SEARCH · Engineering Papers
Results for “DRUGS”
Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Beyond darunavir: recent development of next generation HIV-1 protease inhibitors to combat drug resistance
We describe design and syntheses of a new generation of exceptionally highly potent non-peptidic HIV-1 protease inhibitors.
A membrane penetrating cyclic lipopeptide based nanocarrier for cancer drug delivery
The CLP5 self-assembles into spherical aggregates and encapsulates doxorubicin to form the CLP5@DOX nanomedicine, which exerts a combined antitumor effect by targeting caspase-3 and penetrating the cell membrane.
The structural basis for cancer drug interactions with the catalytic and allosteric sites of SAMHD1
Explore the source record for details and available documents.
Targeted inhibition of gut bacterial β-glucuronidase activity enhances anticancer drug efficacy
Irinotecan treats a range of solid tumors, but its effectiveness is severely limited by gastrointestinal (GI) tract toxicity caused by gut bacterial β-glucuronidase (GUS) enzymes. Targeted bacterial GUS inhibitors have been shown to partially alleviate irinotecan-induced GI tract damage and resultant diarrhea in mice. Here, we unravel the mechanistic basis for GI protection by gut microbial GUS inhibitors using in vivo models. We use in vitro, in fimo, and in vivo models to determine whether GUS inhibition alters the anticancer efficacy of irinotecan. We demonstrate that a single dose of irinotecan increases GI bacterial GUS activity in 1 d and reduces intestinal epithelial cell proliferation in 5 d, both blocked by a single dose of a GUS inhibitor. In a tumor xenograft model, GUS inhibition prevents intestinal toxicity and maintains the antitumor efficacy of irinotecan. Remarkably, GUS inhibitor also effectively blocks the striking irinotecan-induced bloom of Enterobacteriaceae in immune-deficient mice. In a genetically engineered mouse model of cancer, GUS inhibition alleviates gut damage, improves survival, and does not alter gut microbial composition; however, by allowing dose intensification, it dramatically improves irinotecan’s effectiveness, reducing tumors to a fraction of that achieved by irinotecan alone, while simultaneously promoting epithelial regeneration. These results indicate that targeted gut microbial enzyme inhibitors can improve cancer chemotherapeutic outcomes by protecting the gut epithelium from microbial dysbiosis and proliferative crypt damage.
Dietary modulation of gut microbiota affects susceptibility to drug-induced liver injury
Not Available
HEXIM1 controls P-TEFb processing and regulates drug sensitivity in triple-negative breast cancer
The positive transcription elongation factor b (P-TEFb), composed of CDK9 and cyclin T, stimulates transcriptional elongation by RNA polymerase (Pol) II and regulates cell growth and differentiation. Recently, we demonstrated that P-TEFb also controls the expression of EMT regulators to promote breast cancer progression. In the nucleus, more than half of P-TEFb are sequestered in the inactive-state 7SK snRNP complex. Here, we show that the assembly of the 7SK snRNP is preceded by an intermediate complex between HEXIM1 and P-TEFb that allows transfer of the kinase active P-TEFb from Hsp90 to 7SK snRNP for its suppression. Down-regulation of HEXIM1 locks P-TEFb in the Hsp90 complex, keeping it in the active state to enhance breast cancer progression, but also rendering the cells highly sensitive to Hsp90 inhibition. Because HEXIM1 is often down-regulated in human triple-negative breast cancer (TNBC), these cells are particularly sensitive to Hsp90 inhibition. Our study provides a mechanistic explanation for the increased sensitivity of TNBC to Hsp90 inhibition.
Machine Learning for Pharmacogenomics and Personalized Medicine: A Ranking Model for Drug Sensitivity Prediction
Not provided.
Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of
Explore the source record for details and available documents.
Structure of the dopamine D2 receptor in complex with the antipsychotic drug spiperone
Please check the README file for more information about the dataset.
Crystal structure of CmABCB1 multi-drug exporter in lipidic mesophase revealed by LCP-SFX
Please check the README file for more information about the dataset.
Crystal structure of CmABCB1 multi-drug exporter in lipidic mesophase revealed by LCP-SFX
Please check the README file for more information about the dataset.