Drug Hunter’s Post

Interesting talk to follow

Maryam Sadeghi and  Bahram Khoshnevisan in their study they have explored on density functional theory to model a drug delivery system with Ti C MXene as a carrier and 5-fluorouracil as a selected drug molecule. The electronic, magnetic and structural properties were calculated during the procedure. The results show that the Ti C surface is very favorable for the adsorption of drugs. Magnetic hyperthermia and drug delivery are dependent on the magnetization of Ti C after FU adsorption. Our calculations show that in the slightly acidic environment of tumor tissue, FU could start to be released by increasing distance from the MXene surface and then instability of the complex, without any significant change in the structural properties. An important contribution to the discovery and application of novel 2D materials as drug delivery systems could be provided by this study. #MXenenanosheets #Drugdeliverysystem #Computationalchemistry https://lnkd.in/gMvQgHVG

Read this paper! This excellent paper by Kim et. al. describes studies on morphologically-directed Raman spectroscopy as an analytical method for subvisible particle characterization in therapeutic protein product quality. Quoting from the abstract: "Subvisible particles (SVPs) are a critical quality attribute of injectable therapeutic proteins (TPs) that needs to be controlled due to potential risks associated with drug product quality. The current compendial methods routinely used to analyze SVPs for lot release provide information on particle size and count. However, chemical identification of individual particles is also important to address root-cause analysis. Herein, we introduce Morphologically-Directed Raman Spectroscopy (MDRS) for SVP characterization of TPs. The following particles were used for method development: (1) polystyrene microspheres, a traditional standard used in industry; (2) photolithographic (SU-8); and (3) ethylene tetrafluoroethylene (ETFE) particles, candidate reference materials developed by NIST. In our study, MDRS rendered high-resolution images for the ETFE particles (> 90%) ranging from 19 to 100 μm in size, covering most of SVP range, and generated comparable morphology data to flow imaging microscopy. Our method was applied to characterize particles formed in stressed TPs and was able to chemically identify individual particles using Raman spectroscopy. MDRS was able to compare morphology and transparency properties of proteinaceous particles with reference materials. The data suggests MDRS may complement the current TPs SVP analysis system and product quality characterization workflow throughout development and commercial lifecycle."

Tandem mass spectrometry (tandem MS, or MS/MS) has been in use for several decades for the accurate identification of molecules. Compositional identification of molecules by tandem MS is frequently accomplished by breaking the precursor molecules into substituent components via collisional activation at kinetic energies of < 200 electron volts (eV), a process generally referred to as collision-induced dissociation (CID). TOF-SIMS tandem MS imaging has been particularly useful in a broad range of applications including single cell-omics, #metabolomics, natural product chemistry, #pharmaceutical research, high-performance #polymers and composites, 2D materials, electronic devices, #catalysis, #forensics, and failure analysis. Learn more: https://lnkd.in/gu_KGK3n For more information on how surface analysis is exploring the advantages of surface-induced dissociation (SID) to aid in molecular identification alongside CID spectra., please attend the upcoming SIMS Europe 2023 https://lnkd.in/ggHBySQj where Dr. Gregory L. Fisher is invited to give a talk on "The Utility of Surface-Induced Dissociation in Molecular Identification." #innovation #tof-sims #conference #tandem #uk #chemistry #failureanalysis

Great blog clearly explaining how crystal structures can help in drug discovery and development!

Outsourcing computational chemistry can play an important role in maximising your R&D outcome.   Computational chemistry, CADD, and cheminformatics applications are key components of any science-led drug discovery project. They are applied at all stages of the drug discovery process to impact projects and move compounds towards the clinic. As an integrated drug discovery CRO, BioAscent's scientists can support each key stage of the drug discovery process.   Find out more about our in silico and data analysis expertise here: https://lnkd.in/dBQqiBvQ   #InSilico #DrugDiscovery #IntegratedDrugDiscovery #DrugDesign #InSilicoDiscovery #CompChem #ComputationalChemistry #CADD

Scientists have generated a new method for the #de_novo_design of drug (#small_molecules)-binding proteins with predictable binding energy and specificity. They screened three top-scoring designs and identified one that bound to the desired small molecule with subnanomolar affinity even without laborious optimization. Experimental validation and computational work confirmed the design accuracy and revealed a correlation between predicted and observed binding affinity for related drug molecules. https://lnkd.in/ebANkgp4

NMR as a gold standard for drug design. With key words „nmr“ and „drug design“, this is what the authors found in Scopus: an eye on global research. The number of scientific reports keeps increasing over the years, witnessing of the continuous relevance of NMR for drug design. The number of patents for the same two key words is declining. Is it a bad sign? Not necessarily, it also means that NMR starts to become a standardized tool and it is used as such. The end game is discovering new chemical matters not associating it systematically with a novel methodology. Image from article: https://lnkd.in/ew9CJHJ8

My feeling is that the decline of applications for patents is a universal tendency. I have authored 3 patents but they only cost me money; I stopped keeping them alive and they are now expired. Patenting still survives in pharma (they once patented even the DNA of their grandmothers 😀) but even there it is dropping. Originally (XIX century) patents were only awarded to "discoverers" who had to present a patentable prototype. But more recently nobody ever presents any axtual device, and even would-be "methods" are accepted. The problem is that as instances of both categories become ever more complex (think of electronic boards or of DNP in NMR) it is ever more easier to claim (correctly or falsely) that a minor modification is an improvement of an original patent and therefore itself patentable. Not to speak about ridiculous pseudo-patents that basically just re-invent hot water. And in many cases patents are currently used as a referee-less substitute for citable publication. As far as I see it, patenting is dead, except in a few shrinking enclaves (such as potato peelers). The US Patent office itself has statistics showing that only less than 1% of registered patents actually make enough profit to cover the patent costs. Think twice before patenting anything!

SKELETAL EDITING AS A NEW APPROACH IN DRUG DISCOVERY A new toolbox in organic synthesis, skeletal editing enables deletion or insertion of single atoms in an existing molecule. Often the conditions are mild and protocols have only limited steps. Already, it is impacting drug discovery as it is akin to use of a surgical knife or a molecular tweezer to achieve precise structural remodelling. Apart from drug discovery, it is also finding application in material science; an example is designing polythene which is more easily degradable by inserting vulnerable bonds. #drugdiscovery #organicsynthesis #materialsscience #chemistry #pharmaceuticalindustry