The most potent analogue 16l was broadly active against all the tested cancer cell lines (IC50 = 3.16 7.93 μM).
These results suggest that tryptamine and tyramine are broadly active antagonists of insect ORs.
Due to their unusual antiviral mechanism, imino sugars should be complementary to the other antiviral approaches and have the advantage of being broadly active.
Similarly, a class of 7-chloro-4-quinolinyl hydrazones was found to be broadly active against a range of Leishmania promastigotes with seven compounds (72) demonstrating EC50 values of <0.5 μg/mL.
The evidence that extended 3'UTRs, and small RNAs derived from them, are also present in somatic tissues implies that this mechanism may be broadly active, but play a much more prominent role in differentiation of spermatocytes.
Vav, another RhoGEF composed of several domains that have been implicated in protein protein interactions in addition to the DH and PH domains, has been shown to be broadly active with several Rho GTPases, such as Rac, RhoA, and Cdc42.
Our current results with naturally occurring amines, together with previous reports with synthetic compounds strongly suggest that: 1) allosteric antagonism of odorant activation of ORs is a general property of Orco antagonists; 2) Orco antagonists are broadly active at ORs of many insect species; and 3) Orco is an important target for the development of novel insect repellants.
Conservation of the ω-hexatoxin family of toxins over this wide range of environments and differing prey distributions implies that there has been strong evolutionary pressure to maintain these peptides as part of the venom arsenal, which is perhaps not surprising given that they are broadly active against many different arthropods [ 11, 17, 37].
We identified inhibitors against each of these targets including Wortmannin, a well-known PI3K inhibitor, Rottlerin and Chelerythrine Chloride which are broadly-active PKC inhibitors, and antiporter inhibitors including amiloride derivatives such as EIPA [25].
In organisms from yeast to humans, H4K16ac is broadly associated with active genes, and the Histone Acetyl Transferase (HAT) that writes the modification is required for viability [ 18- 21].
