AI-assisted synthesis prediction
Publication date: Available online 11 July 2020Source: Drug Discovery Today: TechnologiesAuthor(s): Simon Johansson, Amol Thakkar, Thierry Kogej, Esben Bjerrum, Samuel Genheden, Tomas Bastys, Christos Kannas, Alexander Schliep, Hongming Chen, Ola Engkvist (Source: Drug Discovery Today: Technologies)
Source: Drug Discovery Today: Technologies - July 12, 2020 Category: Drugs & Pharmacology Source Type: research
The art of atom descriptor design
Publication date: Available online 3 July 2020Source: Drug Discovery Today: TechnologiesAuthor(s): Andreas H. Göller (Source: Drug Discovery Today: Technologies)
Source: Drug Discovery Today: Technologies - July 4, 2020 Category: Drugs & Pharmacology Source Type: research
Molecular property prediction: recent trends in the era of artificial intelligence
Publication date: Available online 1 July 2020Source: Drug Discovery Today: TechnologiesAuthor(s): Jie Shen, Christos A. Nicolaou (Source: Drug Discovery Today: Technologies)
Source: Drug Discovery Today: Technologies - July 2, 2020 Category: Drugs & Pharmacology Source Type: research
Generative topographic mapping in drug design
Publication date: Available online 30 June 2020Source: Drug Discovery Today: TechnologiesAuthor(s): Dragos Horvath, Gilles Marcou, Alexandre Varnek (Source: Drug Discovery Today: Technologies)
Source: Drug Discovery Today: Technologies - July 1, 2020 Category: Drugs & Pharmacology Source Type: research
Organometallic compounds in drug discovery: Past, present and future
Publication date: Available online 27 June 2019Source: Drug Discovery Today: TechnologiesAuthor(s): Yih Ching Ong, Gilles GasserIn this review, we present an overview of some of the medicinally-relevant organometallic drugs that have been used in the past or that are currently in clinical trials as well as an example of compounds that are currently in the initial stage of drug development. Three main classes of organometallic complexes have been chosen for discussion: antimicrobial organoarsenicals, antimalarial and anticancer ferrocene-containing compounds and anticancer catalytic organometallic complexes. The purpose of ...
Source: Drug Discovery Today: Technologies - June 28, 2019 Category: Drugs & Pharmacology Source Type: research
Protein degradation for drug discovery
Publication date: April 2019Source: Drug Discovery Today: Technologies, Volume 31Author(s): Alessio Ciulli, William Farnaby (Source: Drug Discovery Today: Technologies)
Source: Drug Discovery Today: Technologies - June 12, 2019 Category: Drugs & Pharmacology Source Type: research
Small-molecule PROTAC degraders of the Bromodomain and Extra Terminal (BET) proteins — A review
Publication date: Available online 1 May 2019Source: Drug Discovery Today: TechnologiesAuthor(s): Chao-Yie Yang, Chong Qin, Longchuan Bai, Shaomeng WangThe PROteolysis TArgeting Chimeric (PROTAC) concept has provided an opportunity for the discovery and development of a completely new type of therapy involving induction of protein degradation. The BET proteins, comprised of BRD2, BRD3, BRD4 and the testis-specific BRDT protein, are epigenetic readers and master transcription coactivators. Extremely potent and efficacious small-molecule PROTAC degraders of the BET proteins, based on available, potent and selective BET inhib...
Source: Drug Discovery Today: Technologies - May 2, 2019 Category: Drugs & Pharmacology Source Type: research
Structurally-defined deubiquitinase inhibitors provide opportunities to investigate disease mechanisms
Publication date: Available online 1 April 2019Source: Drug Discovery Today: TechnologiesAuthor(s): Ingrid E. Wertz, Jeremy M. MurrayThe Ubiquitin/Proteasome System comprises an essential cellular mechanism for regulated protein degradation. Ubiquitination may also promote the assembly of protein complexes that initiate intracellular signaling cascades. Thus, proper regulation of substrate protein ubiquitination is essential for maintaining normal cellular physiology. Deubiquitinases are the class of enzymes responsible for removing ubiquitin modifications from target proteins and have been implicated in regulating human d...
Source: Drug Discovery Today: Technologies - April 3, 2019 Category: Drugs & Pharmacology Source Type: research
Targeted protein degradation in vivo with Proteolysis Targeting Chimeras: Current status and future considerations
Publication date: Available online 23 March 2019Source: Drug Discovery Today: TechnologiesAuthor(s): Gillian F. Watt, Paul Scott-Stevens, Lu GaohuaProteolysis Targeting Chimeras (PROTACs) are a rapidly expanding new therapeutic modality inducing selective protein degradation and offering the potential of a differentiated pharmacological profile across multiple therapeutic areas. As the repertoire of protein targets and E3 ligases available for incorporation into PROTACs continues to grow, understanding the drug- and system-dependent parameters for PROTACs will be critical for achieving tissue/cell specific pharmacology. Th...
