| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| Other Sizes |
| Targets |
BRAF-V600E 9.5 nM (Kd) Braf 14.4 nM (Kd) Cereblon
BRAF, BRAF-V600E |
|---|---|
| ln Vitro |
PROTAC BRAF-V600E degrader-2 (compound 12) shows binding affinities (Kd) of 14.4 nM for BRAF and 9.5 nM for the BRAF-V600E mutant. It selectively degrades the kinase domain of BRAF-V600E but does not degrade wild‑type BRAF, demonstrating excellent selectivity. The compound inhibits the growth of melanoma cells that harbor the BRAF‑V600E mutation.
|
| ln Vivo |
No detailed in vivo activity data has been reported for PROTAC BRAF-V600E degrader-2. As a selective BRAF-V600E degrader, it is expected to suppress tumor growth in BRAF‑mutant melanoma xenograft models with reduced potential for paradoxical activation of the MAPK pathway compared to traditional BRAF inhibitors.
|
| Enzyme Assay |
For binding affinity determination, recombinant BRAF and BRAF-V600E proteins are incubated with various concentrations of PROTAC BRAF-V600E degrader-2 (0.1‑1000 nM). Kd values are determined using surface plasmon resonance (SPR) or fluorescence polarization‑based competition binding assays.
|
| Cell Assay |
PROTAC BRAF-V600E degrader-2 is dissolved in DMSO and diluted in cell culture media (final DMSO ≤0.1%). BRAF‑V600E mutant melanoma cells (e.g., A375, SK-MEL-28) are treated with the compound at concentrations ranging from 1 nM to 10 uM for 6‑24 h. BRAF and phospho‑ERK levels are assessed by Western blotting. Cell proliferation is evaluated using MTT or CellTiter-Glo assays.
|
| Animal Protocol |
No detailed in vivo protocol for PROTAC BRAF-V600E degrader-2 has been reported. Based on standard procedures for BRAF-targeting PROTACs, the compound would be formulated in a suitable vehicle (e.g., 10% DMSO, 40% PEG400, 5% Tween 80) and administered intraperitoneally or orally to mice bearing BRAF‑V600E melanoma xenografts. Tumor growth and degradation of BRAF-V600E would be assessed.
|
| ADME/Pharmacokinetics |
No PK data for PROTAC BRAF-V600E degrader-2 has been reported. As a 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.
|
| Toxicity/Toxicokinetics |
No toxicity data for PROTAC BRAF-V600E degrader-2 has been reported. As a selective degrader of mutant BRAF, potential toxicities may include skin rash, gastrointestinal effects, and paradoxical activation of the MAPK pathway in wild‑type BRAF cells if selectivity is lost at high doses. No toxicology studies have been published.
|
| References | |
| Additional Infomation |
PROTAC BRAF-V600E degrader-2 (compound 12; CAS: 2417296-82-1; formula: C42H3₉F2N₇O₈S; MW: 839.86) is a highly selective, potent PROTAC degrader of BRAF-V600E for research use only. It selectively degrades the mutant protein without affecting wild‑type BRAF, potentially offering a safer therapeutic window compared to non‑selective BRAF inhibitors. No clinical trials or regulatory approvals have been reported.
|
| Exact Mass |
839.255
|
|---|---|
| CAS # |
2417296-82-1
|
| PubChem CID |
155551346
|
| Appearance |
Typically exists as solid at room temperature
|
| Hydrogen Bond Donor Count |
5
|
| Hydrogen Bond Acceptor Count |
13
|
| Rotatable Bond Count |
16
|
| Heavy Atom Count |
60
|
| Complexity |
1730
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CCCS(=O)(=O)NC1=C(C(=C(C=C1)F)C(=O)C2=CNC3=C2C=C(C=N3)C4=CC=C(C=C4)CNC(=O)CCCCNC5=CC6=C(C=C5)C(=O)N(C6=O)C7CCC(=O)NC7=O)F
|
| InChi Key |
AAIPPJPUZKZIHC-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C42H39F2N7O8S/c1-2-17-60(58,59)50-32-13-12-31(43)36(37(32)44)38(54)30-22-48-39-28(30)18-25(21-47-39)24-8-6-23(7-9-24)20-46-34(52)5-3-4-16-45-26-10-11-27-29(19-26)42(57)51(41(27)56)33-14-15-35(53)49-40(33)55/h6-13,18-19,21-22,33,45,50H,2-5,14-17,20H2,1H3,(H,46,52)(H,47,48)(H,49,53,55)
|
| Chemical Name |
N-[[4-[3-[2,6-difluoro-3-(propylsulfonylamino)benzoyl]-1H-pyrrolo[2,3-b]pyridin-5-yl]phenyl]methyl]-5-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]amino]pentanamide
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| 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.) |
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.
Products are for research use only; We do not sell to patients
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