Immunotherapy in hematological malignancies: recent advances and open questions

Over recent years, tremendous advances in immunotherapy approaches have been observed, generating significant clinical progress. Cancer immunotherapy has been shown, in different types of blood cancers, to improve the overall survival of patients. Immunotherapy treatment of hematopoietic malignancies is a newly growing field that has been accelerating over the past years. Several US FDA approved drugs and cell-based therapies are being exploited in the late stage of clinical trials. This review attempt to highlight and discuss the numerous innovative immunotherapy approaches of hematopoietic malignancy ranging from nonmyeloablative transplantation, T-cell immunotherapy, natural killer cells and immune agonist to monoclonal antibodies and vaccination. In addition, a brief discussion on the future advances and accomplishments required to counterpart the current immunotherapeutic approaches for hematopoietic malignancies were also highlighted.

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Targeting COVID-19 in Parkinson’s patients: Drugs repurposed.

Current Medicinal Chemistry ◽

10.2174/0929867327666200903115138 ◽

2020 ◽

Vol 27 ◽

Author(s):

Firoz Anwar ◽

Salma Naqvi ◽

Fahad A. Al-Abbasi ◽

Nauroz Neelofar ◽

Vikas Kumar ◽

...

Keyword(s):

Day Treatment ◽

Treatment Options ◽

Developed Countries ◽

Methyl Transferase ◽

Comt Inhibitors ◽

Mao B ◽

Pharmacokinetic Properties ◽

Us Fda ◽

Approved Drugs ◽

Fda Approved Drugs

: The last couple of months have witnessed the world in a state of virtual standstill. The SARS-CoV-2 virus has overtaken globe to economic and social lockdown. Many patients with COVID-19 have compromised immunity, especially in an aged population suffering from Parkinson disease (PD). Alteration in dopaminergic neurons or deficiency of dopamine in PD patients is the most common symptoms affecting 1% population above the age of 60 years. The compromised immune system and inflammatory manifestation in PD patients make them an easy target. The most common under trial drugs for COVID-19 are Remdesivir, Favipiravir, Chloroquine and Hydroxychloroquine, Azithromycin along with adjunct drugs like Amantadine with some monoclonal antibodies. : Presently, clinically US FDA approved drugs in PD includes Levodopa, catechol-O-methyl transferase (COMT) inhibitors, (Entacapone and Tolcapone), Dopamine agonists (Bromocriptine, Ropinirole, Pramipexole, and Rotigotine), Monoamine oxidase B (MAO-B) inhibitors (Selegiline and Rasagiline), Amantadine and Antimuscarinic drugs. The drugs have established mechanism of action on PD patients with known pharmacodynamics and pharmacokinetic properties along with dose and adverse effects. : Conclusion and relevance of this review focus on the drugs that can be tried for the PD patients with SAR CoV-2 infection, in particular, Amantadine approved by all developed countries a common drug possessing both antiviral properties by downregulation of CTSL, lysosomal pathway disturbance and change in pH necessary to uncoat the viral proteins and antiParkinson properties. The significant prognostic adverse effect of SARS-CoV-2 on PD and the present-day treatment options, clinical presentation and various mechanism is warrant need of the hour.

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Analysis of US FDA-Approved Drugs Containing Sulfur Atoms

Topics in Current Chemistry ◽

10.1007/s41061-018-0184-5 ◽

2018 ◽

Vol 376 (1) ◽

Cited By ~ 124

Author(s):

Kevin A. Scott ◽

Jon T. Njardarson

Keyword(s):

Us Fda ◽

Approved Drugs ◽

Fda Approved Drugs

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Pharmacokinetic drug–drug interactions: an insight into recent US FDA-approved drugs for prostate cancer

Bioanalysis ◽

10.4155/bio-2020-0242 ◽

2020 ◽

Vol 12 (22) ◽

pp. 1647-1664

Author(s):

Siva Nageswara Rao Gajula ◽

Gangireddy Navitha Reddy ◽

Dannarm Srinivas Reddy ◽

Rajesh Sonti

Keyword(s):

