scholarly journals Improving the assessment of the probability of success in late stage drug development

2021 ◽  
Author(s):  
Lisa V. Hampson ◽  
Björn Bornkamp ◽  
Björn Holzhauer ◽  
Joseph Kahn ◽  
Markus R. Lange ◽  
...  
Keyword(s):  
Drug Development ◽  
Late Stage ◽  
Probability Of Success

Sequential C-Selective Difluoromethylation/Pd-Catalyzed Decarboxylative Protonation: An Efficient Access to Tertiary Difluoromethylated Scaffolds

2019 ◽  
Author(s):  
Nicolas Duchemin ◽  
Roberto Buccafusca ◽  
Marc Daumas ◽  
Vincent Ferey ◽  
Stellios Arseniyadis
Keyword(s):  
Drug Development ◽  
Late Stage ◽  
Efficient Access ◽  
Palladium Catalyzed ◽  
General Method

We report here a general method that allows a highly straightforward access to tertiary difluoromethylated compounds. The strategy relies on a two-step sequence featuring a C-selective electrophilic difluoromethylation and an unprecedented palladium-catalyzed decarboxylative protonation. Considering the generality of the method and the attractive properties offered by the difluoromethyl group, this approach provides a valuable tool for late-stage functionalization and drug development.<br>

Pharmacokinetic/Pharmacodynamic Modeling for Drug Development in Oncology

2017 ◽  
pp. 210-215 ◽  
Author(s):  
Elena Garralda ◽  
Rodrigo Dienstmann ◽  
Josep Tabernero
Keyword(s):  
Drug Development ◽  
Critical Issue ◽  
Pharmacodynamic Modeling ◽  
Attrition Rates ◽  
Drug Candidates ◽  
Probability Of Success ◽  
Disease Behavior ◽  
Oncology Drug Development ◽  
Proof Of Mechanism ◽  
Early Drug

High drug attrition rates remain a critical issue in oncology drug development. A series of steps during drug development must be addressed to better understand the pharmacokinetic (PK) and pharmacodynamic (PD) properties of novel agents and, thus, increase their probability of success. As available data continues to expand in both volume and complexity, comprehensive integration of PK and PD information into a robust mathematical model represents a very useful tool throughout all stages of drug development. During the discovery phase, PK/PD models can be used to identify and select the best drug candidates, which helps characterize the mechanism of action and disease behavior of a given drug, to predict clinical response in humans, and to facilitate a better understanding about the potential clinical relevance of preclinical efficacy data. During early drug development, PK/PD modeling can optimize the design of clinical trials, guide the dose and regimen that should be tested further, help evaluate proof of mechanism in humans, anticipate the effect in certain subpopulations, and better predict drug-drug interactions; all of these effects could lead to a more efficient drug development process. Because of certain peculiarities of immunotherapies, such as PK and PD characteristics, PK/PD modeling could be particularly relevant and thus have an important impact on decision making during the development of these agents.

Level of Risk Advocated by Alcoholics

1970 ◽  
Vol 27 (3) ◽  
pp. 829-830 ◽  
Author(s):  
Brendan Gail Rule ◽  
Dorothy Phillips Besier
Keyword(s):  
Analysis Of Variance ◽  
Late Stage ◽  
Item Questionnaire ◽  
Probability Of Success ◽  
Level Of Risk

12 male alcoholism counsellors and 12 male late stage alcoholic patients responded to a 5-item questionnaire consisting of 3 items chosen from the Wallach and Kogan Choice Dilemmas questionnaire and 2 items constructed to represent dilemmas concerning alcohol. Ss indicated the lowest probability of success they would accept to take the risky alternative, which was clearly the more desirable choice. Results of a 2 × 5 analysis of variance indicated that alcoholics were more conservative in the probabilities they would accept to take the risky alternative, than were the counsellors. Furthermore, the items differed significantly from each other.

Developing Novel Anticancer Drugs for Targeted Populations: An Update

2020 ◽  
Vol 26 ◽  
Author(s):  
Tadesse Bekele Tafesse ◽  
Mohammed Hussen Bule ◽  
Fazlullah Khan ◽  
Mohammad Abdollahi ◽  
Mohsen Amini
Keyword(s):  
Drug Discovery ◽  
Drug Development ◽  
Anticancer Drugs ◽  
Anticancer Drug ◽  
Development Process ◽  
De Novo ◽  
Drug Repurposing ◽  
Drug Discovery And Development ◽  
Probability Of Success ◽  
Selection Of

Background: Due to higher failure rates, lengthy time and high cost of the traditional de novo drug discovery and development process; the rate of opportunity to get new, safe and efficacious drugs for the targeted population including pediatric patients with cancer becomes sluggish. Objectives: This paper discusses the development of novel anticancer drugs focusing on the identification and selection of target anticancer drug development for the targeted population. Methods: Information presented in this review was obtained from different databases including PUBMED, SCOPUS, Web of Science, and EMBASE. Various keywords were used as search terms. Results: The pharmaceutical companies currently are executing drug repurposing as an alternative means to accelerate the drug development process that reduces the risk of failure, time and cost, which takes 3-12 years with almost 25% overall probability of success as compared to de novo drug discovery and development process (10-17 years) which has less than 10% probability of success. An alternative strategy to the traditional de novo drug discovery and development process, called drug repurposing, is also presented. Conclusion: Therefore, to continue with the progress of developing novel anticancer drugs towards the targeted population, identification and selection of the target to the specific disease type is important considering the aspects of the age of the patient and the disease stages such as each cancer types are different when we consider the disease at a molecular level. Drug repurposing technique becomes an influential alternative strategy to discover and develop novel anticancer drug candidates.

scholarly journals in silico ADMET Screening of Compounds Present in Cyanthillium cinereum (L.) H. Rob.

2020 ◽  
Vol 32 (6) ◽  
pp. 1421-1426
Author(s):  
J. Dharani ◽  
S. Ravi
Keyword(s):  
Drug Development ◽  
Late Stage ◽  
In Silico ◽  
Chemical Structure ◽  
Discovery Process ◽  
In Silico Admet

Drug development involves assessment of absorption, distribution, metabolism, excretion and toxicity (ADMET) increasingly earlier in the discovery process. in silico ADMET studies are expected to reduce the risk of late-stage attrition of drug development and to optimize screening and testing by looking at only the promising compounds. To this end, several in silico approaches for predicting ADMET properties of compounds from their chemical structure have been developed, ranging from data-based approaches. In this study, ADMET prediction has been done for 20 compounds from the plant Cyanthillium cinereum extracts. Some of the compounds were predicted to be non-toxic.

Sequential C-Selective Difluoromethylation/Pd-Catalyzed Decarboxylative Protonation: An Efficient Access to Tertiary Difluoromethylated Scaffolds

2019 ◽  
Author(s):  
Nicolas Duchemin ◽  
Roberto Buccafusca ◽  
Marc Daumas ◽  
Vincent Ferey ◽  
Stellios Arseniyadis
Keyword(s):  
Drug Development ◽  
Late Stage ◽  
Efficient Access ◽  
Palladium Catalyzed ◽  
General Method

We report here a general method that allows a highly straightforward access to tertiary difluoromethylated compounds. The strategy relies on a two-step sequence featuring a C-selective electrophilic difluoromethylation and an unprecedented palladium-catalyzed decarboxylative protonation. Considering the generality of the method and the attractive properties offered by the difluoromethyl group, this approach provides a valuable tool for late-stage functionalization and drug development.<br>

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