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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

P4D-Me
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

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 public 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