Results 1 to 10 of about 1,267 (159)

Optimizing the Multimerization Properties of Quinoline-Based Allosteric HIV-1 Integrase Inhibitors [PDF]

Viruses
Allosteric HIV-1 Integrase (IN) Inhibitors or ALLINIs bind at the dimer interface of the IN, away from the enzymatic catalytic site, and disable viral replication by inducing over-multimerization of IN.
Jian Sun, Jacques J. Kessl
doaj   +6 more sources

The structural and mechanistic bases for the viral resistance to allosteric HIV-1 integrase inhibitor pirmitegravir [PDF]

mBio
Allosteric HIV-1 integrase (IN) inhibitors (ALLINIs) are investigational antiretroviral agents that potently impair virion maturation by inducing hyper-multimerization of IN and inhibiting its interaction with viral genomic RNA. The pyrrolopyridine-based
Tung Dinh, Zahira Tber, Juan S. Rey, Seema Mengshetti, Arun S. Annamalai, Reed Haney, Lorenzo Briganti, Franck Amblard, James R. Fuchs, Peter Cherepanov, Kyungjin Kim, Raymond F. Schinazi, Juan R. Perilla, Baek Kim, Mamuka Kvaratskhelia   +14 more
doaj   +9 more sources

Allosteric Integrase Inhibitor Influences on HIV-1 Integration and Roles of LEDGF/p75 and HDGFL2 Host Factors [PDF]

Viruses, 2022
Allosteric integrase (IN) inhibitors (ALLINIs), which are promising preclinical compounds that engage the lens epithelium-derived growth factor (LEDGF)/p75 binding site on IN, can inhibit different aspects of human immunodeficiency virus 1 (HIV-1 ...
Parmit Kumar Singh, Wen Li, Gregory J. Bedwell, Hind J. Fadel, Eric M. Poeschla, Alan N. Engelman   +5 more
doaj   +5 more sources

A highly potent and safe pyrrolopyridine-based allosteric HIV-1 integrase inhibitor targeting host LEDGF/p75-integrase interaction site.

PLoS Pathogens, 2021
Allosteric integrase inhibitors (ALLINIs) are a class of experimental anti-HIV agents that target the noncatalytic sites of the viral integrase (IN) and interfere with the IN-viral RNA interaction during viral maturation.
Tatsuya Maehigashi, Seohyun Ahn, Uk-Il Kim, Jared Lindenberger, Adrian Oo, Pratibha C Koneru, Bijan Mahboubi, Alan N Engelman, Mamuka Kvaratskhelia, Kyungjin Kim, Baek Kim   +10 more
doaj   +5 more sources

A Conformational Escape Reaction of HIV-1 against an Allosteric Integrase Inhibitor. [PDF]

J Virol, 2020
Understanding the mechanism of HIV-1 resistance to anti-HIV-1 drugs could lead to the development of novel drugs with increased efficiency, resulting in more effective ART. ART composed of more potent and long-acting anti-HIV-1 drugs can greatly improve drug adherence and also provide HIV-1 prevention such as preexposure prophylaxis.
Nakamura T, Nakamura T, Amano M, Miyakawa T, Yamagata Y, Matsuoka M, Nakata H.   +6 more
europepmc   +8 more sources

Discovery and Preclinical Profiling of GSK3839919, a Potent HIV-1 Allosteric Integrase Inhibitor. [PDF]

ACS Med Chem Lett, 2022
Allosteric HIV-1 integrase inhibitors (ALLINIs) have been of interest recently because of their novel mechanism of action. Strategic modifications to the C5 moiety of a class of 4-(4,4-dimethylpiperidinyl)-2,6-dimethylpyridinyl ALLINIs led to the identification of a tetrahydroisoquinoline heterocycle as a suitable spacer element to project the distal ...
Parcella K, Parcella K, Wang T, Eastman K, Zhang Z, Yin Z, Patel M, Tu Y, Zheng BZ, Walker MA, Saulnier MG, Frennesson D, Bowsher M, Gillis E, Peese K, Belema M, Cianci C, Dicker IB, McAuliffe B, Ding B, Falk P, Simmermacher J, Parker DD, Sivaprakasam P, Kish K, Lewis H, Hanumegowda U, Jenkins S, Kadow JF, Krystal M, Meanwell NA, Naidu BN.   +31 more
europepmc   +5 more sources

Allosteric integrase inhibitor potency is determined through the inhibition of HIV-1 particle maturation. [PDF]

Proc Natl Acad Sci U S A, 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 KA, Wang H, Slaughter A, Feng L, Kessl JJ, Koh Y, Wang W, Ballandras-Colas A, Patel PA, Fuchs JR, Kvaratskhelia M, Engelman A.   +11 more
europepmc   +6 more sources

Erratum for Dinh et al., “The structural and mechanistic bases for the viral resistance to allosteric HIV-1 integrase inhibitor pirmitegravir” [PDF]

mBio
Tung Dinh, Zahira Tber, Juan S. Rey, Seema Mengshetti, Arun S. Annamalai, Reed Haney, Lorenzo Briganti, Franck Amblard, James R. Fuchs, Peter Cherepanov, Kyungjin Kim, Raymond F. Schinazi, Juan R. Perilla, Baek Kim, Mamuka Kvaratskhelia   +14 more
doaj   +3 more sources

Multi-Substituted Quinolines as HIV-1 Integrase Allosteric Inhibitors [PDF]

Viruses, 2022
Allosteric HIV-1 integrase (IN) inhibitors, or ALLINIs, are a new class of antiviral agents that bind at the dimer interface of the IN, away from the enzymatic catalytic site and block viral replication by triggering an aberrant multimerization of the viral enzyme.
Long P. Dinh, Jianping Sun, Courtney D. Glenn, Krunal Patel, Julie A. Pigza, Matthew G. Donahue, Larry Yet, Jacques J. Kessl   +7 more
openalex   +4 more sources

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 Rebensburg, Ashley C. Hoyte, Jared Lindenberger, Daniel Adu‐Ampratwum, Ross C. Larue, Michael F. Wempe, Alan Engelman, Dmitry Lyumkis, James R. Fuchs, Ronald M. Levy, Gregory B. Melikyan, Mamuka Kvaratskhelia   +14 more
  +6 more sources