Insights into newly approved drugs from a medicinal chemistry perspective

2021 ◽  
Vol 21 ◽  
Author(s):  
Elys Juliane Cardoso Lima ◽  
Renan Augusto Gomes ◽  
Evelin Fornari ◽  
Flavio da Silva Emery ◽  
Gustavo Henrique Goulart Trossini
Keyword(s):  
Drug Design ◽  
Drug Development ◽  
Drug Administration ◽  
Medicinal Chemistry ◽  
Food And Drug Administration ◽  
New Drugs ◽  
Design And Optimization ◽  
Continuous Evolution ◽  
Development Pipeline ◽  
Approved Drugs

: The development of new drugs is becoming notably harder each decade. To overcome the present pitfalls in the drug development pipeline, such as those related to potency, selectivity, or absorption, distribution, metabolism, excretion and toxicity properties, medicinal chemistry strategies need to be in continuous evolution and need to become even more multidisciplinary. In this review, we present how structure-based, ligand-based, and fragment-based drug design (SBDD, LBDD, and FBDD, respectively) and their respective techniques were used for the design and optimization of successful cases of new molecular entities (NMEs) approved by the Food and Drug Administration (FDA).

scholarly journals A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2020

2021 ◽  
Author(s):  
Gizem Kayki-Mutlu ◽  
Martin C. Michel
Keyword(s):  
Small Molecules ◽  
Drug Administration ◽  
Antisense Oligonucleotides ◽  
Food And Drug Administration ◽  
New Drugs ◽  
Small Interfering Rnas ◽  
Drug Discovery And Development ◽  
The Past ◽  
The Us ◽  
Approved Drugs

AbstractWhile the COVID-19 pandemic also affected the work of regulatory authorities, the US Food and Drug Administration approved a total of 53 new drugs in 2020, one of the highest numbers in the past decades. Most newly approved drugs related to oncology (34%) and neurology (15%). We discuss these new drugs by level of innovation they provide, i.e., first to treat a condition, first using a novel mechanisms of action, and “others.” Six drugs were first in indication, 15 first using a novel mechanism of action, and 32 other. This includes many drugs for the treatment of orphan indications and some for the treatment of tropical diseases previously neglected for commercial reasons. Small molecules continue to dominate new drug approvals, followed by antibodies. Of note, newly approved drugs also included small-interfering RNAs and antisense oligonucleotides. These data show that the trend for declines in drug discovery and development has clearly been broken.

Multicenter Analysis of Genomically Targeted Single Patient Use Requests for Pediatric Neoplasms

2021 ◽  
Author(s):  
Himalee S. Sabnis ◽  
David S. Shulman ◽  
Benjamin Mizukawa ◽  
Nancy Bouvier ◽  
Ahmet Zehir ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Drug Administration ◽  
Pediatric Cancer ◽  
Drug Targets ◽  
De Novo ◽  
Food And Drug Administration ◽  
Hematologic Malignancies ◽  
New Drugs ◽  
Single Patient ◽  
Patient Use

PURPOSE The US Food and Drug Administration–expanded access program (EAP) uses a single patient use (SPU) mechanism to provide patient access to investigational agents in situations where no satisfactory or comparable therapy is available. Genomic profiling of de novo and relapsed or refractory childhood cancer has led to increased identification of new drug targets in the last decade. The aim of this study is to examine the SPU experience for genomically targeted therapies in patients with pediatric cancer. PATIENTS AND METHODS All genomically targeted therapeutic SPUs obtained over a 5-year period were evaluated at four large pediatric cancer programs. Data were collected on the type of neoplasm, agents requested, corresponding molecularly informed targets, and clinical outcomes. RESULTS A total of 45 SPUs in 44 patients were identified. Requests were predominantly made for CNS and solid tumors (84.4%) compared with hematologic malignancies (15.6%). Lack of an available clinical trial was the main reason for SPU initiation (64.4%). The median time from US Food and Drug Administration submission to approval was 3 days (range, 0-12 days) and from Institutional Review Board submission to approval was 5 days (range, 0-50 days). Objective tumor response was seen in 39.5% (15 of 38) of all evaluable SPUs. Disease progression was the primary reason for discontinuation of drug (66.7%) followed by toxicity (13.3%). CONCLUSION SPU requests remain an important mechanism for pediatric access to genomically targeted agents given the limited availability of targeted clinical trials for children with high-risk neoplasms. Furthermore, this subset of SPUs resulted in a substantial number of objective tumor responses. The development of a multi-institutional data registry of SPUs may enable systematic review of toxicity and clinical outcomes and provide evidence-based access to new drugs in rare pediatric cancers.

