[HTML][HTML] Preclinical characterization of the CDK4/6 inhibitor LY2835219: in-vivo cell cycle-dependent/independent anti-tumor activities alone/in combination with …

…, MJ Lallena, R Torres, RT Ajamie, GN Wishart… - Investigational new …, 2014 - Springer
The G1 restriction point is critical for regulating the cell cycle and is controlled by the Rb
pathway (CDK4/6-cyclin D1-Rb-p16/ink4a). This pathway is important because of its inactivation …

Brain exposure of two selective dual CDK4 and CDK6 inhibitors and the antitumor activity of CDK4 and CDK6 inhibition in combination with temozolomide in an …

TJ Raub, GN Wishart, P Kulanthaivel, BA Staton… - Drug Metabolism and …, 2015 - ASPET
Effective treatments for primary brain tumors and brain metastases represent a major unmet
medical need. Targeting the CDK4/CDK6-cyclin D1-Rb-p16/ink4a pathway using a potent …

Semi-mechanistic pharmacokinetic/pharmacodynamic modeling of the antitumor activity of LY2835219, a new cyclin-dependent kinase 4/6 inhibitor, in mice bearing …

…, RP Beckmann, EM Chan, A De Dios, GN Wishart… - Clinical Cancer …, 2014 - AACR
Wishart … RP Beckmann and GN Wishart have ownership interest (including patents) in
Eli Lilly Stock. No potential conflicts of interest were disclosed by the other authors. …

M1 and m2 muscarinic receptor subtypes regulate antidepressant-like effects of the rapidly acting antidepressant scopolamine

…, C Overshiner, X Li, JT Catlow, GN Wishart… - … of Pharmacology and …, 2014 - ASPET
Scopolamine produces rapid and significant symptom improvement in patients with depression,
and most notably in patients who do not respond to current antidepressant treatments. …

The anti-rheumatic potential of a series of 2, 4-di-substituted-4H-naphtho [1, 2-b] pyran-3-carbonitriles

…, AK Harvey, CA Hicks, AE Kingston, GN Wishart - Bioorganic & Medicinal …, 1995 - Elsevier
A new series of naphtho[1,2-b]pyran-3-carbonitriles with enhanced stability under acid conditions
has been synthesised and examined for antiproliferative and anti-inflammatory activity. …

A novel CDK9 inhibitor shows potent antitumor efficacy in preclinical hematologic tumor models

…, KR Fales, S Carballares, R Torrres, GN Wishart… - Molecular cancer …, 2014 - AACR
DNA-dependent RNA polymerase II (RNAP II) largest subunit RPB1 C-terminal domain (CTD)
kinases, including CDK9, are serine/threonine kinases known to regulate transcriptional …

Identification and characterization of a novel smoothened antagonist for the treatment of cancer with deregulated hedgehog signaling

…, DJ Sall, ML Thompson, T Wilson, GN Wishart… - Cancer research, 2011 - AACR
The Hedgehog (Hh) pathway is a highly conserved signaling system that plays an important
role in embryonic development and tissue homeostasis through regulation of cell …

Abstract B234: LY2835219, a potent oral inhibitor of the cyclin-dependent kinases 4 and 6 (CDK4/6) that crosses the blood-brain barrier and demonstrates in vivo …

…, BA Staton, RT Ajamie, G Sawada, GN Wishart… - Molecular Cancer …, 2011 - AACR
Effective treatments for primary brain tumors and brain metastases represent a major unmet
medical need. The blood-brain barrier (BBB) arises from both a structural barrier and drug …

Discovery of non-covalent dipeptidyl peptidase IV inhibitors which induce a conformational change in the active site

…, SR Pulley, BJ Margolis, GN Wishart… - Bioorganic & medicinal …, 2007 - Elsevier
A series of non-covalent inhibitors of the serine protease dipeptidyl peptidase IV (DPP-IV)
were found to adopt a U-shaped binding conformation in X-ray co-crystallization studies. …

Identification and pharmacological profile of SPP1, a potent, functionally selective and brain penetrant agonist at muscarinic M1 receptors

…, F Pasqui, E Sher, GN Wishart… - British Journal of …, 2019 - Wiley Online Library
Background and Purpose We aimed to identify and develop novel, selective muscarinic M 1
receptor agonists as potential therapeutic agents for the symptomatic treatment of …