Drug Interactions ◽

Therapeutic Index ◽

Aged Patients ◽

Metabolizing Enzymes ◽

Considerable Concentration ◽

Concentration Changes ◽

Us Fda ◽

Approved Drugs ◽

Fda Approved Drugs ◽

Pharmacokinetic Drug

Pharmacokinetic drug–drug interaction is a significant safety and efficiency concern as it results in considerable concentration changes. Drug–drug interactions are a substantial concern in anticancer drugs that possess a narrow therapeutic index. These interactions remain as the principal regulatory obstacle that can lead to termination in the preclinical stage, restrictions in the prescription, dosage adjustments or withdrawal of the drugs from the market. Drug metabolizing enzymes or transporters mediate the majority of clinically relevant drug interactions. Cancer diagnosed aged patients use multiple medications and are more prone to significant drug–drug interactions. This review provides detailed information on clinically relevant drug–drug interactions resulting from drug metabolism by enzymes and transporters with a particular emphasis on recent FDA approved antiprostate cancer drugs.

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COVID-19 pandemic: an overview of epidemiology, pathogenesis, diagnostics and potential vaccines and therapeutics

Therapeutic Delivery ◽

10.4155/tde-2020-0035 ◽

2020 ◽

Vol 11 (4) ◽

pp. 245-268 ◽

Cited By ~ 22

Author(s):

Haneen Amawi ◽

Ghina'a I Abu Deiab ◽

Alaa A A Aljabali ◽

Kamal Dua ◽

Murtaza M Tambuwala

Keyword(s):

Middle East ◽

Clinical Evaluation ◽

Preventive Measures ◽

Vaccine Development ◽

Us Fda ◽

Approved Drugs ◽

Respiratory Coronavirus ◽

Fda Approved Drugs

At the time of writing this review, severe acute respiratory coronavirus syndrome-2 (SARS-CoV-2) has infected more than 2,355,853 patients and resulted in more than 164,656 deaths worldwide (as of 20 April 2020). This review highlights the preventive measures, available clinical therapies and the potential of vaccine development against SARS-CoV-2 by taking into consideration the strong genetic similarities of the 2003 epidemic SARS-CoV. Recent studies are investigating the repurposing of US FDA-approved drugs as there is no available vaccine yet with many attempts under clinical evaluation. Several antivirals, antimalarials and immunomodulators that have shown activity against SARS-CoV and Middle East coronavirus respiratory syndromes are being evaluated. In particular, hydroxychloroquine, remdesivir, favipiravir, arbidol, tocilizumab and bevacizumab have shown promising results. The main aim of this review is to provide an overview of this pandemic and where we currently stand.

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Re-Profiling of US-FDA Approved Drugs for COVID-19 by In-silico Studies

Journal of Bioinformatics and Systems Biology ◽

10.26502/jbsb.5107021 ◽

2021 ◽

Vol 04 (02) ◽

Author(s):

Akash Parab ◽

Dr Gaganjyot Kaur ◽

Abhishek Sharma ◽

Gursewak Bhuller ◽

Sharvari Chitnis ◽

...

Keyword(s):

In Silico ◽

In Silico Studies ◽

Us Fda ◽

Approved Drugs ◽

Fda Approved Drugs

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FDA-approved drugs for multiple sclerosis have no efficacy or disability data in non-Caucasian patients

CNS Spectrums ◽

10.1017/s1092852918001517 ◽

2019 ◽

Vol 24 (03) ◽

pp. 279-280 ◽

Cited By ~ 4

Author(s):

Jagannadha Avasarala

Keyword(s):

Multiple Sclerosis ◽

Clinical Studies ◽

Phase 3 ◽

The Past ◽

Caucasian Patients ◽

Approved Drugs ◽

Multiple Drugs ◽

Fda Approved Drugs

Pharmacotherapy of multiple sclerosis (MS) is evolving rapidly. Despite impressive gains over the past 2 decades in the approval of multiple drugs for MS, lack of recruitment of minorities with MS in phase 3 clinical studies is a persistent concern and skews efficacy and disability data.