An Introduction to the Basic Concepts in QSAR-Aided Drug Design

2015 ◽  
pp. 1-47 ◽  
Author(s):  
Maryam Hamzeh-Mivehroud ◽  
Babak Sokouti ◽  
Siavoush Dastmalchi
Keyword(s):  
Drug Design ◽  
Drug Development ◽  
Biological Activities ◽  
Model Development ◽  
Quantitative Structure Activity Relationship ◽  
Molecular Structures ◽  
New Drugs ◽  
Qsar Modeling ◽  
Qsar Studies ◽  
Modern Drug

The need for the development of new drugs to combat existing and newly identified conditions is unavoidable. One of the important tools used in the advanced drug development pipeline is computer-aided drug design. Traditionally, to find a drug many ligands were synthesized and evaluated for their effectiveness using suitable bioassays and if all other drug-likeness features were met, the candidate(s) would possibly reach the market. Although this approach is still in use in advanced format, computational methods are an indispensable component of modern drug development projects. One of the methods used from very early days of rationalizing the drug design approaches is Quantitative Structure-Activity Relationship (QSAR). This chapter overviews QSAR modeling steps by introducing molecular descriptors, mathematical model development for relating biological activities to molecular structures, and model validation. At the end, several successful cases where QSAR studies were used extensively are presented.

An Introduction to the Basic Concepts in QSAR-Aided Drug Design

Oncology ◽  
2017 ◽  
pp. 20-66
Author(s):  
Maryam Hamzeh-Mivehroud ◽  
Babak Sokouti ◽  
Siavoush Dastmalchi
Keyword(s):  
Drug Design ◽  
Drug Development ◽  
Biological Activities ◽  
Model Development ◽  
Quantitative Structure Activity Relationship ◽  
Molecular Structures ◽  
New Drugs ◽  
Qsar Modeling ◽  
Qsar Studies ◽  
Modern Drug

The need for the development of new drugs to combat existing and newly identified conditions is unavoidable. One of the important tools used in the advanced drug development pipeline is computer-aided drug design. Traditionally, to find a drug many ligands were synthesized and evaluated for their effectiveness using suitable bioassays and if all other drug-likeness features were met, the candidate(s) would possibly reach the market. Although this approach is still in use in advanced format, computational methods are an indispensable component of modern drug development projects. One of the methods used from very early days of rationalizing the drug design approaches is Quantitative Structure-Activity Relationship (QSAR). This chapter overviews QSAR modeling steps by introducing molecular descriptors, mathematical model development for relating biological activities to molecular structures, and model validation. At the end, several successful cases where QSAR studies were used extensively are presented.

Regulatory Perspectives: One Academic Viewpoint From the United States

2003 ◽  
Vol 15 (S1) ◽  
pp. 277-281
Author(s):  
Peter Whitehouse
Keyword(s):  
United States ◽  
Cognitive Impairment ◽  
Vascular Dementia ◽  
Drug Administration ◽  
Food And Drug Administration ◽  
The United States ◽  
New Drugs ◽  
Vascular Pathology ◽  
Vascular Burden ◽  
The Brain

The development of new drugs to treat vascular dementia and other conditions in which cognitive impairment is due at least in part to vascular pathology will require future interaction among academic, industry, and government regulatory clinicians and scientists. This article offers the author's perspective on the positive involvement of the Food and Drug Administration in development of conceptual frameworks and practical approaches to treatment of conditions characterized by vascular burden of the brain.

Enrollment of Elderly Patients in Clinical Trials for Cancer Drug Registration: A 7-Year Experience by the US Food and Drug Administration

2004 ◽  
Vol 22 (22) ◽  
pp. 4626-4631 ◽  
Author(s):  
Lilia Talarico ◽  
Gang Chen ◽  
Richard Pazdur
Keyword(s):  
Clinical Trials ◽  
Cancer Patients ◽  
Drug Administration ◽  
Food And Drug Administration ◽  
The Elderly ◽  
New Drugs ◽  
Cancer Drug ◽  
Cancer Therapies ◽  
Age Related ◽  
The Us

Purpose To analyze the age-related enrollment of cancer patients onto registration trials of new drugs or new indications approved by the US Food and Drug Administration from 1995 to 2002. Patients and Methods This study involved retrospective analyses of demographic data of cancer patients enrolled onto registration trials. The data on 28,766 cancer patients from 55 registration trials were analyzed according to age distributions of ≥ 65, ≥ 70, and ≥ 75 years. The rates of enrollment in each age group for each cancer were compared with the corresponding rates in the US cancer population. The age distributions of the US cancer population were derived from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute for the period 1995 to 1999 based on the 2000 US Census. Results The proportions of the overall patient populations aged ≥ 65, ≥ 70, and ≥ 75 years were 36%, 20%, and 9% compared with 60%, 46%, and 31%, respectively, in the US cancer population. Statistically significant under-representation of the elderly (P < .001) was noted in registration trials for all cancer treatment except for breast cancer hormonal therapies. Patients aged ≥ 70 years accounted for most of the under-representation. Conclusion Elderly were under-represented in the registration trials of new cancer therapies. Various strategies may be needed to evaluate cancer therapies for the elderly in prospective clinical trials and to improve cancer care in the elderly population.

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