A2AAR/HDAC-IN-2

A2AAR/HDAC-IN-2 is a potent A2AAR/HDAC dual inhibitor, with good binding affinity for A2AAR (Ki=10.3 nM) and good inhibitory activity against HDAC1 (IC50=18.5 nM). A2AAR/HDAC-IN-2 can be used in study of antitumor[1].

Research Areas >> Cancer

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

Signaling Pathways >> Epigenetics >> HDAC

Signaling Pathways >> GPCR/G Protein >> Adenosine Receptor

HDAC1:18.5 nM (IC50)

HDAC2:16.0 nM (IC50)

HDAC3:13.6 nM (IC50)

HDAC6:2.1 nM (IC50)

HDAC8:1408.9 nM (IC50)

A1AR:105.6 nM (Ki)

A2AAR:10.3 nM (Ki)

A2BAR:513.0 nM (Ki)

A3AR:＞10 μM (IC50)

A2AAR/HDAC-IN-2 (compound 30c) (5 nM-100 µM; 72 h) shows anti-proliferative activity, with GI50s of 12.16 and 12.61 µM for CT26 and MC38 cells, respectively[1]. A2AAR/HDAC-IN-2 (0.1, 1, 5, 10 µM; 24 h) increases histone H3 and H4 acetylation in a concentration-dependent manner in MC38 cells[1]. Cell Proliferation Assay[1] Cell Line: MC38 and CT26 cells Concentration: 5 nM-100 µM Incubation Time: 72 h Result: Showed good anti-proliferative activity in cancer cell lines, with GI50s of 12.16 and 12.61 µM for CT26 and MC38 cells, respectively. Western Blot Analysis[1] Cell Line: MC38 cells Concentration: 0.1, 1, 5, 10 µM Incubation Time: 24 h Result: Significantly increases histone H3 and H4 acetylation at 10 µM and in a concentration-dependent manner.

[1]. Zhang J, et al. Dual-acting antitumor agents targeting the A2A adenosine receptor and histone deacetylases: Design and synthesis of 4-(furan-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine derivatives. Eur J Med Chem. 2022 Jun 5;236:114326.