Source: Drug Discovery Today: Technologies - March 23, 2019 Category: Drugs & Pharmacology Source Type: research
Cereblon modulators: Low molecular weight inducers of protein degradation
Publication date: Available online 13 March 2019Source: Drug Discovery Today: TechnologiesAuthor(s): Philip P. Chamberlain, Brian E. CathersTargeted protein degradation has become an exciting new paradigm in drug discovery with the potential to target new protein families for therapeutic intervention. In 2010, Hiroshi Handa and colleagues discovered that the drug thalidomide binds to the protein cereblon, a component of the CRL4CRBN E3 ubiquitin ligase. In contrast to the heterobifunctional small molecule degraders reported in the literature, thalidomide is of very low molecular weight (∼258Da) with molecular properties ...
Source: Drug Discovery Today: Technologies - March 14, 2019 Category: Drugs & Pharmacology Source Type: research
A critical evaluation of the approaches to targeted protein degradation for drug discovery
Publication date: Available online 6 March 2019Source: Drug Discovery Today: TechnologiesAuthor(s): Rajesh Chopra, Amine Sadok, Ian CollinsThere is a great deal of excitement around the concept of targeting proteins for degradation as an alternative to conventional inhibitory small molecules and antibodies. Protein degradation can be undertaken by bifunctional molecules that bind the target for ubiquitin mediated degradation by complexing them with Cereblon (CRBN), von Hippel-Lindau or other E-3 ligases. Alternatively, E-3 ligase receptors such as CRBN or DCAF15 can also be used as a ‘template’ to bind IMiD or sulphona...
Source: Drug Discovery Today: Technologies - March 7, 2019 Category: Drugs & Pharmacology Source Type: research
Advanced proteomics approaches to unravel protein homeostasis
Publication date: Available online 23 February 2019Source: Drug Discovery Today: TechnologiesAuthor(s): Paola Grandi, Marcus BantscheffQuantitative proteomics methods are instrumental in measuring the interplay between protein synthesis and protein degradation in cells and tissues in different conditions and substantially contribute to the understanding of control mechanisms for protein homeostasis. Proteomics and chemoproteomics approaches enable the characterization of small molecule modifiers of protein degradation for therapeutic applications. Here, we review recent developments and applications of mass spectrometry-ba...
Source: Drug Discovery Today: Technologies - February 25, 2019 Category: Drugs & Pharmacology Source Type: research
PROteolysis TArgeting Chimeras (PROTACs) — Past, present and future
Publication date: Available online 13 February 2019Source: Drug Discovery Today: TechnologiesAuthor(s): Mariell Pettersson, Craig M. CrewsThe majority of currently used therapeutics are small molecule-based and utilize occupancy-driven pharmacology as the mode of action (MOA), in which the protein function is modulated via temporary inhibition. New modalities that operate using alternative MOAs are essential for tapping into the “undruggable” proteome. The PROteolysis Targeting Chimera (PROTAC) technology provides an attractive new approach that utilizes an event-driven MOA. Small molecule-based heterobifunctional PROT...
Source: Drug Discovery Today: Technologies - February 13, 2019 Category: Drugs & Pharmacology Source Type: research
Targeted protein degradation mechanisms
Publication date: Available online 28 January 2019Source: Drug Discovery Today: TechnologiesAuthor(s): Yi Zhang, Christine Loh, Jesse Chen, Nello MainolfiTargeted protein degradation mediated by small molecule degraders represents an exciting new therapeutic opportunity to eliminate disease-causing proteins. These molecules recruit E3 ubiquitin ligases to the protein of interest and mediate its ubiquitination and subsequent proteolysis by the proteasome. Significant advancements have been made in the discovery and development of clinically relevant degraders. In this review we will focus on the recent progress in understan...
Source: Drug Discovery Today: Technologies - January 29, 2019 Category: Drugs & Pharmacology Source Type: research
SNIPERs—Hijacking IAP activity to induce protein degradation
Publication date: Available online 14 January 2019Source: Drug Discovery Today: TechnologiesAuthor(s): Mikihiko Naito, Nobumichi Ohoka, Norihito ShibataAbstractThe induction of protein degradation by chimeric small molecules represented by proteolysis-targeting chimeras (PROTACs) is an emerging approach for novel drug development. We have developed a series of chimeric molecules termed specific and non-genetic inhibitor of apoptosis protein (IAP)-dependent protein erasers (SNIPERs) that recruit IAP ubiquitin ligases to effect targeted degradation. Unlike the chimeric molecules that recruit von Hippel–Lindau and cereblon ...
Source: Drug Discovery Today: Technologies - January 15, 2019 Category: Drugs & Pharmacology Source Type: research
