Results 1 to 10 of about 58,275 (292)

Structure-based development of novel adenylyl cyclase inhibitors. [PDF]

J Med Chem, 2008
In mammals, the second messenger cAMP is synthesized by a family of transmembrane isoforms (tmACs) and one known cytoplasmic enzyme, "soluble" adenylyl cyclase (sAC). Understanding the individual contributions of these families to cAMP signaling requires tools which can distinguish them.
Schlicker C, Rauch A, Hess KC, Kachholz B, Levin LR, Buck J, Steegborn C.   +6 more
europepmc   +6 more sources

Isoform selectivity of adenylyl cyclase inhibitors: characterization of known and novel compounds. [PDF]

J Pharmacol Exp Ther, 2013
Nine membrane-bound adenylyl cyclase (AC) isoforms catalyze the production of the second messenger cyclic AMP (cAMP) in response to various stimuli. Reduction of AC activity has well documented benefits, including benefits for heart disease and pain.
Brand CS, Hocker HJ, Gorfe AA, Cavasotto CN, Dessauer CW.   +4 more
europepmc   +6 more sources

Assessing potency and binding kinetics of soluble adenylyl cyclase (sAC) inhibitors to maximize therapeutic potential

Frontiers in Physiology, 2022
In mammalian cells, 10 different adenylyl cyclases produce the ubiquitous second messenger, cyclic adenosine monophosphate (cAMP). Amongst these cAMP-generating enzymes, bicarbonate (HCO3−)-regulated soluble adenylyl cyclase (sAC; ADCY10) is uniquely ...
Thomas Rossetti, Jacob Ferreira, Lubna Ghanem, Hannes Buck, Clemens Steegborn, Robert W. Myers, Peter T. Meinke, Lonny R. Levin, Jochen Buck   +8 more
doaj   +4 more sources

Development of a High-Throughput Screening Paradigm for the Discovery of Small-Molecule Modulators of Adenylyl Cyclase: Identification of an Adenylyl Cyclase 2 Inhibitor [PDF]

The Journal of Pharmacology and Experimental Therapeutics, 2013
Adenylyl cyclase (AC) isoforms are implicated in several physiologic processes and disease states, but advancements in the therapeutic targeting of AC isoforms have been limited by the lack of potent and isoform-selective small-molecule modulators. The discovery of AC isoform-selective small molecules is expected to facilitate the validation of AC ...
Jason M. Conley, Cameron S. Brand, Amy S. Bogard, Evan P.S. Pratt, Ruqiang Xu, Gregory H. Hockerman, Rennolds S. Ostrom, Carmen Dessauer, Val J. Watts   +8 more
semanticscholar   +6 more sources

Metal Coordination-Based Inhibitors of Adenylyl Cyclase:  Novel Potent P-Site Antagonists

Journal of Medicinal Chemistry, 2003
The adenylyl cyclases (ACs) are a family of intracellular enzymes associated with signal transduction by virtue of their ability to convert ATP to cAMP. The catalytic mechanism of this transformation proceeds through initial binding of ATP to the so-called purine binding site (P-site) of the enzyme followed by metal-mediated cyclization with loss of ...
Daniel E. Levy, Ming Bao, Diana B. Cherbavaz, James Tomlinson, David M. Sedlock, C J Homcy, Robert M. Scarborough   +6 more
semanticscholar   +4 more sources

Pro-nucleotide Inhibitors of Adenylyl Cyclases in Intact Cells [PDF]

Journal of Biological Chemistry, 2004
9-substituted adenine derivatives with protected phosphoryl groups were synthesized and tested as inhibitors of adenylyl cyclase in isolated enzyme and intact cell systems. Protected 3'-phosphoryl derivatives of 2',5'-dideoxyadenosine (2',5'-dd-Ado) and beta-l-2',5'-dd-Ado, protected 5'-phosphoryl derivatives of beta-l-2',3'-dd-Ado, and protected ...
Wolfgang H.G. Laux, Praveen Pande, Ilana Shoshani, Junyuan Gao, Valérie Boudou-Vivet, Gilles Gosselin, Roger A. Johnson   +6 more
openalex   +4 more sources

Exchange of Substrate and Inhibitor Specificities between Adenylyl and Guanylyl Cyclases [PDF]

Journal of Biological Chemistry, 1998
The active sites of guanylyl and adenylyl cyclases are closely related. The crystal structure of adenylyl cyclase and modeling studies suggest that specificity for ATP or GTP is dictated in part by a few amino acid residues, invariant in each family, that interact with the purine ring of the substrate.
Roger K. Sunahara, Annie Beuve, J.J.G. Tesmer, Stephen R. Sprang, David L. Garbers, Alfred G. Gilman   +5 more
openalex   +3 more sources

Activation of Adenylyl Cyclase Causes Stimulation of Adenosine Receptors

Cellular Physiology and Biochemistry, 2018
Background/Aims: Signaling of Gs protein-coupled receptors (GsPCRs) is accomplished by stimulation of adenylyl cyclase, causing an increase of the intracellular cAMP concentration, activation of the intracellular cAMP effectors protein kinase A (PKA) and
Thomas Pleli, Antonia Mondorf, Nerea Ferreiros, Dominique Thomas, Karel Dvorak, Ricardo M. Biondi, Dagmar Meyer zu Heringdorf, Stefan Zeuzem, Gerd Geisslinger, Herbert Zimmermann, Oliver Waidmann, Albrecht Piiper   +11 more
doaj   +2 more sources

Functional Non‐Nucleoside Adenylyl Cyclase Inhibitors

Chemical Biology & Drug Design, 2014
In this study, we describe the synthesis of novel functional non‐nucleoside adenylyl cyclase inhibitors, which can be easily modified with thiol containing biomolecules such as tumour targeting structures. The linkage between inhibitor and biomolecule contains cleavable bonds to enable efficient intracellular delivery in the reductive milieu of the ...
Lelle, Marco, Hameed, Abdul, Ackermann, Lisa-Maria, Kaloyanova, Stefka, Wagner, Manfred, Berisha, Filip, Nikolaev, Viacheslav O., Peneva, Kalina   +7 more
openaire   +4 more sources

Characterization of Plasmodium falciparum adenylyl cyclase-β and its role in erythrocytic stage parasites. [PDF]

PLoS ONE, 2012
The most severe form of human malaria is caused by the parasite Plasmodium falciparum. The second messenger cAMP has been shown to be important for the parasite's ability to infect the host's liver, but its role during parasite growth inside erythrocytes,
Eric Salazar, Erin M Bank, Nicole Ramsey, Kenneth C Hess, Kirk W Deitsch, Lonny R Levin, Jochen Buck   +6 more
doaj   +2 more sources