PACAP has a potency >100-fold higher than VIP at the recombinant PAC1 receptor, whereas it displays a potency similar to VIP at the recombinant VPAC receptors (VPAC1 and VPAC2) in radioligand binding assays (reviewed in Vaudry et al., 2009; Harmar et al., 2012).
However, it displays better potency than other P2 linked compounds, but is still an order of magnitude less potent than the indolyl quinols with no P2 motif (13– 25).
Moreover, two other promising HDAC inhibitors are givinostat and panobinostat, which have been demonstrated to display potency in HIV infected cells44,45.
These efforts led to the identification of novel αVβ3 inhibitors displaying potency in the subnanomolar range, selectivity versus αIIbβ3 and functional efficacy in relevant cellular assays.
Results of biological studies revealed that the majority of compounds exhibited potent to moderately potent activity and among them, 12 displayed potency comparable to that of the imipramine with %DID of 37.95 and 44.84 in the FST and TST, respectively.
The primary antimycobacterial screening reveals that mono-indolizine mono-salts are displaying potency superior to the second-line antitubercular drugs Cycloserine and Pyrimethamine and, equal as the first line anti-TB Ethambutol.
We describe an efficient and convergent synthesis of a series of (1′S,2R,4′S -3H-4′-azaspiro[benzo[4,5]imidazo[2,1-b]oxazole-2,2′-bicyclo[2.2.2]octanes] displaying potency for the α7 nicotinic acetylcholine receptor (nAChR) and good selectivity vs. the related 5-HT3A receptor.
While our previously studied sulfoximine-based inhibitors display potency of 2.5 nM (IC50) against HIV-1 protease, introduction of the sulfoximine moiety into the asymmetric Indinavir yielded only micromolar inhibition.
Importantly, as expected from the FRET melting assay, after 30 min of UV irradiation the caged compound displayed potency comparable to that of the free, active quadruplex ligand.
Indeed, C6 and C7 were effective agonists at this variant and now displayed potency akin to that at the bovine ortholog (Fig. 7 A, B).
As shown in Table 1, these two compounds, compounds 5 and 6, displayed potency in several of our biochemical assays that was similar to the potency of compound 3 (IC50 values within 5 10-fold).
