The novel synthesized PIP-A and PIP-B are potent and specific gene-silencing agents for AURKA and AURKB.
Using synthetic peptides mimicking the FxxF motif present at most C-termini of AGC kinases, we have raised highly specific antibodies which are potent and specific inhibitors of the catalytic activity of the cognate protein kinase.
Paxilline, penitrem A, iberiotoxin, and low concentrations of tetraethyl ammonium are potent and specific inhibitors of BK [16].
They are potent and specific antagonists of several integrins, such as αvβ3 and α5β1, and can thus act on many biological processes including platelet aggregation, angiogenesis, tumor invasion and bone destruction [12], [13], [14], [15].
Unfortunately, none of the BH3 mimetics under current development are potent and specific Mcl-1 antagonists [ 29].
Indeed, they are potent and specific antagonists of several integrins, such as αv β3 and α5 β1 [ 43, 44] and can thus act in many biological processes including platelet aggregation, angiogenesis, tumor invasion, and bone destruction [ 39, 45– 45].
We have recently screened a 5000-strong compound library using human NAT1, human NAT2, mouse Nat1 and mouse Nat2; from these studies, several compounds been have identified which are potent and specific inhibitors of human NAT1 and its mouse homologue, Nat2.
Our novel compounds 3 and 4 are potent and specific Sirt2 inhibitors in vitro, and we next tested the effect of 4 (compound 3 is likely to be sensitive to esterase activity in lysates) on the Sirt2-dependent deacetylation of an in vivo substrate in a physiological environment.
Small interfering RNA (siRNA) is potent and highly specific for gene silencing.
However, 3 and 4 are potent and isoforms-specific Sirt2 inhibitors, and especially 4 appears promising for the development of side effect-free Sirt2 inhibitors, with adding suitable polar groups to this scaffold being a first and obvious optimization step.
