Historical Perspective of Drug Discovery and Development

Ramarao, P.

doi:10.1007/978-981-15-5534-3_1

Cited by 7 publications

(7 citation statements)

References 64 publications

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“…In addition, iron(III)-chelating test also confirmed that the conjugates directly bound iron(III) using chrome azurol sulfonate (CAS) and hexadecyl trimethylammonium bromide (HDTMA) as indicators (see the Supporting Information). Moreover, 86b demonstrated stronger iron chelating capacity than cefiderocol, probably on account of the extra coordination of the sulfur atom in the linker, which might increase the intake of these conjugates and thus enhance the antibacterial activities to a certain extent. − To obtain further insight into the iron binding stoichiometry of our compounds, 86a was examined by MS spectrometry. 86a gave rise to peaks at m / z of 805.0 assigned as [M + H] + (Cald.…”

Section: Resultsmentioning

confidence: 99%

Discovery of YFJ-36: Design, Synthesis, and Antibacterial Activities of Catechol-Conjugated β-Lactams against Gram-Negative Bacteria

Liu,

Kou,

et al. 2024

J. Med. Chem.

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Cefiderocol is the first approved catechol-conjugated cephalosporin against multidrug-resistant Gram-negative bacteria, while its application was limited by poor chemical stability associated with the pyrrolidinium linker, moderate potency against Klebsiella pneumoniae and Acinetobacter baumannii, intricate procedures for salt preparation, and potential hypersensitivity. To address these issues, a series of novel catechol-conjugated derivatives were designed, synthesized, and evaluated. Extensive structure-activity relationships and structure-metabolism relationships (SMR) were conducted, leading to the discovery of a promising compound 86b (Code no. YFJ-36) with a new thioether linker. 86b exhibited superior and broad-spectrum in vitro antibacterial activity, especially against A. baumannii and K. pneumoniae, compared with cefiderocol. Potent in vivo efficacy was observed in a murine systemic infection model. Furthermore, the physicochemical stability of 86b in fluid medium at pH 6−8 was enhanced. 86b also reduced potential the risk of allergy owing to the quaternary ammonium linker. The improved properties of 86b supported its further research and development.

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Section: Resultsmentioning

confidence: 99%

Discovery of YFJ-36: Design, Synthesis, and Antibacterial Activities of Catechol-Conjugated β-Lactams against Gram-Negative Bacteria

Liu,

Kou,

et al. 2024

J. Med. Chem.

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“…From serendipitous drug discovery to Computer-Aided Drug Discovery (CADD), medicinal chemistry has come a long way via peaks and valleys. Though the past years have seen many hardships to bring a new drug to market through many hurdles, it has been reckoned that in this decade, the use of AI will bring out the best of ever [12,13]. Figure 1 presents a brief timeline of advancement in the field of AI.…”

Section: Drug Discovery and Aimentioning

confidence: 99%

A comprehensive review on the application of artificial intelligence in drug discovery.

Sahoo

Dar

2021

TABCJ

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The 21st century is witnessing immense achievements in human history, starting from home science to space science. Artificial Intelligence (AI) is a salient one among these feats, the critical factor of the 4th industrial revolution. Health is the primary and essential asset for the continuity of human civilization on this planet. Not only must we address the deadly existing diseases like Cancer, AIDS, Alzheimer's, heart diseases, gastrointestinal diseases, etc., but on top of that, we must effectively predict, prevent and respond to potential pathogens capable of causing havoc like the recent outbreak caused by SARS-CoV-2. AI-enabled technology with the computational capacity of a computer and reasoning ability of humans saves surplus labor and time that is majorly consumed in target validation, lead optimization, molecular representation, and designing reaction pathways, which traditionally is a decade-long way of searching, visualizing, studying, imagining, experimenting and maintaining a ton of data. This article would focus on how AI will help find the drug-like properties in the compound screening phase predicting the Structure-Activity Relationship (SAR) and ADMET properties in lead identification and optimization phases, sustainable development of chemicals in the synthesis phases up to AI's assistance in the successful conduct of clinical trials and repurposing.

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“…Drug discovery and development dates back to the early days of human civilization, where medicines were derived mainly from plants and supplemented by animal materials and minerals [ 1 ]. These medicines were discovered through a combination of trial and error and observation of human and animal reactions after ingestion [ 1 ].…”

Section: Introductionmentioning

confidence: 99%

D3 Receptor-Targeted Cariprazine: Insights from Lab to Bedside

Barabássy,

Dombi,

Németh

2024

IJMS

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Until the late 1800s, drug development was a chance finding based on observations and repeated trials and errors. Today, drug development must go through many iterations and tests to ensure it is safe, potent, and effective. This process is a long and costly endeavor, with many pitfalls and hurdles. The aim of the present review article is to explore what is needed for a molecule to move from the researcher bench to the patients’ bedside, presented from an industry perspective through the development program of cariprazine. Cariprazine is a relatively novel antipsychotic medication, approved for the treatment of schizophrenia, bipolar mania, bipolar depression, and major depression as an add-on. It is a D3-preferring D3-D2 partial agonist with the highest binding to the D3 receptors compared to all other antipsychotics. Based on the example of cariprazine, there are several key factors that are needed for a molecule to move from the researcher bench to the patients’ bedside, such as targeting an unmet medical need, having a novel mechanism of action, and a smart implementation of development plans.

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Historical Perspective of Drug Discovery and Development

Cited by 7 publications

References 64 publications

Discovery of YFJ-36: Design, Synthesis, and Antibacterial Activities of Catechol-Conjugated β-Lactams against Gram-Negative Bacteria

Discovery of YFJ-36: Design, Synthesis, and Antibacterial Activities of Catechol-Conjugated β-Lactams against Gram-Negative Bacteria

A comprehensive review on the application of artificial intelligence in drug discovery.

D3 Receptor-Targeted Cariprazine: Insights from Lab to Bedside

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