Results 11 to 20 of about 989 (99)

Indole-based allosteric inhibitors of HIV-1 integrase [PDF]

Bioorganic & Medicinal Chemistry Letters, 2016
Employing a scaffold hopping approach, a series of allosteric HIV-1 integrase (IN) inhibitors (ALLINIs) have been synthesized based on an indole scaffold. These compounds incorporate the key elements utilized in quinoline-based ALLINIs for binding to the IN dimer interface at the principal LEDGF/p75 binding pocket.
Pratiq A. Patel, Nina Kvaratskhelia, Yara Mansour, Janet Antwi, Lei Feng, Pratibha Koneru, Mathew J. Kobe, Nivedita Jena, Guqin Shi, Mosaad S. Mohamed, Chenglong Li, Jacques J. Kessl, James R. Fuchs   +12 more
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Allosteric Inhibitor Development Targeting HIV‐1 Integrase [PDF]

ChemMedChem, 2011
AbstractHIV‐1 integrase (IN) is one of three essential enzymes for viral replication, and is a focus of ardent antiretroviral drug discovery and development efforts. Diligent research has led to the development of the strand‐transfer‐specific chemical class of IN inhibitors, with two compounds from this group, raltegravir and elvitegravir, advancing ...
Nouri Neamati, Laith Q. Al-Mawsawi
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HIV-1 integrase tetramers are the antiviral target of pyridine-based allosteric integrase inhibitors

eLife, 2019
Allosteric HIV-1 integrase (IN) inhibitors (ALLINIs) are a promising new class of antiretroviral agents that disrupt proper viral maturation by inducing hyper-multimerization of IN. Here we show that lead pyridine-based ALLINI KF116 exhibits striking selectivity for IN tetramers versus lower order protein oligomers.
Pratibha C Koneru, Ashwanth C Francis, Nanjie Deng, Stephanie V Rebensburg, Ashley C Hoyte, Jared Lindenberger, Daniel Adu-Ampratwum, Ross C Larue, Michael F Wempe, Alan N Engelman, Dmitry Lyumkis, James R Fuchs, Ronald M Levy, Gregory B Melikyan, Mamuka Kvaratskhelia   +14 more
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Allosteric HIV-1 Integrase Inhibitors Lead to Premature Degradation of the Viral RNA Genome and Integrase in Target Cells [PDF]

Journal of Virology, 2017
ABSTRACT Recent evidence indicates that inhibition of HIV-1 integrase (IN) binding to the viral RNA genome by allosteric integrase inhibitors (ALLINIs) or through mutations within IN yields aberrant particles in which the viral ribonucleoprotein complexes (vRNPs) are eccentrically localized outside the capsid lattice.
Madison, Michaela K, Lawson, Dana Q, Elliott, Jennifer, Ozanturk, Ayse Naz, Koneru, Pratibha C, Townsend, Dana, Errando, Manel, Kvaratskhelia, Mamuka, Kutluay, Sebla B   +8 more
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The HIV-1 integrase-LEDGF allosteric inhibitor MUT-A: resistance profile, impairment of virus maturation and infectivity but without influence on RNA packaging or virus immunoreactivity [PDF]

Retrovirology, 2017
Background HIV-1 Integrase (IN) interacts with the cellular co-factor LEDGF/p75 and tethers the HIV preintegration complex to the host genome enabling integration.
Céline Amadori, Yme Ubeles van der Velden, Damien Bonnard, Igor Orlov, Nikki van Bel, Erwann Le Rouzic, Laia Miralles, Julie Brias, Francis Chevreuil, Daniele Spehner, Sophie Chasset, Benoit Ledoussal, Luzia Mayr, François Moreau, Felipe García, José Gatell, Alessia Zamborlini, Stéphane Emiliani, Marc Ruff, Bruno P. Klaholz, Christiane Moog, Ben Berkhout, Montserrat Plana, Richard Benarous   +23 more
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An Isoquinoline Scaffold as a Novel Class of Allosteric HIV-1 Integrase Inhibitors [PDF]

