597435
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| Exact Mass |
1009.379
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| CAS # |
2413035-41-1
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| PubChem CID |
146547699
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
6.4
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
15
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| Rotatable Bond Count |
17
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| Heavy Atom Count |
71
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| Complexity |
1940
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| Defined Atom Stereocenter Count |
3
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| SMILES |
S1C=NC(C)=C1C1C=CC(=CC=1)CNC([C@@H]1C[C@H](CN1C([C@H](C(C)(C)C)NC(CN1CCN(C2C=CC(C3C=NC4=C(C(C(C5C(=CC=C(C=5F)NS(CCC)(=O)=O)F)=O)=CN4)C=3)=CC=2)CC1)=O)=O)O)=O
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| InChi Key |
MBCAVOCJJAQHHT-FGUOTCRGSA-N
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| InChi Code |
InChI=1S/C51H57F2N9O7S2/c1-6-21-71(68,69)59-40-16-15-39(52)43(44(40)53)45(65)38-26-55-48-37(38)22-34(25-54-48)32-11-13-35(14-12-32)61-19-17-60(18-20-61)28-42(64)58-47(51(3,4)5)50(67)62-27-36(63)23-41(62)49(66)56-24-31-7-9-33(10-8-31)46-30(2)57-29-70-46/h7-16,22,25-26,29,36,41,47,59,63H,6,17-21,23-24,27-28H2,1-5H3,(H,54,55)(H,56,66)(H,58,64)/t36-,41+,47-/m1/s1
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| Chemical Name |
(2S,4R)-1-[(2S)-2-[[2-[4-[4-[3-[2,6-difluoro-3-(propylsulfonylamino)benzoyl]-1H-pyrrolo[2,3-b]pyridin-5-yl]phenyl]piperazin-1-yl]acetyl]amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide
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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: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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: 160 mg/mL (158.39 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 4 mg/mL (3.96 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 40.0 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: ≥ 4 mg/mL (3.96 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 40.0 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 | 0.9899 mL | 4.9496 mL | 9.8992 mL | |
| 5 mM | 0.1980 mL | 0.9899 mL | 1.9798 mL | |
| 10 mM | 0.0990 mL | 0.4950 mL | 0.9899 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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