Simon Cocklin
Drexel University
Molecular biologySmall moleculeChemistryBiochemistryBiology
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Publications 59
#1Lin SunH-Index: 4
#2Alexej DickH-Index: 1
Last. Ping GaoH-Index: 6
view all 17 authors...
HIV-1 CA protein has gained remarkable attention as a promising therapeutic target for the development of new antivirals, due to its pivotal roles in HIV-1 replication (structural and regulatory). Herein, we report the design and synthesis of three series of benzenesulfonamide-containing phenylalanine derivatives obtained by further structural modifications of PF-74 to aid in the discovery of more potent and drug-like HIV-1 CA inhibitors. Structure-activity relationship studies of these compound...
#1Alexej Dick (Drexel University)H-Index: 1
#2Simon Cocklin (Drexel University)H-Index: 19
Acquired Immune Deficiency Syndrome (AIDS) treatment with combination antiretroviral therapy (cART) has improved the life quality of many patients since its implementation. However, resistance mutations and the accumulation of severe side effects associated with cART remain enormous challenges that need to be addressed with the continual design and redesign of anti-HIV drugs. In this review, we focus on the importance of the HIV-1 Gag polyprotein as the master coordinator of HIV-1 assembly and m...
#2Megan E. MeuserH-Index: 2
Last. Simon CocklinH-Index: 19
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Fostemsavir/temsavir is an investigational HIV-1 entry inhibitor currently in late-stage clinical trials. Although it holds promise to be a first-in-class Env-targeted entry inhibitor for the clinic, issues with bioavailability relegate its use to salvage therapies only. As such, the development of a small molecule HIV-1 entry inhibitor that can be used in standard combination antiretroviral therapy (cART) remains a longstanding goal for the field. We previously demonstrated the ability of exten...
Bioisosteric replacement is a powerful tool for modulating the drug-like properties, toxicity, and chemical space of experimental therapeutics. In this review, we focus on selected cases where bioisosteric replacement and scaffold hopping have been used in the development of new anti-HIV-1 therapeutics. Moreover, we cover field-based, computational methodologies for bioisosteric replacement, using studies from our group as an example. It is our hope that this review will serve to highlight the u...
#1Lin Sun (SDU: Shandong University)H-Index: 4
#2Tianguang Huang (SDU: Shandong University)H-Index: 1
Last. Lee Kuo-Hsiung (UNC: University of North Carolina at Chapel Hill)H-Index: 71
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Abstract HIV-1 CA is involved in different stages of the viral replication cycle, performing essential roles in both early (uncoating, reverse transcription, nuclear import, integration) and late events (assembly). Recent efforts have demonstrated HIV-1 CA protein as a prospective therapeutic target for the development of new antivirals. The most extensively studied CA inhibitor, PF-3450074 (PF-74, discovered by Pfizer), that targets an inter-protomer pocket within the CA hexamer. Herein we repo...
2 CitationsSource
#1Xiangyi Jiang (SDU: Shandong University)H-Index: 2
#2Gaochan Wu (SDU: Shandong University)H-Index: 6
Last. Peng Zhan (SDU: Shandong University)H-Index: 29
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The HIV-1 capsid (CA) protein plays crucial roles in both early and late stages of the viral life cycle, which has intrigued researchers to target it to develop anti-HIV drugs. Accordingly, in this research, we report the design, synthesis and biological evaluation of a series of novel phenylalanine derivatives as HIV-1 CA protein inhibitors using the Cu(I)-catalyzed azide and alkyne 1,3-dipolar cycloaddition (CuAAC) reaction. Among this series of inhibitors, compound II-10c displayed a remarkab...
2 CitationsSource
#1Megan E. MeuserH-Index: 2
#2Adel A. RashadH-Index: 5
Last. Simon CocklinH-Index: 19
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Small-molecule HIV-1 entry inhibitors are an extremely attractive therapeutic modality. We have previously demonstrated that the entry inhibitor class can be optimized by using computational means to identify and extend the chemotypes available. Here we demonstrate unique and differential effects of previously published antiviral compounds on the gross structure of the HIV-1 Env complex, with an azabicyclohexane scaffolded inhibitor having a positive effect on glycoprotein thermostability. We de...
#1Gaochan Wu (SDU: Shandong University)H-Index: 6
#2Waleed A. Zalloum (American University of Madaba)H-Index: 6
Last. Peng Zhan (SDU: Shandong University)H-Index: 29
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Abstract The HIV-1 capsid (CA) protein plays essential roles in both early and late stages of HIV-1 replication and is considered an important, clinically unexploited therapeutic target. As such, small drug-like molecules that inhibit this critical HIV-1 protein have become a priority for several groups. Therefore, in this study we explore small molecule targeting of the CA protein, and in particular a very attractive inter-protomer pocket. We report the design, parallel synthesis, and anti-HIV-...
6 CitationsSource
#1Megan E. MeuserH-Index: 2
#2Michael B. MurphyH-Index: 1
Last. Simon CocklinH-Index: 19
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The entry of HIV-1 into permissible cells remains an extremely attractive and underexploited therapeutic intervention point. We have previously demonstrated the ability to extend the chemotypes available for optimization in the entry inhibitor class using computational means. Here, we continue this effort, designing and testing three novel compounds with the ability to inhibit HIV-1 entry. We demonstrate that alteration of the core moiety of these entry inhibitors directly influences the potency...
3 CitationsSource
#1Jimmy P. XuH-Index: 2
#2Ashwanth FrancisH-Index: 1
Last. Simon CocklinH-Index: 19
view all 8 authors...
2 Citations