Showing papers in "Drug Discovery Today: Technologies in 2018"

TL;DR: HDP-101 is an Amanitin based ADC directed against BCMA and will be advancing to the clinical phase in 2019, supporting the clinical development of amanitin-based ADCs by using a toxin with a new mode of action and with a favorable therapeutic index.

TL;DR: The Povarov multicomponent reaction consists on the condensation of an aniline, an aldehyde, and an activated olefin to generate a tetrahydroquinoline adduct with 3 diversity points and its uses in medicinal chemistry are reported.

TL;DR: Through addressing challenges that still remain in bringing these complex formulations to the clinic, ACNPs hold obvious potential for the treatment of a wide range of cancers and other diseases where selective targeting of drug agents is essential.

TL;DR: An overview on methods that attempt to increase the safety and efficacy of ADCs via "self-hydrolysing maleimides" or by improving the stability of maleimide-conjugates by other means is provided.

TL;DR: The generation, modification, and application of emerging antibody fragments and synthetic antibody mimics are summarized, with a focus on their use as drug carriers.

TL;DR: A survey of site-specific chelator-protein conjugation methods can be found in this article, with a focus on enzyme-mediated chelator conjugations and sequences of amino acids that chelate the radiometal.

TL;DR: The antibody-drug conjugate (ADC) field has seen a remarkable expansion in the number of entrants in clinical studies, and many of these technologies are now competing head-to-head by targeting the same antigen in similar patient populations, allowing for a direct comparison of their clinical performance properties.

TL;DR: An extensive overview of these new CRISPR/Cas9-mediated disease models that can provide both cost-effective genotype-phenotype correlations for gene-(variants) and genomic rearrangements obtained from clinical practice, as well as be exploited to perform translational research to improve prospects of disease afflicted patients are shown.

TL;DR: Main drug release mechanisms are detailed and reviewed to support rational design in pharmaceutical technology and manufacturing considering the fact that R&D members of the industry are forced to obtain knowledge about excipients and methods pros and cons.

TL;DR: The 3 main reagent classes which have been exemplified for the construction of ADCs by disulfide bridging will be discussed in this review; bissulfones, next generation maleimides and pyridazinediones, along with others in development.

TL;DR: This minireview will explore the potential synergies that can exist between monospecific antibody therapeutics development such as antibody-drug conjugates (ADCs) and protein conjugation and cytotoxicity.

TL;DR: The correlation between the physicochemical parameters and the behavior of self-emulsifying drug delivery systems was established and these physicochemical factors characterized SEDDS were summarized.

TL;DR: The current status of the most widely used automated assays for thermodynamic solubility are discussed, followed by recent high throughput measurements of properties related tosolubility (e.g. dissolution rate and supersaturation), and a brief overview of predictive computational Methods reported in the literature are discussed.

TL;DR: This paper uses the Block Relevance (BR) analysis to theoretically show how log Poct is not a convenient choice to assess IMHB properties of candidates and introduces Δlog Poct-tol, i.e. the difference between log PoCT and log Ptol (the logarithm of the partition coefficient in the toluene/water system).

TL;DR: Recent advances in the use of hPSC-CMs and CRISPR/Cas9-mediated genome editing to study cardiotoxicity and model CVD are reviewed.

TL;DR: This review focuses on nasal and pulmonary delivery of NSAIDs for fast-onset analgesia, for the potential prevention of Alzheimer's disease, as well as for an add-on treatment in cystic fibrosis and non-small cell lung cancer.

TL;DR: PKa calculations are reliable enough that they can be used to filter out high-energy tautomers from databases used for virtual screening, and continuous improvements in both pKa prediction software and theoretical calculations promise further improvements in solving the challenges of tautomerize.

TL;DR: Of those in clinical trials systemic toxicities are beginning to emerge, observed toxicities in relation to the structures and mechanisms of action of payload type are discussed.

TL;DR: This account summarizes recent developments of aggregation-induced emissive and emission solvatochromic fluorophores by multicomponent reactions and key intermediates are catalytically generated alkynoyl derivatives that are directly transformed into luminophores in a one-pot fashion.

TL;DR: At present, various (chemo)enzymatic approaches for site-specific and stable conjugation of toxic payloads are making their way to the clinic, thereby potentially providing ADCs with increased therapeutic window.

TL;DR: This work states that miniaturized high throughput assays coupled to analytical techniques such as solid-state characterization, ultra performance liquid chromatography, or polychromatic turbidimetry, have been developed, thereby enabling a more complex physicochemical profiling at the early discovery stage.

TL;DR: Miniaturised ADCs, chemically-modified with ultra-potent cytotoxic payloads offer an alternative approach for oncology therapeutics, promising a wider therapeutic window by virtue of superior solid tumour penetration properties and more rapid system clearance.

TL;DR: Drug discovery programs that generate hundreds of new molecular entities need efficient methodologies for physicochemical profiling and potentiometric and UV-metric-based methods find their place as very precise methods for pKa determination despite of somewhat lower throughput.

TL;DR: This review will discuss the methods used to prepare boron-containing molecules of biological relevance from multicomponent reactions with borylated building blocks.

TL;DR: Multicomponent reaction (MCR) chemistry is very well suited for the synthesis of a diverse range of macrocycles and is also able to generate great levels of molecular diversity and complexity at low synthetic costs.

TL;DR: A selection of recent variations on the Petasis three-component reaction theme for the synthesis of scaffolds of relevance to medicinal chemistry are presented.

TL;DR: If used for future therapies, CRISPR/Cas9 genome surgery could eliminate the need for patients with retinal diseases to undergo repetitive procedures such as drug injections, and the many ways in which researchers are currently utilizing this versatile tool are explored.

TL;DR: Achievements and current limitations of CRISPR/Cas9 genome editing in hematopoietic cells are discussed with special emphasis on its potential use in ex vivo gene therapy of monogenic blood disorders, HIV and cancer.

TL;DR: This review outlines the developments achieved in the past decade of post multicomponent reaction transformations, highlighting the modifications that are performed in a sequential or domino fashion with emphasis on major concepts, synthetic applications of the derived products as well as mechanistic aspects.