#Oseltamivir aziridines are potent #influenza #neuraminidase #inhibitors and imaging agents

When the immune system detects a protein from a pathogen,
it’s supposed to dispatch killer T cells to eliminate the invader.

Some cancers can interfere with this process by hijacking the checkpoint proteins that keep our immune system from revving out of control
and using them to turn T cells off.

Starting in the mid-1990s, several research teams found success by treating mice with #checkpoint #inhibitors,
-- then a new class of drugs designed to keep tumor cells from concealing their identity and signaling, effectively, “nothing to see here.”

Thirty years on, checkpoint inhibitors have become a transformative tool in cancer treatment, especially for melanoma.

The research that went into developing checkpoint inhibitors showed conclusively that immune cells detect cancer much in the same way they identify other pathogens:

through differences in protein structure determined by DNA
—a crucial insight.

But as revolutionary as checkpoint inhibitors have been for immunotherapy, they don’t work for everyone
—far from it.

Some 80 percent of patients do not respond to this class of drugs.

Researchers are still trying to understand all the mechanisms that play a role in determining who does respond,
but one key factor is whether the immune system is able to recognize tumor cells on the basis of their mutations.

This is where mRNA vaccines come in.

#Jason #Luke, a melanoma researcher who now serves as chief medical officer of mRNA-medicine start-up #Strand #Therapeutics,
helped to design several ongoing clinical trials of mRNA vaccines for cancer.

He explains that both checkpoint inhibitors and mRNA vaccines build on our deep evolutionary adaptation for fighting pathogens
by identifying the proteins they shed in our bodies.

But checkpoint inhibitors are effective only if the patient’s immune system recognizes the cancer as a threat.

In contrast, mRNA vaccines have the potential to work even in patients whose cancers haven’t spurred much immune response.

The trick, Luke says, is using computational tools to decipher which of a given tumor’s mutations are most likely to be found by the immune system.

#MichaelMemoli
#WilliamColey #immunotherapy #stroma #MHC

#Global #update on susceptibilities of #influenza viruses to #neuraminidase #inhibitors and the cap-dependent endonuclease inhibitor #baloxavir, 2020–2023, https://etidiohnew.blogspot.com/2025/06/global-update-on-susceptibilities-of.html
#Global #update on susceptibilities of #influenza viruses to #neuraminidase #inhibitors and the cap-dependent endonuclease inhibitor #baloxavir, 2020–2023

Effects of #JAK #inhibitors in adults admitted to #hospital due to #COVID19: a systematic review and individual participant data meta-analysis of randomised clinical trials, https://etidiohnew.blogspot.com/2025/05/effects-of-jak-inhibitors-in-adults.html
Effects of #JAK #inhibitors in adults admitted to #hospital due to #COVID19: a systematic review and individual participant data meta-analysis of randomised clinical trials

SciTech Chronicles. . . . . .May 6th, 2025

https://bit.ly/stc050625

#EphB1/2 #tyrosine #kinase #inhibitors #carbene #thiamine #Breslow #B1 #3D-printable #electroencephalogram #continuously #bioadhesive #AMT #mesothelioma #"low-carbon metal oxides" #CO2 #"digital twin" #"3D digital model" #sonar #Magellan

SciTech Chronicles. . . . . . . . .May 6th, 2025

We are Volunteers of America. Vol II No 30 371 links Curated Mission Control RSS Feed Wordpress SubStack Comments Buy Me A Coffee New Mol...

Great keynote lecture by Marta Artola of the @LED3hub at #Lunteren. She talked about the importance of glycosidases in various diseases and her great work on conformationally locked #covalent and non-covalent #inhibitors and #probes.
#chemistry #ChemBio
https://pubs.acs.org/doi/10.1021/jacs.2c05666
Great keynote lecture by @martola.bsky.social of the @led3hub.bsky.social at #Lunteren. She talked about the importance of glycosidases in various diseases and her great work on conformationally locked #covalent and non-covalent #inhibitors and #probes. #chemsky #ChemBio pubs.acs.org/doi/10.1021/...
Artola Lab (@martola.bsky.social)

Bluesky Social
Plant Histone Deacetylases: Their Classification and Inhibitor Search - Cytology and Genetics

Abstract Histone deacetylases is a family of enzymes pivotal in regulating numerous crucial cellular processes in both plant and animal cells. Plant histone deacetylases have been considerably less investigated in comparison to their human counterparts. This study aims to provide an in-depth characterization of histone deacetylases in two model plant proteins-species Arabidopsis thaliana and Oryza sativa. Phylogenetic analysis of their relationship to known human homologs has revealed their close relation to three classes of human histone deacetylases. Notably, the highest sequence homology among histone deacetylases from different evolutionary origins was observed between human HDAC6 and A. thaliana HDA5 (43.6% homology). Structural alignment results highlighted the conservation of catalytic domains and demonstrated a high activity of inhibitors against both histone deacetylases. Ligand-protein docking studies suggested a high potency of human histone deacetylase inhibitors against A. thaliana HDA5. These findings suggest the potential efficacy of human histone deacetylase inhibitors in modulating plant histone deacetylases, thereby enhancing growth regulation, development, and stress resistance in plants.

SpringerLink
Ligand-Induced Variability of the FtsZ Protein Interdomain Site Pocket - Cytology and Genetics

Abstract The variability of the allosteric binding site pocket located in the interdomain cleft (IDC) of FtsZ proteins was investigated. The point-cloud models of the IDC site pockets were constructed based on 11 structures for the S. aureus complexes of FtsZ protein with 2,6-diflurobenzamides—OLQ, 9PC, OM8, OMW ZI1, ZI6, ZI7, and ZI9—which is currently deposed in the RCSB Protein Data Bank. Significant variability in the volume and shape of the IDC site pocket, formed under adaptation to the ligand, was demonstrated. Four main conformational states of the site pocket, resulting from ligand-protein fitting were selected. It indicates that the docking of the ligands into the IDC site of individual 3D-models of FtsZ protein molecules is not effective. It was concluded that virtual screening efficiency can be significantly improved by the use of an ensemble of molecular targets considering the conformational variability of the IDC site pocket of bacterial FtsZ protein.

SpringerLink

#Structural and #virologic #mechanism of the emergence of #resistance to #Mpro #inhibitors in #SARS-CoV-2, PNAS: https://www.pnas.org/doi/abs/10.1073/pnas.2404175121?af=R

We generated SARS-CoV-2 variants resistant to three SARS-CoV-2 main protease (Mpro) inhibitors (#nirmatrelvir, TKB245, and 5h), by propagating the ancestral SARS-CoV-2WK521WT in VeroE6TMPRSS2 cells with increasing concentrations of each inhibitor and examined their structural and virologic profiles.