Search Results - "Couñago, Rafael M."

Dysregulation of transition metal ion homeostasis is the molecular basis for cadmium toxicity in Streptococcus pneumoniae by Begg, Stephanie L., Eijkelkamp, Bart A., Luo, Zhenyao, Couñago, Rafael M., Morey, Jacqueline R., Maher, Megan J., Ong, Cheryl-lynn Y., McEwan, Alastair G., Kobe, Bostjan, O’Mara, Megan L., Paton, James C., McDevitt, Christopher A.

“…Cadmium is a transition metal ion that is highly toxic in biological systems. Although relatively rare in the Earth’s crust, anthropogenic release of cadmium…”
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Development of the First Covalent Monopolar Spindle Kinase 1 (MPS1/TTK) Inhibitor by M. Serafim, Ricardo A, da Silva Santiago, André, Schwalm, Martin P, Hu, Zexi, dos Reis, Caio V, Takarada, Jessica E, Mezzomo, Priscila, Massirer, Katlin B, Kudolo, Mark, Gerstenecker, Stefan, Chaikuad, Apirat, Zender, Lars, Knapp, Stefan, Laufer, Stefan, Couñago, Rafael M, Gehringer, Matthias

“…Monopolar spindle kinase 1 (MPS1/TTK) is a key element of the mitotic checkpoint and clinically evaluated as a target in the treatment of aggressive tumors…”
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Rational Exploration of 2,4-Diaminopyrimidines as DHFR Inhibitors Active against Mycobacterium abscessus and Mycobacterium avium, Two Emerging Human Pathogens by Andrade Meirelles, Matheus, Almeida, Vitor M., Sullivan, Jaryd R., de Toledo, Ian, dos Reis, Caio Vinicius, Cunha, Micael Rodrigues, Zigweid, Rachel, Shim, Abraham, Sankaran, Banumathi, Woodward, Elijah L., Seibold, Steve, Liu, Lijun, Mian, Mohammad Rasel, Battaile, Kevin P., Riley, Jennifer, Duncan, Christina, Simeons, Frederick R. C., Ferguson, Liam, Joji, Halimatu, Read, Kevin D., Lovell, Scott, Staker, Bart L., Behr, Marcel A., Pilli, Ronaldo A., Couñago, Rafael M.

“…Nontuberculous mycobacteria (NTM) are emerging human pathogens linked to severe pulmonary diseases. Current treatments involve the prolonged use of multiple…”
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More than an Amide Bioisostere: Discovery of 1,2,4-Triazole-containing Pyrazolo[1,5‑a]pyrimidine Host CSNK2 Inhibitors for Combatting β‑Coronavirus Replication by Ong, Han Wee, Yang, Xuan, Smith, Jeffery L., Dickmander, Rebekah J., Brown, Jason W., Havener, Tammy M., Taft-Benz, Sharon, Howell, Stefanie, Sanders, Marcia K., Capener, Jacob L., Couñago, Rafael M., Chang, Edcon, Krämer, Andreas, Moorman, Nathaniel J., Heise, Mark, Axtman, Alison D., Drewry, David H., Willson, Timothy M.

“…The pyrazolo­[1,5-a]­pyrimidine scaffold is a promising scaffold to develop potent and selective CSNK2 inhibitors with antiviral activity against…”
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Imperfect coordination chemistry facilitates metal ion release in the Psa permease by Couñago, Rafael M, Ween, Miranda P, Begg, Stephanie L, Bajaj, Megha, Zuegg, Johannes, O'Mara, Megan L, Cooper, Matthew A, McEwan, Alastair G, Paton, James C, Kobe, Bostjan, McDevitt, Christopher A

“…The PsaA binding protein delivers Mn 2+ to the human pathogen Streptococcus pneumoniae . Structural and biochemical studies now explain its metal specificity,…”
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AdcA and AdcAII employ distinct zinc acquisition mechanisms and contribute additively to zinc homeostasis in Streptococcus pneumoniae by Plumptre, Charles D., Eijkelkamp, Bart A., Morey, Jacqueline R., Behr, Felix, Couñago, Rafael M., Ogunniyi, Abiodun D., Kobe, Bostjan, O'Mara, Megan L., Paton, James C., McDevitt, Christopher A.

