98%
921
2 minutes
20
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1002/cmdc.201200197 | DOI Listing |
Bioorg Med Chem Lett
September 2025
Galapagos SASU, 102 avenue Gaston Roussel, 93230 Romainville, France. Electronic address:
The salt-inducible kinase (SIK) family encompasses three isoforms, SIK1, SIK2, and SIK3, which are members of the AMP-activated protein kinase (AMPK) family of serine/threonine protein kinases. SIK inhibition has emerged as a potential therapeutic approach across multiple indications, as SIKs regulate a diverse set of physiological processes such as metabolism, bone remodeling, immune response, malignancies, skin pigmentation, and circadian rhythm. Within isoform-specific SIK inhibitors there is a need to understand the distinct role of each protein, and here we describe the first SIK1 selective inhibitors.
View Article and Find Full Text PDFJ Enzyme Inhib Med Chem
December 2025
Department of Pharmaceutical Sciences and Natural Products, Central University of Punjab, Bathinda, India.
The mitogen-activated protein kinase (MAPK) pathway-also known as the RAS/RAF/MEK/ERK pathway-is a critical signalling cascade involved in regulating cell growth, proliferation, and survival. First discovered in the early 1980s, the pathway's extracellular signal-regulated kinase (ERK) subfamily was identified in the 1990s. The ERK family includes several isoforms-ERK1, ERK2, ERK3, ERK5, and ERK6-with ERK1 (MAPK3) and ERK2 (MAPK1) being the most well-characterised and playing central roles in MAPK signalling.
View Article and Find Full Text PDFChem Biol Drug Des
September 2025
School of Chemistry and Physics, University of KwaZulu-Natal, Durban, South Africa.
Molecular hybridization of isoniazid with hydrophobic aromatic moieties represents a promising strategy for the development of novel anti-tubercular therapeutics. In this study, a series of hybrid molecules (5a-i) was synthesized by linking isoniazid with aromatic sulfonate esters via a hydrazone bridge. Molecular docking studies revealed that these compounds interact effectively with the catalytic triad of the InhA enzyme (Y158, F149, and K165), suggesting their potential as InhA inhibitors.
View Article and Find Full Text PDFSAR QSAR Environ Res
August 2025
Center for Medical Artificial Intelligence, Shandong University of Traditional Chinese Medicine, Qingdao, China.
Phosphorylation plays an important role in the activity of CDK2 and inhibitor binding, but the corresponding molecular mechanism is still insufficiently known. To address this gap, the current study innovatively integrates molecular dynamics (MD) simulations, deep learning (DL) techniques, and free energy landscape (FEL) analysis to systematically explore the action mechanisms of two inhibitors (SCH and CYC) when CDK2 is in a phosphorylated state and bound state of CyclinE. With the help of MD trajectory-based DL, key functional domains such as the loops L3 loop and L7 are successfully identified.
View Article and Find Full Text PDFChem Biodivers
September 2025
Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Molecular, Structural and Translational Virology Research Group, KU Leuven, Leuven, Belgium.
The human chemokine receptor 8 (CCR8) received attention as target for the treatment of various autoimmune disorders. Phenoxybenzylpiperidine analogues are known to act as CCR8 agonists, although their structure-activity relationship (SAR) has been studied to a limited extent. In this study, the SAR of phenoxybenzylpiperidinyl analogues was explored in a systematic way by fusion or insertion of various heterocyclic groups on the piperidinyl ring, yielding a set of 21 novel phenoxybenzylpiperidinyl derivatives.
View Article and Find Full Text PDF