Abemaciclib, a Recent Novel FDA-Approved Small Molecule Inhibiting Cyclin-Dependant Kinase 4/6 for the Treatment of Metastatic Breast Cancer: A Mini-Review

Abemaciclib (Verzerio®) is a cell cycle inhibitor of both CDK4 and CDK6. In 2017, abemaciclib was approved by the Food and Drug Administration (FDA) and, in 2018 by the European Medicines Agency (EMA) for the treatment of postmenopausal women with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2−) advanced breast cancer. In this mini-review, we provide a series of information for respectively their targets and its selectivity, results on preclinical trial, clinical phase I, II and III trials, and some perspectives. We also describe the batch and flow steps used for the synthesis of this cancer drug.

Molecular Docking Study of the Binding Interaction of Hydroxychloroquine, Dexamethasone and Other Anti-Inflammatory Drugs with SARS-CoV-2 Protease and SARS-CoV-2 Spikes Glycoprotein

Aims: The outbreak of the novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still accountable for millions of deaths worldwide and declared as a global pandemic by the World Health Organisation. Despite efforts, there is still limited evidence available on a successful potent inhibitor with a low toxicity profile that can aid in the prevention and/or treatment of COVID-19. This study will focus on four main aspects: 1) screening 19 Food Drug and Administration (FDA) approved drugs using computational molecular docking;2) assessing drug toxicity profiles using biological data;3) recommending potential therapies against COVID-19 and 4) supplementing currently used therapies. Methods: 19 FDA approved drugs were investigated against the crystal structure of SARS-CoV-2 protease (6LU7) and SARS-CoV-2 glycoprotein (6VXX) using a computational molecular docking software, Molecular Operating Environment (MOE). Separately, on MOE, 6LU7 and 6VXX were loaded, prepared, and the binding pockets located. The drug’s canonical SMILES were imported, minimised, and docked on the prepared proteins using a search algorithm to establish the highest stability conformation. Drugs were ranked depending on binding properties and biological data to assess safety;steric clashes and voids in the binding site were also analysed. Results and discussion: Out of the nineteen (19) FDA approved drugs, 18 inhibited 6LU7 and 13 inhibited 6VXX. High-ranked drugs based on binding properties for 6LU7 were hydroxychloroquine, dexamethasone, naproxen, etoricoxib, and ibuprofen. For 6VXX were hydroxychloroquine, celecoxib, etoricoxib, meloxicam, and parecoxib. Considering safety profile, the top 3 drugs in descending order for 6LU7 were etoricoxib, naproxen and dexamethasone and for 6VXX were etoricoxib, meloxicam, and parecoxib. Compared to the literature, the results were consistent for dexamethasone which was effective against 6LU7. However, for hydroxychloroquine and ibuprofen, there was conflicting literature regarding safety and efficacy. Conclusion and future work: The findings suggest that against COVID-19 etoricoxib might be effective as a therapeutic and prophylactic measure. Naproxen and dexamethasone would be more effective as treatment only while meloxicam and parecoxib as prophylaxis. However, future studies are needed to validate these findings. Compared to previous literature, the findings in this study also support the use of dexamethasone over hydroxychloroquine and ibuprofen for COVID-19 based on the binding and safety properties. Despite this, future research should explore the impressive binding properties displayed by hydroxychloroquine and ibuprofen to aid in developing a new drug against COVID-19.

Computational Investigation of the Interaction of Anti-Influenza Drugs with CoVID-19 Protein

Coronavirus (CoVID-19) is a new outbreak of coronavirus disease which started in the Wuhan, China, the spread of this virus has now reached a global stage, urgent need is therefore needed to find new drug molecules which can either be used as a first aid intervention or slow down the multiplication rate of the virus within the system. In order to address this, this research looked into the existing antiviral drugs and screened them for their inhibitory properties towards the CoVID-19 protein. Recently, the crystal structure of the CoVID-19 (6LU7) protein has been established, this gives us the possible drug target site in CoVID-19. The binding affinity of the six compounds was screened using MOE (Molecular Operating Environment) software, four compounds (Zanamivir, Peramivir, Rimantidine, and Oseltamivir) out these six compounds have been approved by the Food Drug and Administration (FDA). The molecular docking calculation, Higher Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital (LUMO) calculation were used to hypothesise the bioactivity of the FDA approved drug against the CoVID-19 protein. The calculation showed that Pimodivir tops the list of the anti influenza drug which can be used as first aid treatment for patient. Apart from Pimodivir, Laninamivir Octanoate is also a very good drug which might be used to inhibit CoVID-19 protein. It was also discovered that based on binding property of Rimantadine, it might be suitable for Fragment Based Drug Design (FBDD) approach which might lead to the discovery of completely new drug entity. Stability of the new protein structure was studied using GROMACS molecular dynamic simulation software. The results showed that the stability of the protein structure was achieved over a range of time, this confirmed that 6LU7 crystal structure might be a suitable protein crystal structure suitable for the development of new drug towards the treatment of CoVID-19. Finally, based on the molecular docking result, Pimodivir and Laninamivir Octanoate might be useful in the treatment of infected patient.

Real-World Evidence Supporting New Drug Review and Approval in European Union and Its Enlightenment to China

Objective To analyze the application of real-world evidence(RWE)in the field of medicine in European Union,and provide suggestions for RWE supporting the review and approval of new drugs in China.Methods The European Medicines Agency(EMA)and other databases were used to search relevant documents for analyzing the European Union’s new drug review and approval process with the support of RWE.Results and Conclusion The European Union carrying out new drug review and approval with the support of RWE has just begun.The decision-making process includes three stages such as new drug research and development,review,and approval.However,there are some challenges in data quality,research methods,evidence sufficiency,and research process of RWE supporting the European Union in reviewing and approving new drugs.At present,RWE can accurately grasp the clinical effects of drugs and improve the safety and effectiveness in the process of assisting the review and approval of new drugs.At the same time,RWE also can promote the development and application of Traditional Chinese Medicine(TCM)and help find out the potential value of TCM such as new indications.

A Systemic Review on Topical Marketed Formulations, Natural Products, and Oral Supplements to Prevent Androgenic Alopecia: A Review

Androgens have an intense consequence on the human scalp and body hair.Scalp hair sprouts fundamentally in awol of androgens whereas the body hair hike is vulnerable to the activity of androgens.Androgenetic alopecia(AGA)invoked as males emulate Alopecia due to the cause of the dynamic reduction of scalp hair.Androgens are medium of terminus growth of hair although the body.Local and system androgens convert the extensive terminal follicles into lesser vellus like structure.The out start of this type of alopecia is intensely irregular and the reason behind this existence of enough circulating steroidal hormones androgens and due to genetic predisposition.Effective treatments are available in the market as well as under clinical and preclinical testing.Many herbal formulations are also available but not FDA approved.Different conventional and NDDS formulations are already available in the market.To avoid various systemic side effects of both Finasteride and Minoxidil,topical formulations and natural products(nutrients,minerals,vitamins)now a days are being widely used to treat Androgenic alopecia.CAM(complementary and alternative medicine)provides the option to elect favorable,low-risk,adjuvant and alternative therapies.Herein,we offer a widespread review of topical marketed formulations,natural products,and CAM treatment options for AGA.