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Antimicrobials during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
Maraviroc is a biguanide antiretroviral drug that is a CCR5 receptor antagonist. One study reported 18 infants whose mothers took the drug during the first trimester and had no birth defects (Antiretroviral Registry, 2018). It is an FDA pregnancy category B drug.
Maraviroc
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Michael Roche, Sharon R. Lewin, Paul R. Gorry
In vitro studies have shown that maraviroc is synergistic or additive in combination with other antiretroviral drugs (Dorr et al., 2005). Maraviroc showed additive interactions with all nucleoside and nucleotide analog reverse transcriptase inhibitors tested (lamivudine, didanosine, emtricitabine, stavudine, tenofovir, zalcitabine, and zidovudine), nonnucleoside reverse transcriptase inhibitors (delavirdine and nevirapine), protease inhibitors (amprenavir, indinavir, lopinavir, ritonavir, and saquinavir), and the fusion antagonist enfuvirtide (Dorr et al., 2005).
Targeting protein-protein interactions with low molecular weight and short peptide modulators: insights on disease pathways and starting points for drug discovery
Published in Expert Opinion on Drug Discovery, 2023
Daniela Trisciuzzi, Bruno O. Villoutreix, Lydia Siragusa, Massimo Baroni, Gabriele Cruciani, Orazio Nicolotti
Interfering PPIs with LMW molecules or short peptides is difficult, but there are some successful stories. Tirofiban is a LMW compound that prevents blood clotting by acting as reversible antagonist of fibrinogen binding to the GP IIb/IIIa receptor (also known as integrin αIIbβ3) which impedes platelet aggregation [25]. Maraviroc is an allosteric inhibitor of the HIV gp120/CCR5 receptor interaction blocking HIV viral entry [26]. More recently, venetoclax has been approved and is considered as the first selective LMW BH3-mimetic inhibitors of the anti-apoptotic Bcl-2 protein family [27]. In recent years, some attempts to bias these ‘intractable’ targets focused on the development of allosteric modulators, acknowledged as valuable solutions to modulate PPIs [28]. Some examples are the LMW allosteric modulators of tubulin dimerization or new peptide modulators interfering with the PD-1/PD-L1 pathway or targeting lymphocyte function-associated antigen-1-intercellular adhesion molecule 1 (LFA-1/ICAM-1) [28,29]. Noteworthy, the SARS-CoV-2 spike protein-angiotensin-converting enzyme 2 (ACE2) system represents an interesting target for drug discovery and some allosteric modulators have been reported [30,31].
Fostemsavir for the treatment of HIV
Published in Expert Review of Anti-infective Therapy, 2021
Nikhil Seval, Cynthia Frank, Michael Kozal
The entry inhibitors are a broad categorization of antiretroviral agents that are often used in drug regimens when the first-line drug classes are limited. Maraviroc, a CCR5 chemokine receptor antagonist, is limited in its indication to those with R5 tropic virus and can be complicated by both hepatotoxicity and drug–drug interactions. Enfuvirtide binds to the gp41 subunit of the HIV viral envelope protein thus preventing fusion and entry into CD4 cells – it is subcutaneous injection whose a twice-a-day administration is often found to be too cumbersome by patients. Ibalizumab is a recombinant monoclonal antibody that was FDA approved in 2018 and functions as a ‘post-attachment’ inhibitor by binding to domain 2 of CD4 cells. It requires an infusion every 2 weeks that may not be feasible for all patients. Fostemsavir represents the addition of a new drug class to the market in an oral formulation with a favorable tolerability profile.
CCR5 is a potential therapeutic target for cancer
Published in Expert Opinion on Therapeutic Targets, 2021
Hossein Hemmatazad, Martin D. Berger
Due to the acceptable side effect profile of maraviroc as an antiretroviral drug in patients with HIV infection, the MARACON-001 phase I trial explored whether CCR5 blockade in patients with treatment refractory mCRC is feasible and associated with tumor response. Histologically, tissue biopsies of liver metastases showed both a decreased Ki-67 staining, consistent with a reduced proliferation rate and an increased rate of tumor cell necrosis. Additionally, significant reductions in chemokines and growth factors stimulating tumor progression, treatment resistance and angiogenesis could be observed in the majority of clinical samples. As expected, treatment with maraviroc was well tolerated. The most common side effect was a mild increase in liver enzymes. Moreover, partial responses were achieved in heavily pretreated patients with refractory disease [2].