Uses
IC 86621 is a potent DNA-dependent protein kinase (DNA-PK) inhibitor, with an IC50 of 120 nM. IC 86621 also acts as a selective and reversible ATP-competitive inhibitor.IC 86621 inhibits DNA-PK mediated cellular DNA double-strand break (DSB) repair (EC50=68 μM). IC 86621 increases DSB-induced antitumor activity without cytotoxic effects. IC 86621 can protects rheumatoid arthritis (RA) T cells from apoptosis[1][2].
General Description
A cell-permeable aryl-morpholino compound that acts as a potent, selective, reversible, and ATP-competitive inhibitor of DNA-PK (IC
50 = 120 nM) and PI 3-Kinase catalytic subunit p110β (IC
50 = 135 nM). It inhibits DNA-PK-mediated cellular DNA DSB (double strand break) repair (EC
50 = 68 μM) and enhances DSB-induced antitumor activity both
in vitro and
in vivo, while exhibiting no cytotoxic effects (up to 50 μM) in the absence of DSBs. It inhibits PI 3-K p110α, p110γ, and p110δ only at much higher concentrations (IC
50 = 1.4, 0.88, and 1.0 μM, respectively) and exhibits no effect against a panel of several other kinases, including, Cdk2, Src, PKA, PKC, Chk1, CK1, ATM, and FKBP12, even at concentrations as high as 100 μM.
References
[1] Chandra G, et al. Improved synthesis of a DNA-dependent protein kinase inhibitor IC86621. Arch Pharm Res. 2012 Mar;35(4):639-45. DOI:
10.1007/s12272-012-0407-1[2] Shao L, et al. DNA-dependent protein kinase catalytic subunit mediates T-cell loss in rheumatoid arthritis. EMBO Mol Med. 2010 Oct;2(10):415-27. DOI:
10.1002/emmm.201000096
