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P4B | P4B : Degrader (PROTAC) of BRAF
RATINGS:
Cellular Use: (3 reviews)

In Model Organisms: (0 reviews)
Probe Summary
Selectivity
Potency
In Vivo
Control Compounds
Chemical Information
References
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Probe Summary

Targets Biochemical/Biophysical Potency Cellular Potency
BRAF (Mutant:V600E)
  • IC50:2570 nM
  • IC50:33 nM
  • Kd:4.7 nM
  • Kd:5.6 nM
  • DC50:15 nM
  • Dmax:82%
  • IC50:8 - 71 nM
  • IC50:71 nM
Degrader (PROTAC)
up to 500 nM

Selectivity

In Cell Selectivity Assessment
Potency Assay Off-Target:
V600E specific mutant, tested against WT and other mutants in pERK and proliferation assays. Weaker ...
In Cell Selectivity Assessment
Potency Assay Off-Target:
Kinome wide profiling, displacing with the broad-spectrum protein kinase inhibitor CTx-0294885 coval ...
In Cell Selectivity Assessment
Potency Assay Off-Target:
Proteome-wide analysis of protein levels after 24 h of P4B treatment revealed that of 7,200 detectab ...

Potency
Cellular
In Vitro

BRAF (Mutant:V600E)

Mode of Action: Degrader (PROTAC)

Structure-Activity-Relationship data available? No

DOI Reference: 10.1038/s41589-020-0609-7

Negative Control Compounds

canSAR3135622
Notes: P4D-Me (cpd 20) is the methylated version of E3 binding warhead and is not able to degrade the target in several cells types. Inhibitory activity of P4D-Me is reduced by 10/20 fold compare to P4D

Orthogonal Probes def

DABRAFENIB

Chemical Information

Molecular Formula C50H58F2N10O11S
SMILEs CCCS(=O)(=O)Nc1ccc(F)c(-n2cc(-c3cncnc3)c3nc(N(C)C4CCN(C(=O)CCOCCOCCOCCOCCNc5cccc6c5C(=O)N(C5CCC(=O)NC5=O)C6=O)CC4)ccc32)c1F
InChI InChI=1S/C50H58F2N10O11S/c1-3-27-74(68,69)58-38-8-7-36(51)47(45(38)52)61-30-35(32-28-53-31-54-29-32)46-39(61)9-11-41(56-46)59(2)33-13-17-60(18-14-33)43(64)15-19-70-21-23-72-25-26-73-24-22-71-20-16-55-37-6-4-5-34-44(37)50(67)62(49(34)66)40-10-12-42(63)57-48(40)65/h4-9,11,28-31,33,40,55,58H,3,10,12-27H2,1-2H3,(H,57,63,65)
Molecular weight 1044.40 Da
AlogP 0.0
HBond acceptors 21
HBond donors 3
Atoms 132

References

Publications

Cross References

canSAR

Expert Reviews

by SERP
(on 26 Jan 2025 )
Cellular Use Rating
The chemical probe is a PROTAC (PROteolysis Targeting Chimera) targeting BRAF. In addition to its key role in MAPK signalling and as a drug target, BRAF has interesting scaffolding functions. Therefore,...
by SERP
(on 28 Jan 2025 )
Cellular Use Rating
( The reviewer did not leave any comments )
by SERP
(on 20 Feb 2025 )
Cellular Use Rating
This is a compound I recommend as chemical probe. Degradation of BRAF was not complete at an early time point, but reached it's maximum over ~41 h .
Note: The Chemical Probes Portal only endorses compounds as chemical probes for use as specific and selective modulators of the proposed target if they receive three or more (3-4) stars. Read more about our evaluation criteria