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Attacking COVID-19 Progression Using Multi-Drug Therapy for Synergetic Target Engagement

Biomolecules ◽

10.3390/biom11060787 ◽

2021 ◽

Vol 11 (6) ◽

pp. 787

Author(s):

Mathew A. Coban ◽

Juliet Morrison ◽

Sushila Maharjan ◽

David Hyram Hernandez Medina ◽

Wanlu Li ◽

...

Keyword(s):

Model Systems ◽

Host Protein ◽

Drug Candidates ◽

The Past ◽

Computational Dynamics ◽

Structure Simulation ◽

Drug Pipeline ◽

Approved Drugs ◽

Fda Approved Drugs ◽

Fragment Libraries

COVID-19 is a devastating respiratory and inflammatory illness caused by a new coronavirus that is rapidly spreading throughout the human population. Over the past 12 months, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, has already infected over 160 million (>20% located in United States) and killed more than 3.3 million people around the world (>20% deaths in USA). As we face one of the most challenging times in our recent history, there is an urgent need to identify drug candidates that can attack SARS-CoV-2 on multiple fronts. We have therefore initiated a computational dynamics drug pipeline using molecular modeling, structure simulation, docking and machine learning models to predict the inhibitory activity of several million compounds against two essential SARS-CoV-2 viral proteins and their host protein interactors—S/Ace2, Tmprss2, Cathepsins L and K, and Mpro—to prevent binding, membrane fusion and replication of the virus, respectively. All together, we generated an ensemble of structural conformations that increase high-quality docking outcomes to screen over >6 million compounds including all FDA-approved drugs, drugs under clinical trial (>3000) and an additional >30 million selected chemotypes from fragment libraries. Our results yielded an initial set of 350 high-value compounds from both new and FDA-approved compounds that can now be tested experimentally in appropriate biological model systems. We anticipate that our results will initiate screening campaigns and accelerate the discovery of COVID-19 treatments.

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Multi-Targeted Approaches and Drug Repurposing Reveal Possible SARS-CoV-2 Inhibitors

Vaccines ◽

10.3390/vaccines10010024 ◽

2021 ◽

Vol 10 (1) ◽

pp. 24

Author(s):

Khalid Mashay Alanazi ◽

Mohammad Abul Farah ◽

Yan-Yan Hor

Keyword(s):

Experimental Validation ◽

Computational Analysis ◽

Treatment Options ◽

Drug Repurposing ◽

Binding Affinities ◽

Normal Model ◽

Inhibitory Potential ◽

Us Fda ◽

Approved Drugs ◽

Fda Approved Drugs

The COVID-19 pandemic caused by SARS-CoV-2 is unprecedented in recent memory owing to the non-stop escalation in number of infections and deaths in almost every country of the world. The lack of treatment options further worsens the scenario, thereby necessitating the exploration of already existing US FDA-approved drugs for their effectiveness against COVID-19. In the present study, we have performed virtual screening of nutraceuticals available from DrugBank against 14 SARS-CoV-2 proteins. Molecular docking identified several inhibitors, two of which, rutin and NADH, displayed strong binding affinities and inhibitory potential against SARS-CoV-2 proteins. Further normal model-based simulations were performed to gain insights into the conformational transitions in proteins induced by the drugs. The computational analysis in the present study paves the way for experimental validation and development of multi-target guided inhibitors to fight COVID-19.

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Recognizing drug targets using evolutionary information: implications for repurposing FDA-approved drugs against Mycobacterium tuberculosis H37Rv

Molecular BioSystems ◽

10.1039/c5mb00476d ◽

2015 ◽

Vol 11 (12) ◽

pp. 3316-3331 ◽

Cited By ~ 11

Author(s):

Gayatri Ramakrishnan ◽

Nagasuma R. Chandra ◽

Narayanaswamy Srinivasan

Keyword(s):

Mycobacterium Tuberculosis ◽

Drug Targets ◽

Drug Repurposing ◽

Target Space ◽

Evolutionary Information ◽

Mycobacterium Tuberculosis H37rv ◽

The Past ◽

Approved Drugs ◽

Fda Approved Drugs ◽

Computational Drug Discovery

Drug repurposing to explore target space has been gaining pace over the past decade with the upsurge in the use of systematic approaches for computational drug discovery.

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