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| Targets |
PROTAC BRAF-V600E degrader-1 targets the BRAF-V600E mutant protein. It is a PROTAC (proteolysis-targeting chimera) that simultaneously binds to the target protein (BRAF-V600E) and an E3 ubiquitin ligase, leading to ubiquitination and proteasomal degradation of the target.
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| ln Vitro |
PROTAC BRAF-V600E degrader-1 (Compound 23)(1 nM-10 μM; 72 hours) decreases the viability of A375 and HT-29 cells [1]. In A375 cells, PROTAC BRAF-V600E degrader-1 (1–1000 nM; 16 hours or 0–24 hours) suppresses the expression of p-ERK and BRAF-V600E [1].
In vitro, PROTAC BRAF-V600E degrader-1 selectively induces degradation of BRAF-V600E but not wild-type BRAF. It inhibits the growth of melanoma cells. It has Kd values of 2 nM for BRAF-V600E and 2.4 nM for B-Raf. |
| ln Vivo |
In vivo, PROTAC BRAF-V600E degrader-1 aims to inhibit cancer cell growth and survival in cancers driven by the BRAF-V600E mutation, particularly melanoma.
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| Enzyme Assay |
In vitro non-cell-based assays for PROTAC BRAF-V600E degrader-1 involve measuring its binding affinity to BRAF-V600E and the E3 ligase. These assays may use surface plasmon resonance (SPR) or other biophysical techniques to determine the Kd values.
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| Cell Assay |
Cell viability assay [1]
Cell Types: A375 and HT-29 Tested Concentrations: 1 nM-10 μM Incubation Duration: 72 h Experimental Results: Inhibited cell viability of A375 and HT-29, IC50 were 46.5 nM and 51 nM respectively. Western Blot Analysis[1] Cell Types: A375 Tested Concentrations: 1, 4, 12, 37, 111, 333 and 1000 nM Incubation Duration: 16 hrs (hours) or 0-24 hrs (hours) Experimental Results: diminished induced ERK phosphorylation. Inhibits p-ERK and BRAF-V600E in a dose- and time-dependent manner. In vitro cell-based assays for PROTAC BRAF-V600E degrader-1 are performed in melanoma cell lines harboring the BRAF-V600E mutation. Cells are treated with the compound, and the levels of BRAF-V600E protein are measured by Western blotting. Cell proliferation and viability are also assessed. |
| Animal Protocol |
In vivo animal experiments with PROTAC BRAF-V600E degrader-1 are conducted in mouse xenograft models of melanoma. The compound is administered, and tumor growth inhibition and BRAF-V600E degradation are assessed.
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| ADME/Pharmacokinetics |
PROTAC BRAF-V600E degrader-1 has a molecular weight of 1001.07 g/mol and the formula C48H54F2N10O10S. It has a purity of >98% and is stored at -20°C.
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| Toxicity/Toxicokinetics |
Specific toxicological data for PROTAC BRAF-V600E degrader-1 are not detailed in the available literature.
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| References | |
| Additional Infomation |
PROTAC BRAF-V600E degrader-1 is a targeted protein degrader that selectively degrades the oncogenic BRAF-V600E mutant. It is a promising therapeutic strategy for cancers driven by this mutation. It is intended for research use.
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| Molecular Formula |
C48H54F2N10O10S
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|---|---|
| Molecular Weight |
1001.0652
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| Exact Mass |
1000.371
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| CAS # |
2417296-84-3
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| PubChem CID |
146161288
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
3.1
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
18
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| Rotatable Bond Count |
22
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| Heavy Atom Count |
71
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| Complexity |
1950
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S(C([H])([H])C([H])([H])C([H])([H])[H])(N([H])C1C([H])=C([H])C(=C(C=1F)N1C([H])=C(C2=C([H])N=C([H])N=C2[H])C2=C1C([H])=C([H])C(=N2)N(C([H])([H])[H])C1([H])C([H])([H])C([H])([H])N(C(C([H])([H])C([H])([H])OC([H])([H])C([H])([H])OC([H])([H])C([H])([H])OC([H])([H])C([H])([H])N([H])C2=C([H])C([H])=C([H])C3C(N(C(C=32)=O)C2([H])C(N([H])C(C([H])([H])C2([H])[H])=O)=O)=O)=O)C([H])([H])C1([H])[H])F)(=O)=O
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| InChi Key |
FMUGAZVOOIUFAT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C48H54F2N10O10S/c1-3-25-71(66,67)56-36-8-7-34(49)45(43(36)50)59-28-33(30-26-51-29-52-27-30)44-37(59)9-11-39(54-44)57(2)31-13-17-58(18-14-31)41(62)15-19-68-21-23-70-24-22-69-20-16-53-35-6-4-5-32-42(35)48(65)60(47(32)64)38-10-12-40(61)55-46(38)63/h4-9,11,26-29,31,38,53,56H,3,10,12-25H2,1-2H3,(H,55,61,63)
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| Chemical Name |
N-[3-[5-[[1-[3-[2-[2-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethoxy]ethoxy]ethoxy]propanoyl]piperidin-4-yl]-methylamino]-3-pyrimidin-5-ylpyrrolo[3,2-b]pyridin-1-yl]-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 : ~170 mg/mL (~169.82 mM)
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| 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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.9989 mL | 4.9947 mL | 9.9893 mL | |
| 5 mM | 0.1998 mL | 0.9989 mL | 1.9979 mL | |
| 10 mM | 0.0999 mL | 0.4995 mL | 0.9989 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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