DRAK Inhibitor

GW296115 is a multi-target inhibitor with the following IC₅₀ values against its targets: 8.4 nM for BRSK2, 21 nM for BRSK1, 1.8 μM for PDGFRβ, 5.5 nM for STK17B/DRAK2, 28 nM for DRAK1, 20 nM for PHKG1, and 89 nM for DCAMKL3. GW296115 downregulates the phosphorylation of S317 site on ULK1 and S351 site on P62, which are AMPK substrates driven by BRSK2. GW296115 does not alter the phosphorylation level of AMPK at T172, reduces nutrient deprivation-mediated Autophagy and autophagosome formation, and enhances Apoptosis. GW296115 exhibits anticancer activity against triple-negative breast cancer. GW296115 is applicable for breast cancer-related research.

DRAK2-IN-2 is a selective DRAK2 inhibitor with an IC₅₀ value of 198.5 nM. DRAK2-IN-2 inhibits DRAK2-mediated phosphorylation of ULK1 at the Ser56 site. DRAK2-IN-2 enhances insulin secretion, increases mitochondrial membrane potential, alleviates Palmitic acid (HY-N0830)-induced mitochondrial membrane potential damage and Apoptosis, and improves glucose tolerance in vivo. DRAK2-IN-2 can be used for the research of type 2 diabetes.