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
-
Update on Pharmacologic Retinal Vascular Toxicity
Current Pharmaceutical Design Biologics for the Treatment of Juvenile Idiopathic Arthritis
Current Medicinal Chemistry Central Nervous System Manifestations in Systemic Lupus Erythematosus
Current Rheumatology Reviews γ-Secretase-Regulated Signaling Typified by Notch Signaling in the Immune System
Current Stem Cell Research & Therapy PCSK9 and LDLR The Yin-Yang in the Cellular Uptake of Cholesterol
Current Hypertension Reviews The Role of Nuclear Receptor PPARα in the Sleep-wake Cycle Modulation. A Tentative Approach for Treatment of Sleep Disorders
Current Drug Delivery Utilizing Delta Opioid Receptors and Peptides for Cytoprotection: Implications in Stroke and Other Neurological Disorders
CNS & Neurological Disorders - Drug Targets Large Porous Hollow Particles: Lightweight Champions of Pulmonary Drug Delivery
Current Pharmaceutical Design Angiogenic Growth Factors in the Treatment of Peripheral Arterial Disease
Current Vascular Pharmacology Mouse Models of Experimental Autoimmune Uveitis: Comparative Analysis of Adjuvant-Induced vs Spontaneous Models of Uveitis
Current Molecular Medicine Features of Bioaccumulation and Toxic Effects of Copper (II) Oxide Nanoparticles Under Repeated Oral Exposure in Rats
Pharmaceutical Nanotechnology Natural Products and Cancer Stem Cells
Current Pharmaceutical Design Mapping Myeloperoxidase to Identify its Promiscuity Properties Using Docking and Molecular Dynamics Simulations
Current Pharmaceutical Design Covid-19 in Man: A Very Dangerous Affair
Endocrine, Metabolic & Immune Disorders - Drug Targets The Influence of Different Disease States on Rituximab Pharmacokinetics
Current Drug Metabolism Desensitization for Drug Hypersensitivity to Chemotherapy and Monoclonal Antibodies
Current Pharmaceutical Design Nanovehicle-based Small Interfering RNA (siRNA) Delivery for Therapeutic Purposes: A New Molecular Approach in Pharmacogenomics
Current Clinical Pharmacology Thalidomide as an Immunotherapeutic Agent: The Effects on Neutrophil- Mediated Inflammation
Current Pharmaceutical Design Use of Anti-Infective Drugs in Rheumatology
Anti-Infective Agents in Medicinal Chemistry Effects on Cytokines and Histology by Treatment with the Ace Inhibitor Captopril and the Antioxidant Retinoic Acid in the Monocrotaline Model of Experimentally Induced Lung Fibrosis
Current Pharmaceutical Design