Finding the rules for successful drug optimisation

Yusof, Iskander; Shah, Falgun; Hashimoto, Tatsu; Segall, Matthew D.; Greene, Nigel

doi:10.1016/j.drudis.2014.01.005

Cited by 34 publications

(26 citation statements)

References 19 publications

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“…Harpagide 5-O-β-D-glucopyranoside demonstrated approvingly a very good partition coefficient ( Table 3 ). This suggests that it can be efficiently transported across cell membranes, as passive diffusion through a cell membrane is a key element of transcellular absorption (Doak et al, 2014 ; Yusof et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

Targeting the initiation and termination codons of SARS-CoV-2 spike protein as possible therapy against COVID-19: the role of novel harpagide 5-O-β-D-glucopyranoside from Clerodendrum volubile P Beauv. (Labiatae)

Erukainure

Atolanı

Muhammad

et al. 2020

Journal of Biomolecular Structure and Dynamics

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The global spread of the coronavirus infections disease − 2019 (COVID-19) and the search for new drugs from natural products particularly from plants are receiving much attention recently. In this study, the therapeutic potential of a new iridoid glycoside isolated from the leaves of Clerodendrum volubile against COVID-19 was investigated. Harpagide 5-O-β-D-glucopyranoside (HG) was isolated, characterised and investigated for its druglikeness, optimized geometry, and pharmacokinetics properties. Its immunomodulatory was determined by chemiluminescence assay using polymorphonuclear neutrophils (PMNs) in addition to T-cell proliferation assay. In silico analysis was used in determining its molecular interaction with severe acute respiratory syndrome coronavirus-2 (SARS-COV-2). HG displayed potent druglikeness properties, with no inhibitory effect on cytochrome P 450 (1A2, 2C19, 2C9, 2D6 and 3A4) and a predicted LD 50 of 2000 mg/kg. Its 1 H-NMR chemical shifts showed a little deviation of 0.01 and 0.11 ppm for H-4 and H-9, respectively. HG significantly suppressed oxidative bursts in PMNs, while concomitantly inhibiting T-cell proliferation. It also displayed a very strong binding affinity with the translation initiation and termination sequence sites of spike (S) protein mRNA of SARS-COV-2, its gene product, and host ACE2 receptor. These results suggest the immunomodulatory properties and anti-SARS-COV-2 potentials of HG which can be explored in the treatment and management of COVID-19. Communicated by Ramaswamy H. Sarma

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Section: Discussionmentioning

confidence: 99%

Targeting the initiation and termination codons of SARS-CoV-2 spike protein as possible therapy against COVID-19: the role of novel harpagide 5-O-β-D-glucopyranoside from Clerodendrum volubile P Beauv. (Labiatae)

Erukainure

Atolanı

Muhammad

et al. 2020

Journal of Biomolecular Structure and Dynamics

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“…From the rules viewpoint, our introduced rules can strongly be approved in terms of biology. 26 The strongest rules with the frequency of 14231 and 5443 belong to two isoforms of the CYP family, which is one of the most important enzymes in drug metabolism. The CYP family encompasses several wellknown enzymes involved in the metabolism of nutrients, drugs, and toxicants.…”

Section: Discussionmentioning

confidence: 99%

“…widely been used in the field of biology and medicine. 26,27 For instance, in the field of pharmacology, this procedure has been used to identify the associations of drugs' features in traditional Chinese medicine drug pairs. 26,28 This section describes our approach in terms of mining DDIs based on the biomedical data.…”

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confidence: 99%

Identification and ranking of important bio-elements in drug-drug interaction by Market Basket Analysis

2019

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Introduction: Drug-drug interactions (DDIs) are the main causes of the adverse drug reactions and the nature of the functional and molecular complexity of drugs behavior in the human body make DDIs hard to prevent and threat. With the aid of new technologies derived from mathematical and computational science, the DDI problems can be addressed with a minimum cost and effort. The Market Basket Analysis (MBA) is known as a powerful method for the identification of co-occurrence of matters for the discovery of patterns and the frequency of the elements involved. Methods: In this research, we used the MBA method to identify important bio-elements in the occurrence of DDIs. For this, we collected all known DDIs from DrugBank. Then, the obtained data were analyzed by MBA method. All drug-enzyme, drug-carrier, drug-transporter and drug-target associations were investigated. The extracted rules were evaluated in terms of the confidence and support to determine the importance of the extracted bio-elements. Results: The analyses of over 45 000 known DDIs revealed over 300 important rules from 22 085 drug interactions that can be used in the identification of DDIs. Further, the cytochrome P450 (CYP) enzyme family was the most frequent shared bio-element. The extracted rules from MBA were applied over 2 000 000 unknown drug pairs (obtained from FDA approved drugs list), which resulted in the identification of over 200 000 potential DDIs. Conclusion: The discovery of the underlying mechanisms behind the DDI phenomena can help predict and prevent the inadvertent occurrence of DDIs. Ranking of the extracted rules based on their association can be a supportive tool to predict the outcome of unknown DDIs.

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“…Figure 1d (parameters [11][12][13][14][15][16][17][18] highlighted that nearly all in vitro ADME criteria achieved >50% pass rates. This correlated well with rodent PK because more than half the compounds evaluated in vivo met preliminary bioavailability and clearance cutoffs (Fig.…”

Section: Lead Criteria Analysismentioning

confidence: 99%

“…Contract research organizations (CROs) have been widely adopted to reduce costs so that internal medicinal chemists can focus beyond synthetic challenges [10]. In addition, improved data mining [11,12], computational efficiency, predictive in vitro absorption, distribution, metabolism, and excretion (ADME) [13,14], and multiple parameter optimization (MPO) [15,16], along with expanded knowledge of desirable drug properties [17], have provided us with many useful tools to develop medicinal chemistry programs. Despite all these advances, recent statistics show that effectiveness and output in drug discovery have not greatly improved [18].…”

Section: Introductionmentioning

confidence: 99%

Lead optimization attrition analysis (LOAA): a novel and general methodology for medicinal chemistry

Munson

Lieberman

Tserlin

et al. 2015

Drug Discovery Today

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Finding the rules for successful drug optimisation

Cited by 34 publications

References 19 publications

Targeting the initiation and termination codons of SARS-CoV-2 spike protein as possible therapy against COVID-19: the role of novel harpagide 5-O-β-D-glucopyranoside from Clerodendrum volubile P Beauv. (Labiatae)

Targeting the initiation and termination codons of SARS-CoV-2 spike protein as possible therapy against COVID-19: the role of novel harpagide 5-O-β-D-glucopyranoside from Clerodendrum volubile P Beauv. (Labiatae)

Identification and ranking of important bio-elements in drug-drug interaction by Market Basket Analysis

Lead optimization attrition analysis (LOAA): a novel and general methodology for medicinal chemistry

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