NI-42

Protein target name: 
BRPF1, BRD1, BRPF3
Mechanism of action: 
Inhibitor

Primary Reference

Probe Availability

SAB Comments

The chemical probe NI-57, which is closely related to NI-42, inhibits BRPF1, BRD1, BRPF3 and is the preferred probe for these targets. Although NI-57 is not yet published, it is commercially available. Details for NI-57 are available on the SGC website http://www.thesgc.org/chemical-probes/NI-57.

NI-42 is a moderately potent BRPF1 inhibitor (exact potency unclear as it is assay format dependent, but presuming ITC is preferred format, KD ~40 nM) with moderate selectivity: ~6X selectivity over BRPF2, ~10X over BRD7, ~20-40X selectivity over BRPF3 and BRD9, and much greater selectivity over remaining BRD-containing proteins screened. GSK6853 (http://pubs.acs.org/doi/full/10.1021/acsmedchemlett.6b00092) would appear to be the preferred probe for cellular use, as it is more potent and selective. NI-42 may be the best in vivo tool available for models that require chronic dosing, however, as its pharmacokinetics was compatible with oral dosing, unlike GSK6853 (limited to IP dosing).