Compound 23

PROTAC BRAF-V600E degrader-1 is a potent PROTAC BRAF-V600E degrader with Kd value of 2.4 nM and 2 nM for BRAF and BRAF-V600E, respectively. PROTAC BRAF-V600E degrader-1 degrades BRAF-V600E via the ubiquitin-proteasome system (UPS). PROTAC BRAF-V600E degrader-1 can inhibit melanoma cell growth[1].

Research Areas >> Cancer

Signaling Pathways >> MAPK/ERK Pathway >> Raf

Signaling Pathways >> PROTAC >> PROTAC

BRAF-V600E:2 nM (Kd)

Braf:2.4 nM (Kd)

PROTAC BRAF-V600E degrader-1 (compound 23) (1 nM-10 μM; 72 h) inhibits the cell viability of A375 and HT-29[1]. PROTAC BRAF-V600E degrader-1 (1-1000 nM; 16 h or 0-24 h) inhibits p-ERK and BRAF-V600E protein in A375 cells[1]. Cell Viability Assay[1] Cell Line: A375 and HT-29 Concentration: 1 nM-10 μM Incubation Time: 72 h Result: Inhibited the cell viability of A375 and HT-29 with IC50s of 46.5 nM and 51 nM. Western Blot Analysis[1] Cell Line: A375 Concentration: 1, 4, 12, 37, 111, 333 and 1000 nM Incubation Time: 16 h or 0-24 h Result: Induced the reduction in the phosphorylation of ERK. Inhibited p-ERK and BRAF-V600E in a dose- and time-dependent manner.

[1]. Han XR, et al. Discovery of Selective Small Molecule Degraders of BRAF-V600E. J Med Chem. 2020 Apr 23;63(8):4069-4080.