ACS Medicinal Chemistry Letters, 2019
Allosteric HIV-1 integrase inhibitors (ALLINIs) are a new class of potential antiretroviral therapies with a unique mechanism of action and drug resistance profile. To further extend this class of inhibitors via a scaffold hopping approach, we have synthesized a series of analogues possessing an isoquinoline ring system. Lead compound 6l binds in the v-
Tyler A. Wilson, Pratibha C. Koneru, Stephanie V. Rebensburg, Jared J. Lindenberger, Matthew J. Kobe, Nicholas T. Cockroft, Daniel Adu-Ampratwum, Ross C. Larue, Mamuka Kvaratskhelia, James R. Fuchs   +9 more
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Allosteric integrase inhibitor potency is determined through the inhibition of HIV-1 particle maturation [PDF]

Proceedings of the National Academy of Sciences, 2013
Integration is essential for HIV-1 replication, and the viral integrase (IN) protein is an important therapeutic target. Allosteric IN inhibitors (ALLINIs) that engage the IN dimer interface at the binding site for the host protein lens epithelium-derived growth factor (LEDGF)/transcriptional coactivator p75 are an emerging class of small molecule ...
Jurado, Kellie, Wang, Hao, Slaughter, Alison, Feng, Lei, Kessl, Jacques, Koh, Yasuhiro, Wang, Weifeng, Ballandras-Colas, Allison, Patel, Pratiq, Fuchs, James, Kvaratskhelia, Mamuka, Engelman, Alan   +11 more
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Multimode, Cooperative Mechanism of Action of Allosteric HIV-1 Integrase Inhibitors [PDF]

Journal of Biological Chemistry, 2012
The multifunctional HIV-1 enzyme integrase interacts with viral DNA and its key cellular cofactor LEDGF to effectively integrate the reverse transcript into a host cell chromosome. These interactions are crucial for HIV-1 replication and present attractive targets for antiviral therapy.
Kessl, Jacques, Jena, Nivedita, Koh, Yasuhiro, Taskent-Sezgin, Humeyra, Slaughter, Alison, Feng, Lei, de Silva, Suresh, Wu, Li, Le Grice, Stuart F. J., Engelman, Alan, Fuchs, James, Kvaratskhelia, Mamuka   +11 more
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A Critical Role of the C-terminal Segment for Allosteric Inhibitor-induced Aberrant Multimerization of HIV-1 Integrase [PDF]

Journal of Biological Chemistry, 2014
Allosteric HIV-1 integrase (IN) inhibitors (ALLINIs) are a promising class of antiretroviral agents for clinical development. Although ALLINIs promote aberrant IN multimerization and inhibit IN interaction with its cellular cofactor LEDGF/p75 with comparable potencies in vitro, their primary mechanism of action in infected cells is through inducing ...
Venkatasubramanian Dharmarajan, Jacques J. Kessl, Alison Slaughter, Nikoloz Shkriabai, Lei Feng, Ross C. Larue, James R. Fuchs, Mamuka Kvaratskhelia, Patrick R. Griffin   +8 more
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Dual inhibition of HIV-1 replication by integrase-LEDGF allosteric inhibitors is predominant at the post-integration stage [PDF]

Retrovirology, 2013
Abstract Background LEDGF/p75 (LEDGF) is the main cellular cofactor of HIV-1 integrase (IN). It acts as a tethering factor for IN, and targets the integration of HIV in actively transcribed gene regions of chromatin. A recently developed class of IN allosteric inhibitors can inhibit the LEDGF-IN interaction.
Le Rouzic, Erwann, Bonnard, Damien, Chasset, Sophie, Bruneau, Jean-Michel, Chevreuil, Francis, Le Strat, Frédéric, Nguyen, Juliette, Beauvoir, Roxane, Amadori, Céline, Brias, Julie, Vomscheid, Sophie, Eiler, Sylvia, Lévy, Nicolas, Delelis, Olivier, Deprez, Eric, Saïb, Ali, Zamborlini, Alessia, Emiliani, Stéphane, Ruff, Marc, Ledoussal, Benoit, Moreau, François, Benarous, Richard   +21 more
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