tcsc0042190 AZD-0364

AZD-0364 is a potent and selective ERK2 inhibitor extracted from patent WO2017080979A1, compound example 18, has an IC₅₀ of 0.6 nM.

IC50 & Target: IC50: 0.6 nM (ERK2)^[1]

In Vitro: AZD-0364 is measured in the ERK2 mass spectrometry and A375 phospho-p90RSK assays with IC₅₀s of 0.6 nM and 5.7 nM, respectively. AZD-0364 can inhibit the growth of a panel of cancer cell lines (A549, H2122, H2009, and Calu6 cell lines) with KRAS mutations as a monotherapy and this effect is synergistically enhanced by treatment with Selumetinib^[1].

In Vivo: Tumor growth inhibition by AZD-0364 ethanesulfonic acid (Example 18a) in combination with MEK inhibitor Selumetinib is measured. Studies are performed in the A549 xenograft model. Selumetinib is dosed twice daily (BiD) 8 hours apart and AZD-0364 ethanesulfonic acid is dosed once daily (QD) 4 hours after the first Selumetinib dose. Both compounds are dosed continuously for 3 weeks. Both vehicles are dosed in the vehicle group. Both Selumetinib and AZD-0364 ethanesulfonic acid reduce tumor growth relative to vehicle only control. The combination of Selumetinib and AZD-0364 ethanesulfonic acid results in a reduction in tumor growth^[1].