Abstract
The high attrition rate in drug development and the deteriorated drug ability as a result of the shifted chemical space of new therapeutic target for unmet medical needs have posed drastic challenges in current drug discovery. It has triggered the strategic transition in the past decade into parallel assessment of efficacy and comprehensive ADMET (absorption, distribution, metabolism, elimination and toxicity) properties of new chemical entities (NCEs) in the lead selection and optimization stages, to convert chemically a problematic NCE to an “all-around” candidate. This review summarizes multiple in silico, in vitro and in vivo ADMET filters developed and implemented in various stages of drug discovery to flag potential ADMET issues in the clinic. The full awareness of the benefits and limitations of each tool assures right questions to be answered using right tools at right time. The integrated ADMET risk assessment will allow project teams to have a clear vision in terms of the competitive position of own NCEs against comparable marketed drugs.
Keywords: ADMET, profiling, solubility, permeability, metabolism, drugability, absorption, bioavailability
Current Pharmaceutical Design
Title: Comprehensive Assessment of ADMET Risks in Drug Discovery
Volume: 15 Issue: 19
Author(s): Jianling Wang
Affiliation:
Keywords: ADMET, profiling, solubility, permeability, metabolism, drugability, absorption, bioavailability
Abstract: The high attrition rate in drug development and the deteriorated drug ability as a result of the shifted chemical space of new therapeutic target for unmet medical needs have posed drastic challenges in current drug discovery. It has triggered the strategic transition in the past decade into parallel assessment of efficacy and comprehensive ADMET (absorption, distribution, metabolism, elimination and toxicity) properties of new chemical entities (NCEs) in the lead selection and optimization stages, to convert chemically a problematic NCE to an “all-around” candidate. This review summarizes multiple in silico, in vitro and in vivo ADMET filters developed and implemented in various stages of drug discovery to flag potential ADMET issues in the clinic. The full awareness of the benefits and limitations of each tool assures right questions to be answered using right tools at right time. The integrated ADMET risk assessment will allow project teams to have a clear vision in terms of the competitive position of own NCEs against comparable marketed drugs.
Export Options
About this article
Cite this article as:
Wang Jianling, Comprehensive Assessment of ADMET Risks in Drug Discovery, Current Pharmaceutical Design 2009; 15 (19) . https://dx.doi.org/10.2174/138161209788682514
DOI https://dx.doi.org/10.2174/138161209788682514 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
The Promotional Effect of Mesenchymal Stem Cell Homing on Bone Tissue Regeneration
Current Stem Cell Research & Therapy Clinical Phenotypes of Severe Cutaneous Drug Hypersensitivity Reactions
Current Pharmaceutical Design New Approaches in the Management of Septic Shock
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents Vascular Inflammation in Cardiovascular Disease: Is Immune System Protective or Bystander?
Current Pharmaceutical Design Hypertension and Diabetes: Emphasis on the Renin-Angiotensin System in Atherosclerosis
Current Hypertension Reviews Therapeutical Approaches of Vasoactive Intestinal Peptide as a Pleiotropic Immunomodulator
Current Pharmaceutical Design Aquaporin-1 and Sodium-Hydrogen Exchangers as Pharmacological Targets in Diabetic Atherosclerosis
Current Drug Targets Preterm Birth, Inflammation and Infection: New Alternative Strategies for their Prevention
Current Pharmaceutical Biotechnology Preeclampsia: Placental Origins, New Predictors and New Therapeutic Strategies
Current Women`s Health Reviews Desensitization Protocol for Rituximab-Induced Serum Sickness
Current Drug Safety Leukocytoclastic Vasculitis Associated with HHV6-A/ciHHV6-A and HHV6-B Coinfection in an Immunocompetent Woman
Endocrine, Metabolic & Immune Disorders - Drug Targets Disease Modifying Approaches for Alzheimers Pathology
Current Pharmaceutical Design Renal Function, Albumin-Creatinine Ratio and Pulse Wave Velocity Predict Silent Coronary Artery Disease and Renal Outcome in Type 2 Diabetic and Prediabetic Subjects
Current Hypertension Reviews Imaging Subclinical Atherosclerosis: Where Do We Stand?
Current Cardiology Reviews Recent Understanding of Leukocytapheresis (LCAP) for the Treatment of Inflammatory Bowel Disease
Current Pharmaceutical Design New Insights into the Regulation of Liver Inflammation and Oxidative Stress
Mini-Reviews in Medicinal Chemistry Chest Pain in Children
Current Pediatric Reviews Editorial [Hot Topic:Active and Passive Aβ-Immunotherapy: Preclinical and Clinical Studies and Future Directions: Part I (Guest Editors: Michael G. Agadjanyan and David H. Cribbs)]
CNS & Neurological Disorders - Drug Targets Fibroblast Growth Factor-2 Antagonist and Antiangiogenic Activity of Long-Pentraxin 3-Derived Synthetic Peptides
Current Pharmaceutical Design Effectiveness of Long-Term Macrolide Therapy in Cryptogenic Organising Pneumonia
Current Respiratory Medicine Reviews