Results 211 to 220 of about 4,995,094 (293)

Covalent drug discovery: Progress against key targets, emerging strategies and lessons learnt

British Journal of Pharmacology, EarlyView.
Abstract Covalent drug discovery is currently experiencing a boom in industrial and academic interest. To date, at least 75 covalent drugs have received regulatory approval, targeting both traditional target classes and more challenging proteins for which other approaches failed. In many cases, unique aspects of covalent targeting are essential for the
Charles P. Brown, Alan Armstrong, David J. Mann   +2 more
wiley   +1 more source

ENX-101, a GABA_A receptor α2,3,5-selective positive allosteric modulator, displays antiseizure effects in rodent seizure and epilepsy models. [PDF]

Epilepsia
Serrats J, Vadodaria KC, Brubaker W, Barker-Haliski M, White HS, Evrard A, Roucard C, Taylor E, Vanover KE, Cunningham S, Sudarsan V, Rogawski MA.   +11 more
europepmc   +1 more source

Cancer pain: current practice and emerging targets

British Journal of Pharmacology, EarlyView.
Cancer pain (CP) arises from a complex interplay between the tumour and its microenvironment. Many patients experience a mixed pain phenotype that encompasses nociceptive, neuropathic and neuroinflammatory mechanisms, and vary across tumour type and disease stage. Despite decades of intensive research, the mainstay of cancer pain treatment is still non‐
Yi Ye, Marcin Chwistek, Zhiting Gong, Vanessa Uzonwanne, Xiaojie Shi, Arpad Szallasi   +5 more
wiley   +1 more source

Targeting KRAS for cancer therapy

British Journal of Pharmacology, EarlyView.
In recent years, therapeutics targeted against KRAS proto‐oncogene GTPase (KRAS)‐mutant cancers have seen significant progress. Herein we outline the biology and epidemiology of KRAS alterations at the lineage and allele levels, reviewing the clinical evidence for KRASG12C inhibition from the discovery of the recessive switch pocket to sotorasib ...
Jianlong Jia, Ruonan Liu, Tonia A. Adamide, Isis E. Fernandez, Georgios T. Stathopoulos   +4 more
wiley   +1 more source

Peripheral targets for neuropathic pain

British Journal of Pharmacology, EarlyView.
Neuropathic pain represents a significant clinical challenge, with still limited pharmacological approaches to symptomatic relief. This review focuses on molecular targets implicated in neuropathic pain, particularly those involved in peripheral mechanisms. Using the IUPHAR/BPS database of biological targets, their occurrence together with ‘neuropathic
Amirhossein Afsharipour, Cosmin I. Ciotu, Felix J. Resch, Michael J. M. Fischer   +3 more
wiley   +1 more source

Potentiation effects of the positive allosteric modulator PTC‐174 on NMDA receptors in neonatal male rat substantia nigra dopaminergic neurons

British Journal of Pharmacology, EarlyView.
Abstract Background and Purpose Positive allosteric modulators bind to secondary binding sites on the receptor and alter receptor conformation and activation, changing agonist potency and efficacy. PTC‐174 is a novel NMDA receptor positive allosteric modulator that particularly enhances activity of receptors containing GluN2C or GluN2D subunits.
Bangyuan Liu, Alasdair J. Gibb
wiley   +1 more source

Preclinical pharmacology of alogabat: a novel GABA_A-α5 positive allosteric modulator targeting neurodevelopmental disorders with impaired GABA_A signaling. [PDF]

Front Pharmacol
Cecere G, Ballard TM, Knoflach F, Honer M, Hipp JF, Garces P, Mueggler T, Künnecke B, Bruns A, Prinssen EP, Schoenenberger P, Janz P, Redondo R, Biemans B, Knust H, Olivares-Morales A, Brigo A, Schulz JM, Bertrand D, Saxe M, O'Connor EC, Hernandez MC.   +21 more
europepmc   +1 more source

Chemoproteomic discovery of a brain‐penetrant, covalent NLRP3 inhibitor that binds a novel allosteric pocket

British Journal of Pharmacology, EarlyView.
NLRP3 is a promising inflammatory target, but existing inhibitors lack diversity and brain penetrance, and none are approved. Using chemoproteomics, we discovered a novel series that binds to Cys463 in a previously uncharacterized pocket. Compounds showed nanomolar potency, brain exposure, and in vivo suppression of IL‐1β, supporting neuroinflammatory ...
Donald C. Rogness, Evelyn P. Sievert, Vincent F. Vartabedian, Steffen M. Bernard, Erick Aitchison, William Tao, Mikaela Lindvall, Jing Qian, Christie L. Eissler, Brian E. Nordin, Benjamin D. Horning, Cian Kingston, Kelsey N. Lamb, Joshua C. Bell, Bingwen Lu, Jonathan Pollock, Jun Shi, Roli Khattri, David S. Weinstein, Matthew P. Patricelli, Brian N. Cook, Gabriel M. Simon   +21 more
wiley   +1 more source

NMDA receptor subunit‐dependent analysis of radiprodil inhibition in neonatal male rat substantia nigra dopaminergic neurons

British Journal of Pharmacology, EarlyView.
Abstract Background and Purpose Radiprodil is a GluN2B subunit selective NMDA receptor negative allosteric modulator which is currently under clinical investigation as a possible anti‐epileptic drug for paediatric use. Our goal was to investigate the inhibition of dopaminergic neuron NMDA responses by radiprodil.
Bangyuan Liu, Alasdair J. Gibb
wiley   +1 more source