“…Summary Streptococcus pneumoniae is a globally significant human pathogen responsible for nearly 1 million deaths annually. Central to the ability of S…”
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Hinge Binder Scaffold Hopping Identifies Potent Calcium/Calmodulin-Dependent Protein Kinase Kinase 2 (CAMKK2) Inhibitor Chemotypes by Eduful, Benjamin J, O’Byrne, Sean N, Temme, Louisa, Asquith, Christopher R. M, Liang, Yi, Picado, Alfredo, Pilotte, Joseph R, Hossain, Mohammad Anwar, Wells, Carrow I, Zuercher, William J, Catta-Preta, Carolina M. C, Zonzini Ramos, Priscila, Santiago, André de S, Couñago, Rafael M, Langendorf, Christopher G, Nay, Kévin, Oakhill, Jonathan S, Pulliam, Thomas L, Lin, Chenchu, Awad, Dominik, Willson, Timothy M, Frigo, Daniel E, Scott, John W, Drewry, David H

“…CAMKK2 is a serine/threonine kinase and an activator of AMPK whose dysregulation is linked with multiple diseases. Unfortunately, STO-609, the tool inhibitor…”
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WNT Activates the AAK1 Kinase to Promote Clathrin-Mediated Endocytosis of LRP6 and Establish a Negative Feedback Loop by Agajanian, Megan J., Walker, Matthew P., Axtman, Alison D., Ruela-de-Sousa, Roberta R., Serafin, D. Stephen, Rabinowitz, Alex D., Graham, David M., Ryan, Meagan B., Tamir, Tigist, Nakamichi, Yuko, Gammons, Melissa V., Bennett, James M., Couñago, Rafael M., Drewry, David H., Elkins, Jonathan M., Gileadi, Carina, Gileadi, Opher, Godoi, Paulo H., Kapadia, Nirav, Müller, Susanne, Santiago, André S., Sorrell, Fiona J., Wells, Carrow I., Fedorov, Oleg, Willson, Timothy M., Zuercher, William J., Major, Michael B.

“…β-Catenin-dependent WNT signal transduction governs development, tissue homeostasis, and a vast array of human diseases. Signal propagation through a…”
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Chemical Space Exploration of Oxetanes by Alves, Fernando Rodrigues de Sá, Couñago, Rafael M, Laufer, Stefan

“…This paper focuses on new derivatives bearing an oxetane group to extend accessible chemical space for further identification of kinase inhibitors. The ability…”
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Strategic Fluorination to Achieve a Potent, Selective, Metabolically Stable, and Orally Bioavailable Inhibitor of CSNK2 by Ong, Han Wee, Yang, Xuan, Smith, Jeffery L, Taft-Benz, Sharon, Howell, Stefanie, Dickmander, Rebekah J, Havener, Tammy M, Sanders, Marcia K, Brown, Jason W, Couñago, Rafael M, Chang, Edcon, Krämer, Andreas, Moorman, Nathaniel J, Heise, Mark, Axtman, Alison D, Drewry, David H, Willson, Timothy M

“…The host kinase casein kinase 2 (CSNK2) has been proposed to be an antiviral target against β-coronaviral infection. To pharmacologically validate CSNK2 as a…”
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(S)‐ML‐SA1 Activates Autophagy via TRPML1‐TFEB Pathway by Cunha, Micael R., Do Amaral, Bruno S., Takarada, Jéssica E., Valderrama, Gabriel V., Batista, Andrea N. L., Batista, João M., Cass, Quezia B., Couñago, Rafael M., Massirer, Katlin B.

“…Autophagic flux plays a crucial role in various diseases. Recently, the lysosomal ion channel TRPML1 has emerged as a promising target in lysosomal storage…”
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Evolution of the B3 DNA binding superfamily: new insights into REM family gene diversification by Romanel, Elisson A C, Schrago, Carlos G, Couñago, Rafael M, Russo, Claudia A M, Alves-Ferreira, Márcio

“…The B3 DNA binding domain includes five families: auxin response factor (ARF), abscisic acid-insensitive3 (ABI3), high level expression of sugar inducible…”
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In Depth Analysis of Kinase Cross Screening Data to Identify CAMKK2 Inhibitory Scaffolds by O'Byrne, Sean N, Scott, John W, Pilotte, Joseph R, Santiago, André da S, Langendorf, Christopher G, Oakhill, Jonathan S, Eduful, Benjamin J, Couñago, Rafael M, Wells, Carrow I, Zuercher, William J, Willson, Timothy M, Drewry, David H

“…The calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) activates CAMK1, CAMK4, AMPK, and AKT, leading to numerous physiological responses. The…”
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SGC-AAK1-1: A Chemical Probe Targeting AAK1 and BMP2K by Wells, Carrow, Couñago, Rafael M, Limas, Juanita C, Almeida, Tuanny L, Cook, Jeanette Gowen, Drewry, David H, Elkins, Jonathan M, Gileadi, Opher, Kapadia, Nirav R, Lorente-Macias, Alvaro, Pickett, Julie E, Riemen, Alexander, Ruela-de-Sousa, Roberta R, Willson, Timothy M, Zhang, Cunyu, Zuercher, William J, Zutshi, Reena, Axtman, Alison D

