MYC degrader 1 (compound A80.2HCl) is an orally available MYC degrader with antitumor activity. MYC degrader 1 restores pRB1 protein activity and re-establishes sensitivity of MYC over-expressing cancer cells to CDK4/6 inhibitors.
MYC degrader 1 (0-1000 nM; 24 h) degrades MYC in T24, C4-2, MDA-MB-231, 22RV1,T47D and UMUC14 cell lines[1].MYC degrader 1 (10 nM; 24 h) treatment of T24 and UMUC14 cells significantly reduces the IC50 of Palbociclib from 8.37 and 97.39 to 3.11 and 10.23 μM, respectively[1].MYC degrader 1 (10 nM; 24 h) enhances the inhibition of cell cycle genes and colony formation by Palbociclib in drug-resistant cancer cell lines T24, C4-2 MDA-MB-231[1].
MYC degrader 1 (6 mg/kg; p.o.; once daily for 7 days) inhibits the growth of T24 and UMUC14 xenograft tumors in mice, but had little effect on MYC-deficient xenograft tumors[1].MYC degrader 1 (6 mg/kg; i.g.; once daily for 30 days) enhances the inhibitory effect of Palbociclib on tumor growth in T24 xenograft mice[1].
References:
[1]. Ma J, et al. MYC induces CDK4/6 inhibitors resistance by promoting pRB1 degradation. Nat Commun. 2024 Feb 29;15(1):1871.