A new potent and selective CDK9 inhibitor induces the expression of the proto-oncogene MYC via a mechanism that depends on the bromodomain protein BRD4.
Emil Dandanell Agerschou, Patrick Flagmeier ... Alexander K Buell
The high affinity α-synuclein-monomer binder AS69 converts into a strong sub-stoichiometric inhibitor of nucleation processes upon formation of the AS69-α-synuclein complex, achieving reduced aggregation in vitro and in vivo.
Targeting the CRL5 ubiquitin ligase complex in combination with CDK9 or MCL1 inhibition could combat innate and acquired resistance of cancer cells to MCL1-targeting therapeutics.
A potent and selective DYRK2 inhibitor has been developed and used as a chemical tool to reveal eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) and stromal interaction molecule 1 (STIM1) are new substrates for DYRK2.
The first-in-class kinase inhibitor, Ibrutinib, destabilizes its autoinhibited Bruton’s tyrosine kinase (BTK) target, and a remote resistance mutation causes global structural changes that activate BTK catalytic activity.
Pratibha C Koneru, Ashwanth C Francis ... Mamuka Kvaratskhelia
Pyridine-based allosteric inhibitors selectively target HIV-1 integrase tetramers and exhibit enhanced antiviral activity against a dolutegravir resistant mutant virus indicating potential clinical benefits for combining these two classes of inhibitors.
Ean Spielvogel, Sook-Kyung Lee ... Ronald Swanstrom
New HIV-1 protease inhibitor designs result in more potent inhibitors with high genetic barriers to resistance and the ability to lead virus evolution down less fit pathways when resistance occurs.
Biochemical and electrophysiological approaches show that the amphetamine derivative ECSI#6 is an uncompetitive inhibitor of the serotonin transporter and thus the first ever characterized ligand of a solute carrier of this type.
New ATP-competitive inhibitors show properties of conformation selection when complexed with the MAP kinase, ERK2, altering movements around the activation loop.
Delayed inhibition precisely balances excitation from arbitrary combinations of CA3 neurons and controls the gain of CA1 output by reducing inhibitory delay with increasing excitation.
