Results 301 to 310 of about 2,040,864 (360)

PI5P4K inhibitors: promising opportunities and challenges

The FEBS Journal, EarlyView.
Developing inhibitors is like climbing a steep, challenging mountain. PI5P4K inhibitors hold significant promise for the treatment of cancer, immune disorders, and neurological diseases. However, the path to success is fraught with hurdles, and researchers are therefore required to apply their expertise to overcome critical “checkpoints.” While some ...
Koh Takeuchi, Lisa Nagase, Shun Kageyama, Hirotaka Kanoh, Masashi Oshima, Aki Ogawa‐Iio, Yoshiki Ikeda, Yuki Fujii, Sei Kondo, Natsuki Osaka, Takeshi Masuda, Tsukasa Ishihara, Yoshikazu Nakamura, Yoshihisa Hirota, Takehiko Sasaki, Toshiya Senda, Atsuo T. Sasaki   +16 more
wiley   +1 more source

Covalent-Allosteric Inhibitors: Do We Get the Best of Both Worlds? [PDF]

J Med Chem
Tao H, Yang B, Farhangian A, Xu K, Li T, Zhang ZY, Li J.   +6 more
europepmc   +1 more source

A signal transduction blind spot: the function of adenylyl cyclase transmembrane domains

The FEBS Journal, EarlyView.
Transmembrane adenylyl cyclases (tmACs) are essential for synthesising the universal second messenger cyclic AMP. All tmACs share a common topology that includes a large 12‐helix transmembrane (TM) domain. This domain accounts for ~ 35% of the coding sequence but its function is still an open question.
Ryan S. Dowsell, Matthew G. Gold
wiley   +1 more source

Study on SHP2 Conformational Transition and Structural Characterization of Its High-Potency Allosteric Inhibitors by Molecular Dynamics Simulations Combined with Machine Learning. [PDF]

Molecules
Wujieti B, Hao M, Liu E, Zhou L, Wang H, Zhang Y, Cui W, Chen B.   +7 more
europepmc   +1 more source

Allosteric modulation of protein kinase A in individuals affected by NLPD‐PKA, a neurodegenerative disease in which the PRKAR1B L50R variant is expressed

The FEBS Journal, EarlyView.
In healthy neurons, Protein kinase A (PKA) forms a tetrameric holoenzyme enabling precise allosteric regulation. We characterized a novel neurodegenerative disease, neuronal loss, and parkinsonism driven by PRKAR1B mutation (NLPD‐PKA), demonstrating disrupted holoenzyme assembly, reduced cooperativity, and increased catalytic subunit nuclear ...
Tal Benjamin‐Zukerman, Valeria Pane, Rania Safadi‐Safa, Meir Solomon, Varda Lev‐Ram, Mohammad Aboraya, Anwar Dakwar, Daniela Bertinetti, Andrew Hoy, Merel O. Mol, John van Swieten, Rodrigo Maillard, Friedrich W. Herberg, Ronit Ilouz   +13 more
wiley   +1 more source

Uvarinol and Dichamanetin Derived from <i>Uvaria chamae</i> as Potential Dual-Site Inhibitors Against PBP2a in Methicillin Resistant <i>Staphylococcus aureus</i>: An In Silico Study. [PDF]

Pharmaceuticals (Basel)
Agbebi EA, Adeyemi SO, Adewale AI, Ajofoyinbo OS, Olugbogi EA, Oyinloye OM, Anuoluwa IA, Agbebi TO, Ajiboye BO, Oyinloye BE.   +9 more
europepmc   +1 more source

The disease‐linked R336C mutation in cystathionine β‐synthase disrupts communication with the PLP cofactor, yet maintains the enzyme's overall structural integrity

The FEBS Journal, EarlyView.
Cystathionine β‐synthase (CBS) is an essential enzyme involved in cysteine metabolism. The mutation R336C, associated with severe homocystinuria and of high incidence in Qatar, reduces its activity. Our research shows that this mutation does not destabilize the enzyme fold but subtly alters the tautomeric equilibrium of the PLP cofactor within the ...
Carolina Conter, Reyes Núñez‐Franco, Duaa Walid Al‐Sadeq, Carmen Fernández‐Rodríguez, Naroa Goikoetxea‐Usandizaga, Gheyath K. Nasrallah, Michail Nomikos, Maria Luz Martinez‐Chantar, Alessandra Astegno, Gonzalo Jiménez‐Osés, Luis Alfonso Martínez‐Cruz   +10 more
wiley   +1 more source

A somatic multiple myeloma mutation unravels a mechanism of oligomerization‐mediated product inhibition in GGPPS

The FEBS Journal, EarlyView.
Geranylgeranyl diphosphate synthase (GGPPS) plays a key role in multiple myeloma biology. Using crystallography, mass spectrometry, and fluorescence spectroscopy, this study shows that a somatic multiple myeloma cell line mutation destabilizes inter‐dimer interactions, resulting in increased GGPPS activity by facilitating product releas.
Ruba Yehia, Jasmína Mária Portašiková, Rut Mor Yosef, Benny Da'adoosh, Alan Kádek, Petr Man, Moshe Giladi, Yoni Haitin   +7 more
wiley   +1 more source

Intracellular GPCR modulators enable precision pharmacology. [PDF]

NPJ Drug Discov
Krumm BE, Roth BL.
europepmc   +1 more source

PI3Kγ in Tumour Inflammation: Bridging Immune Response and Cancer Progression—A Mini‐Review

Immunology, EarlyView.
Myeloid cell PI3Kγ can be activated by G Protein‐Coupled Receptors or Receptor Tyrosine Kinases. Once activated, PI3Kγ promotes integrin activation as well as Akt and mTOR activation, thereby promoting transcription of immune‐suppressive and pro‐angiogenic factors, such as Arginase, IL‐10, TGFβ and VEGF‐A.
Anghesom Ghebremedhin, Judith A. Varner
wiley   +1 more source