pi3k/hdac in 1

PI3K/HDAC-IN-1 is a potent dual inhibitor of PI3K and HDAC, with IC50 values of 8.1 nM and 1.4 nM, respectively.

PI3Kδ/HDAC6-IN-1 (Compound 22E) is an orally active dual inhibitor of PI3Kδ and HDAC6, with IC50 values of 2.4 nM and 6.2 nM, respectively. It exhibits potent antiproliferative effects against non-Hodgkin's lymphoma (NHL) cells and demonstrates antitumor activity in vivo without significant toxicity. PI3Kδ/HDAC6-IN-1 induces cell cycle arrest at the G0/G1 phase and triggers apoptosis. Additionally, it inhibits the PI3K/AKT/mTOR signaling pathway and enhances the acetylation levels of α-tubulin and histone H3.

PI3Kα/HDAC6-IN-1 (compound 21j) is a dual inhibitor of PI3Kα and HDAC6, with IC50 values of 2.9 nM and 26 nM, respectively. It hinders AKT(Ser473) phosphorylation and promotes the accumulation of acetylated α-tubulin without affecting acetylated histones H3 and H4. The compound exhibits potent anti-cancer efficacy, inhibiting the L-363 cell line with an IC50 of 0.17 μM [1].

PI3K/HDAC-IN-4 (Compound 31f) is a dual inhibitor targeting PI3K and HDAC, with an IC50 of 0.2μM. It demonstrates high selectivity for HDAC1-3, with IC50 values of 75.5 nM, 70.9 nM, and 1.9 nM, respectively. As a potent pan-PI3K inhibitor, PI3K/HDAC-IN-4 has IC50 values of 2.5 nM, 80.5 nM, 10.0 nM, and 57.2 nM for PI3Kα, β, δ, and γ, respectively. This compound effectively induces apoptosis in tumor cells by concurrently inhibiting the PI3K/AKT/mTOR signaling pathway and HDAC1-3. It shows significant antiproliferative activity across various tumor cell lines, such as MV4-11, Jeko-1, HL60, and MCF-7, with IC50 values of 0.2, 0.9, 0.8, and 1.5 μM, respectively. PI3K/HDAC-IN-4 is applicable in the study of lymphoma and leukemia.

HDAC-IN-43 is a potent HDAC 1/3/6 inhibitor with IC50 values of 82 nM for HDAC 1, 45 nM for HDAC 3, and 24 nM for HDAC 6, and a weak PI3K/mTOR inhibitor with IC50 values of 3.6 μM for PI3K and 3.7 μM for mTOR, exhibiting a broad-spectrum anti-proliferative effect.

PH14, a dual PI3K/HDAC inhibitor, demonstrates potent inhibition with IC50 values of 20.3 nM for PI3Kα and 24.5 nM for HDAC3. It exhibits antiproliferative effects and induces apoptosis in Jeko-1 cells, making it a valuable tool in cancer research, including lymphoma studies [1].

PI3K/HDAC-IN-3 (36) acts as a dual inhibitor targeting PI3K and HDAC, exhibiting respective IC50 concentrations of 0.23 nM for PI3Kα and 172 nM for HDAC1. In MV4-11 cells, it inhibits AKT phosphorylation while enhancing H3 acetylation. Furthermore, PI3K/HDAC-IN-3 (36) demonstrates substantial, dose-dependent anticancer effects in an MV4-11 xenograft model [1].