287114-24-3Relevant articles and documents
CERAMIDE GALACTOSYLTRANSFERASE INHIBITORS FOR THE TREATMENT OF DISEASE
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, (2019/06/11)
Described herein are compounds, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds to treat or prevent diseases or disorders associated with the enzyme ceramide galactosyltransferase (CGT), such as, for example, lysosomal storage diseases. Examples of lysosomal storage diseases include, for example, Krabbe disease and Metachromatic Leukodystrophy.
Bifunctional Chimera That Coordinately Targets Human Immunodeficiency Virus 1 Envelope gp120 and the Host-Cell CCR5 Coreceptor at the Virus-Cell Interface
Rashad, Adel A.,Song, Li-Rui,Holmes, Andrew P.,Acharya, Kriti,Zhang, Shiyu,Wang, Zhi-Long,Gary, Ebony,Xie, Xin,Pirrone, Vanessa,Kutzler, Michele A.,Long, Ya-Qiu,Chaiken, Irwin
, p. 5020 - 5033 (2018/05/29)
To address the urgent need for new agents to reduce the global occurrence and spread of AIDS, we investigated the underlying hypothesis that antagonists of the HIV-1 envelope (Env) gp120 protein and the host-cell coreceptor (CoR) protein can be covalently joined into bifunctional synergistic combinations with improved antiviral capabilities. A synthetic protocol was established to covalently combine a CCR5 small-molecule antagonist and a gp120 peptide triazole antagonist to form the bifunctional chimera. Importantly, the chimeric inhibitor preserved the specific targeting properties of the two separate chimera components and, at the same time, exhibited low to subnanomolar potencies in inhibiting cell infection by different pseudoviruses, which were substantially greater than those of a noncovalent mixture of the individual components. The results demonstrate that targeting the virus-cell interface with a single molecule can result in improved potencies and also the introduction of new phenotypes to the chimeric inhibitor, such as the irreversible inactivation of HIV-1.
Preparation and activities of macromolecule conjugates of the CCR5 antagonist maraviroc
Asano, Shigehiro,Gavrilyuk, Julia,Burton, Dennis R.,Barbas, Carlos F.
supporting information, p. 133 - 137 (2014/03/21)
CCR5 antagonists are among the most advanced approaches in HIV therapy and may also be relevant to treatment of graft-versus-host disease and Staphylococcus aureus infection. To expand the potential of the only approved CCR5 antagonist, Maraviroc, we studied derivatives that would enable functional linkage of Maraviroc to long-lived carriers. Through targeted synthesis, we discovered an effective linkage site on Maraviroc and demonstrate the potential of these derivatives to prepare potent chemically programmed antibodies and PEGylated derivatives. The resulting compounds effectively neutralized a variety of HIV-1 isolates. Both chemically programmed antibody and PEGylation approaches extend the neutralization activity of serum circulating Maraviroc. Derivation of a successful conjugation strategy for Maraviroc should further enable its use in chemically programmed vaccines, novel bispecific antibodies, and topical microbicides.
