PROTAC BRAF-V600E degrader-2
PROTAC BRAF-V600E degrader-2 is a PROTAC degrader targeting BRAF-V600E. The Kd values of PROTAC BRAF-V600E degrader-2 for BRAF and BRAF-V600E are 14.4 nM and 9 nM, respectively. PROTAC BRAF-V600E degrader-2 selectively degrades BRAF-V600E but does not degrade wild-type BRAF. PROTAC BRAF-V600E degrader-2 inhibits the MEK/ERK kinase cascade and suppresses the growth of melanoma cells. PROTAC BRAF-V600E degrader-2 can be used in studies related to melanoma and colon cancer.
(Pink: B-RafV600E ligand (HY-184546); Blue: Cereblon ligand (HY-W087383); Black: linker (HY-W074340)).
For research use only. We do not sell to patients.
- CAS No.: 2417296-82-1
- Formula: C42H39F2N7O8S
- Molecular Weight:839.86
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Biological Activity
Description
IC50 & Target
[1]|
BRAF-V600E 9.5 nM (Kd) |
Braf 14.4 nM (Kd) |
Cereblon |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
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| A-375 | IC50 |
500 nM
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Reduction of cell viability in BRAF-V600E-expressing A375 melanoma cells assessed by cell viability assay.
Reduction of cell viability in BRAF-V600E-expressing A375 melanoma cells assessed by cell viability assay.
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32223235 |
| HT-29 | IC50 |
124 nM
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Reduction of cell viability in BRAF-V600E-expressing HT-29 colon cancer cells assessed by cell viability assay.
Reduction of cell viability in BRAF-V600E-expressing HT-29 colon cancer cells assessed by cell viability assay.
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32223235 |
In Vitro
PROTAC BRAF-V600E degrader-2 (compound 12) (500 nM; 6 h)-mediated degradation of BRAFV600E in A375 melanoma cells is dependent on the cereblon-containing cullin-ubiquitin proteasome system[1].
PROTAC BRAF-V600E degrader-2 (compound 12) impairs cell viability in BRAFV600E-expressing A375 melanoma cells with an IC50 of 500 nM and in HT-29 colon cancer cells with an IC50 of 124 nM[1].
PROTAC BRAF-V600E degrader-2 (compound 12) (40-1000 nM) inhibits colony formation in BRAFV600E-expressing A375 melanoma cells, with significant inhibition at 1000 nM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:A375 melanoma cells (BRAF-V600E-expressing)
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Concentration:1-1000 nM (16 h incubation); 500 nM (kinetic analysis)
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Incubation Time:16 h (1-1000 nM); 2-24 h (500 nM kinetic analysis)
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Result:Induced reduction of BRAF-V600E protein levels starting at 12 nM.
Suppressed downstream ERK phosphorylation corresponding to BRAF-V600E degradation.
Showed a moderate hook effect at 1000 nM.
Detected significant BRAF-V600E depletion after 16 h of incubation with 500 nM.
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Cell Line:A549 lung cancer cells (wild type BRAF-expressing)
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Concentration:1-1000 nM
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Incubation Time:16 h
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Result:Did not result in significant degradation of wild type BRAF protein.
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Cell Line:A375 melanoma cells stably expressing FLAG-tagged BRAF kinase domain (wild type or V600E mutant)
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Concentration:1-1000 nM
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Incubation Time:16 h
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Result:Selectively degraded the FLAG-tagged BRAF-V600E kinase domain.
Did not degrade the FLAG-tagged wild type BRAF kinase domain.
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Cell Line:A375 melanoma cells (BRAF-V600E-expressing)
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Concentration:500 nM (6 h incubation); 10 μM pomalidomide, 20 μM MG-132, 200 nM bortezomib, 1 μM MLN4924 (1 h pretreatment)
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Incubation Time:6 h (500 nM); 1 h (pretreatments)
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Result:Induced degradation of BRAF-V600E was rescued by pretreatment with proteasome inhibitors (MG-132, bortezomib), cereblon competitor pomalidomide, or NEDD8-activating enzyme inhibitor MLN4924.
Chemical Information
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CAS No. 2417296-82-1
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Molecular Weight 839.86
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Formula C42H39F2N7O8S
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SMILES
O=C(NCC1=CC=C(C2=CN=C(NC=C3C(C4=C(F)C=CC(NS(=O)(CCC)=O)=C4F)=O)C3=C2)C=C1)CCCCNC5=CC6=C(C(N(C(CC7)C(NC7=O)=O)C6=O)=O)C=C5
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
PROTAC BRAF-V600E degrader-2 Related Classifications
HY-137488 Related Classifications
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