“…Inhibitors based on a 3-acylaminoindazole scaffold were synthesized to yield potent dual AAK1/BMP2K inhibitors. Optimization furnished a small molecule…”
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Discovery of pyrazolo[3,4-d]pyrimidines as novel mitogen-activated protein kinase kinase 3 (MKK3) inhibitors by Takarada, Jéssica E, Cunha, Micael R, Almeida, Vitor M, Vasconcelos, Stanley N S, Santiago, André S, Godoi, Paulo H, Salmazo, Anita, Ramos, Priscila Z, Fala, Angela M, de Souza, Lucas R, Da Silva, Italo E P, Bengtson, Mario H, Massirer, Katlin B, Couñago, Rafael M

“…The dual-specificity protein kinase MKK3 has been implicated in tumor cell proliferation and survival, yet its precise role in cancer remains inconclusive. A…”
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Structural Analysis of Inhibitor Binding to CAMKK1 Identifies Features Necessary for Design of Specific Inhibitors by Santiago, André da Silva, Couñago, Rafael M., Ramos, Priscila Zonzini, Godoi, Paulo H. C., Massirer, Katlin B., Gileadi, Opher, Elkins, Jonathan M.

“…The calcium/calmodulin-dependent protein kinases (CAMKKs) are upstream activators of CAMK1 and CAMK4 signalling and have important functions in neural…”
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Development of dihydropyrrolopyridinone-based PKN2/PRK2 chemical tools to enable drug discovery by Scott, Fiona, Fala, Angela M., Takarada, Jessica E., Ficu, Mihaela P., Pennicott, Lewis E., Reuillon, Tristan D., Couñago, Rafael M., Massirer, Katlin B., Elkins, Jonathan M., Ward, Simon E.

“…[Display omitted] The Protein Kinase N proteins (PKN1, PKN2 and PKN3) are Rho GTPase effectors. They are involved in several biological processes such as…”
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Novel Dihydropteridinone Derivatives As Potent Inhibitors of the Understudied Human Kinases Vaccinia-Related Kinase 1 and Casein Kinase 1δ/ε by de Souza Gama, Fernando H., Dutra, Luiz A., Hawgood, Michael, dos Reis, Caio Vinícius, Serafim, Ricardo A. M., Ferreira, Marcos A., Teodoro, Bruno V. M., Takarada, Jéssica Emi, Santiago, André S., Balourdas, Dimitrios-Ilias, Nilsson, Ann-Sofie, Urien, Bruno, Almeida, Vitor M., Gileadi, Carina, Ramos, Priscila Z., Salmazo, Anita, Vasconcelos, Stanley N. S., Cunha, Micael R., Mueller, Susanne, Knapp, Stefan, Massirer, Katlin B., Elkins, Jonathan M., Gileadi, Opher, Mascarello, Alessandra, Lemmens, Bennie B. L. G., Guimarães, Cristiano R. W., Azevedo, Hatylas, Couñago, Rafael M.

“…Vaccinia-related kinase 1 (VRK1) and the δ and ε isoforms of casein kinase 1 (CK1) are linked to various disease-relevant pathways. However, the lack of tool…”
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Identification of potential inhibitors of casein kinase 2 alpha of Plasmodium falciparum with potent in vitro activity by Tomaz, Kaira C P, Tavella, Tatyana A, Borba, Joyce V B, Salazar-Alvarez, Luis C, Levandoski, João E, Mottin, Melina, Sousa, Bruna K P, Moreira-Filho, José T, Almeida, Vitor M, Clementino, Leandro C, Bourgard, Catarina, Massirer, Katlin B, Couñago, Rafael M, Andrade, Carolina H, Sunnerhagen, Per, Bilsland, Elizabeth, Cassiano, Gustavo C, Costa, Fabio T M

“…Drug resistance to commercially available antimalarials is a major obstacle in malaria control and elimination, creating the need to find new antiparasitic…”
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Structural characterization of human Vaccinia-Related Kinases (VRK) bound to small-molecule inhibitors identifies different P-loop conformations by Couñago, Rafael M., Allerston, Charles K., Savitsky, Pavel, Azevedo, Hatylas, Godoi, Paulo H., Wells, Carrow I., Mascarello, Alessandra, de Souza Gama, Fernando H., Massirer, Katlin B., Zuercher, William J., Guimarães, Cristiano R. W., Gileadi, Opher

“…The human genome encodes two active Vaccinia-related protein kinases (VRK), VRK1 and VRK2. These proteins have been implicated in a number of cellular…”
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