Pharmacokinetic stability of macrocyclic peptide triazole HIV‐1 inactivators alone and in liposomes

Aneja, Rachna; Grigoletto, Antonella; Nangarlia, Aakansha; Rashad, Adel A.; Wrenn, Steven P.; Jacobson, Jeffrey M.; Pasut, Gianfranco; Chaiken, Irwin M.

doi:10.1002/psc.3155

Cited by 12 publications

(4 citation statements)

References 35 publications

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“…Without chemical modifications, peptides have a short circulating half-life of several minutes. They are rapidly degraded by protease enzymes (29)(30)(31) and eliminated by renal filtration (50). We recognized that a peptide's rapid renal clearance could be advantageous as a drug carrier to dispose most systemically administered drugs in urine for treating NMIBC and reducing the unwanted systemic side-effects.…”

Section: Discussionmentioning

confidence: 99%

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A Urinary Drug-Disposing Approach as an Alternative to Intravesical Chemotherapy for Treating Nonmuscle Invasive Bladder Cancer

Bellat

Michel

Thomas³

et al. 2022

Cancer Research

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The standard treatment of non-muscle invasive bladder cancer (NMIBC) is transurethral resection of the tumors, followed by intravesical therapy (IT), which comprises a direct instillation of a solution of Bacillus Calmette-Guérin vaccine or chemotherapy into the bladder.However, the recurrence rate in this disease remains unacceptably high. IT is a local treatment that fails to reach tumors developed in the upper urinary tract (ureter and renal pelvis). The catheterization procedure required for IT is invasive, painful, and poses an increased infection risk resulting in poor patient quality of life and compliance. There is an unmet need for a potent, comprehensive, and non-invasive option. Without chemical modifications, peptides are rapidly removed by renal clearance. This "shortcoming" can be advantageous when used as a drug carrier for directing therapy to NMIBC. Here we develop a urinary drug-disposing (UDD) approach to improve NMIBC treatment. A 12-amino acid bio-inert peptide (Bdd) that can be exclusively eliminated via renal filtration was generated for delivering the microtubule inhibitor DM1 to NMIBC with minimal non-specific accumulation in other organs. The UDD approach prolonged survival of mice bearing human bladder tumors. Unlike IT, the treatment was given non-invasively (intravenously). Furthermore, it was more effective at suppressing tumor growth than clinically used IT (mitomycin) and safer than free DM1. The application of this urinary drug-disposing approach to treat kidney tumors and deliver other drugs such as doxorubicin was also demonstrated. Overall, the rapid renal clearance of peptides can be exploited to direct cancer therapies to the urinary system.Research.

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Section: Discussionmentioning

confidence: 99%

“…Further, without chemical modifications, a peptide is not a good drug candidate or carrier. It displays unfavorable pharmacokinetics (PK), is rapidly degraded by protease enzymes (29)(30)(31), and can be eliminated by renal filtration. In the present studies, we exploited a peptide's Research.…”

Section: Introductionmentioning

confidence: 99%

A Urinary Drug-Disposing Approach as an Alternative to Intravesical Chemotherapy for Treating Nonmuscle Invasive Bladder Cancer

Bellat

Michel

Thomas³

et al. 2022

Cancer Research

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“…In 2021, Yoshida et al reported the solid-phase synthesis and bioactivity evaluation of cherimolacyclopeptide E [ 77 ]. Additional on-resin MW-assisted macrocyclization of peptides via amide coupling was reported by Rashad et al in 2015 [ 78 ] and Aneja et al in 2019 [ 79 ].…”

Section: Microwave-assisted And/or Solid-supported Synthesis Of Macro...mentioning

confidence: 98%

Recent Advances in Macrocyclic Drugs and Microwave-Assisted and/or Solid-Supported Synthesis of Macrocycles

Sun

2022

Molecules

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Macrocycles represent attractive candidates in organic synthesis and drug discovery. Since 2014, nineteen macrocyclic drugs, including three radiopharmaceuticals, have been approved by FDA for the treatment of bacterial and viral infections, cancer, obesity, immunosuppression, etc. As such, new synthetic methodologies and high throughput chemistry (e.g., microwave-assisted and/or solid-phase synthesis) to access various macrocycle entities have attracted great interest in this chemical space. This article serves as an update on our previous review related to macrocyclic drugs and new synthetic strategies toward macrocycles (Molecules, 2013, 18, 6230). In this work, I first reviewed recent FDA-approved macrocyclic drugs since 2014, followed by new advances in macrocycle synthesis using high throughput chemistry, including microwave-assisted and/or solid-supported macrocyclization strategies. Examples and highlights of macrocyclization include macrolactonization and macrolactamization, transition-metal catalyzed olefin ring-closure metathesis, intramolecular C–C and C–heteroatom cross-coupling, copper- or ruthenium-catalyzed azide–alkyne cycloaddition, intramolecular SNAr or SN2 nucleophilic substitution, condensation reaction, and multi-component reaction-mediated macrocyclization, and covering the literature since 2010.

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“…Besides the abovementioned 1,2,3‐triazole–peptide hybrids, some other peptides could serve as potential entry inhibitors binding to HIV‐1 gp120. [ 74–79 ] Among them, the 1,2,3‐triazole–macrocyclic peptide hybrid 27 (EC 50 : 105 nM), which showed enhanced entropically favored binding to Env gp120, was highly active against HIV‐1 BAL strain, so this hybrid warrants further study. [ 79 ]…”

Section: 23‐triazole–peptide Hybridsmentioning

confidence: 99%

1,2,3‐Triazole hybrids with anti‐HIV‐1 activity

Feng

Zheng

Zhao

et al. 2020

Archiv der Pharmazie

103

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The human immunodeficiency virus type 1 (HIV‐1) is the major etiological agent responsible for the acquired immunodeficiency syndrome (AIDS), which is a serious infectious disease and remains one of the most prevalent problems at present. Currently, combined antiretroviral therapy is the primary modality for the treatment and management of HIV/AIDS, but the long‐term use can result in major drawbacks such as the development of multidrug‐resistant viruses and multiple side effects. 1,2,3‐Triazole is the common framework in the development of new drugs, and its derivatives have the potential to inhibit various HIV‐1 enzymes such as reverse transcriptase, integrase, and protease, consequently possessing a potential anti‐HIV‐1 activity. This review covers the recent advances regarding the 1,2,3‐triazole hybrids with potential anti‐HIV‐1 activity; it focuses on the chemical structures, structure–activity relationship, and mechanisms of action, covering articles published from 2010 to 2020.

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Pharmacokinetic stability of macrocyclic peptide triazole HIV‐1 inactivators alone and in liposomes

Cited by 12 publications

References 35 publications

A Urinary Drug-Disposing Approach as an Alternative to Intravesical Chemotherapy for Treating Nonmuscle Invasive Bladder Cancer

A Urinary Drug-Disposing Approach as an Alternative to Intravesical Chemotherapy for Treating Nonmuscle Invasive Bladder Cancer

Recent Advances in Macrocyclic Drugs and Microwave-Assisted and/or Solid-Supported Synthesis of Macrocycles

1,2,3‐Triazole hybrids with anti‐HIV‐1 activity

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