A2AAR/HDAC-IN-1

A2AAR/HDAC-IN-1 (compound 14c) is an orally active, potent and balanced A2AAR/HDAC dual inhibitor, with a Ki of 163.5 nM for A2AAR and an IC50 of 145.3 nM for HDAC1. A2AAR/HDAC-IN-1 shows anticancer activity[1].

Research Areas >> Cancer

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

Signaling Pathways >> Epigenetics >> HDAC

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

A2AR:163.5 ± 14 nM (Ki)

A1AR:503.3 ± 14 nM (Ki)

hA2B:>10000 nM (Ki)

Adenosine A3 receptor:>10000 nM (Ki)

HDAC1:145.3 ± 12 nM (IC50)

HDAC2:240.2 ± 19 nM (IC50)

HDAC3:443.5 ± 27 nM (IC50)

HDAC6:>10000 nM (IC50)

HDAC8:>10000 nM (IC50)

A2AAR/HDAC-IN-1 (compound 14c) (0-100 μM, 72 h) shows anti-proliferative activities against colon cancer cell lines, CT26 and MC38[1]. A2AAR/HDAC-IN-1 (0-5 μM, 24 h) increases histone acetylation[1]. A2AAR/HDAC-IN-1 shows moderate selectivity against A1AR (3-fold) and no significant binding for A2BAR and A3AR[1]. Cell Proliferation Assay[1] Cell Line: Colon cancer cell lines (CT26 and MC38) Concentration: 0-100 μM Incubation Time: 72 h Result: Displayed good cytotoxicity in CT26 and MC38 cells, with GI50 values of 0.29 ± 0.03 μM and 0.38 ± 0.03 μM, respectively. Western Blot Analysis[1] Cell Line: MC38 mouse colon cancer cells Concentration: 0, 0.1, 1, and 5 μM Incubation Time: 24 h Result: Increased histone H3 and H4 acetylation 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.