BJG-05-039 | PAK1 PROTAC | Probechem Biochemicals

Chemical Structure : BJG-05-039

BJG-05-039 (PAK1 PROTAC)

Catalog No.: PC-49535Not For Human Use, Lab Use Only.

BJG-05-039 is a potent, PAK1-selective PROTAC degrader consisting of NVS-PAK1-1 conjugated to lenalidomide, a recruiter of the E3 ubiquitin ligase substrate adaptor Cereblon, shows potent in vitro inhibition of PAK1 (IC50 = 233 nM).

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Biological Activity

BJG-05-039 is a potent, PAK1-selective PROTAC degrader consisting of NVS-PAK1-1 conjugated to lenalidomide, a recruiter of the E3 ubiquitin ligase substrate adaptor Cereblon, shows potent in vitro inhibition of PAK1 (IC50 = 233 nM).

BJG-05-039 displays greater specificity (PAK2 IC50 > 10,000 nM for BJG-05-039 vs. 824 nM for NVS-PAK1-1).

BJG-05-039 (10 nM) induced degradation of PAK1 but not PAK2 in a dose-dependent manner after a 24 hr treatment in breast cancer cell line MCF7 and the ovarian cancer cell line OVCAR3.

BJG-05-039 strongly downregulated the ring-finger protein RNF166 as well as other known IMiD off target proteins, Ikaros (IKZF1) and Aiolos (IKZF3)

Co-treatment of cells with BJG-05-039 and bortezomib, a proteasome inhibitor, prevented PAK1 destabilization, indicating that degradation was dependent on the ubiquitin-proteasome system.

BJG-05-039 reduces levels of phospho-MEK and phospho-ERK, inhibits proliferation in PAK1-dependent, but not PAK2-dependent cell lines (MCF7, IC50=86 nM).

Physicochemical Properties

M.Wt	821.30
Formula	C41H44ClF3N8O5
Appearance	Solid
CAS No.
Storage	Solide Powder -20°C 12 Months; 4°C 6 Months	In Solvent -80°C 6 Months; -20°C 6 Months
Shipping
Solubility	10 mM in DMSO
Chemical Name/SMILES	(3S)-3-((2-chloro-5-(2,2-difluoroethyl)-8-fluoro-5H-dibenzo[b,e][1,4]diazepin-11-yl)amino)-N-(8-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)octyl)pyrrolidine-1-carboxamide

References

1. Hoi-Yee Chow, et al. J Med Chem. 2022 Nov 23. doi: 10.1021/acs.jmedchem.2c00756.