Pomalidomide-C3-adavosertib

Pomalidomide-C3-adavosertib is a rapid and selective Wee1 degrader (IC50=3.58 nM). Pomalidomide-C3-adavosertib shows anti-cancer cell proliferation activity, and induces apoptosis[1].

Research Areas >> Cancer

Signaling Pathways >> Cell Cycle/DNA Damage >> Wee1

Pomalidomide-C3-adavosertib (1 nM-10 μM; 24, 48, and 72 h) induces CRBN-dependent anti-proliferative effects and synergized with Olaparib[1]. Pomalidomide-C3-adavosertib (100 nM; 24 h) induces DNA damage, apoptosis, and deregulation of the G2/M checkpoint[1]. Pomalidomide-C3-adavosertib (1 nM-10 μM; 6 h) degrades Wee1 in MOLT4 cells[1]. Cell Proliferation Assay[1] Cell Line: OVCAR8, COV362, and Kuramochi cells Concentration: 1 nM-10 μM Incubation Time: 24, 48, and 72 hours Result: Degraded Wee1 in OVCAR8 cells, with maximal degradation observed at a 100 nM treatment. Cell Cycle Analysis[1] Cell Line: MOLT4 cells Concentration: 100 nM Incubation Time: 24 hours Result: Led to reduced pCDKl Y15, increased apoptosis, and increased unrepaired DNA. Western Blot Analysis[1] Cell Line: MOLT4 cells Concentration: 1 nM-10 μM Incubation Time: 6 hours Result: Degraded Wee1 after a 6-hour treatment in MOLT4 cells, and induced the downstream changes expected from Wee1 loss-including a decrease in phosphorylated cyclin-dependent kinase 1 (pCDK1) and an increase in pH 3.

[1]. Nathanael S. Gray, et al. Degraders of wee1 kinase. WO2020069105A1.