estropipate / Generic mfg. - LARVOL DELTA

Pharmaco-behavioral profiling identifies suppressors of autism gene-associated phenotypes in zebrafish. (PubMed, Proc Natl Acad Sci U S A) - "We identify estropipate, an estrogen receptor agonist, and paclitaxel, a microtubule inhibitor, as the top suppressors in scn1lab and dyrk1a mutants, respectively, and levocarnitine (LEVO), a mitochondrial modulator and carnitine supplement, as a top suppressor of both mutant behavioral phenotypes. Finally, we find that LEVO rescues regional brain activity deficits and dysregulated lipid metabolic pathways in mutants, as well as signaling deficits in human pluripotent stem cell-derived glutamatergic neurons carrying mutations in SCN2A and DYRK1A, demonstrating conservation of drug rescue across systems. Therefore, our study establishes a pharmaco-behavioral resource for precision medicine-based drug discovery, illuminating targets relevant to large-effect ASD genes."

Journal • Autism Spectrum Disorder • Genetic Disorders • DYRK1A

Evaluating the estrogen degradation potential of laccase and peroxidase from Bacillus ligniniphilus L1 through integrated computational and experimental approaches. (PubMed, Int J Biol Macromol) - "Notably, L1 catalase-peroxidase demonstrated significantly higher degradation for all tested compounds compared to its commercial counterpart with efficiencies of 96.16 %, 89.09 %, 74.94 %, 64.91 %, and 62.80 % against estropipate, quinestrol, estradiol valerate, estriol and estrone, respectively, revealing its potential for commercial applications. Molecular dynamics simulations revealed the interaction and stability of enzyme-estrogen complexes, with MMGBSA binding energy calculations supporting experimental results. These findings highlight the usefulness of the computational approach in elucidating the molecular mechanisms underlying enzyme-mediated bioremediation of environmental contaminants."

Journal • CAT

The action of physiological and synthetic steroids on the calcium channel CatSper in human sperm. (PubMed, Front Cell Dev Biol) - "It is mainly activated by the steroid progesterone (P4) but is also promiscuously activated by a wide range of synthetic and physiological compounds...Pregnenolone, dydrogesterone, epiandrosterone, nandrolone, and dehydroepiandrosterone acetate (DHEA) were found to activate CatSper at physiologically relevant concentrations within the nanomolar range. Like P4, most tested steroids did not significantly affect the AR while stanozolol and estropipate slightly increased sperm penetration into viscous medium. Furthermore, using a hybrid approach integrating pharmacophore analysis and statistical modelling, we were able to screen in silico for steroids that can activate the channel and define the physicochemical and structural properties required for a steroid to exhibit agonist activity against CatSper. Overall, our results indicate that not only physiological but also synthetic steroids can modulate the activity of CatSper with varying potency and if bound to CatSper prior..."

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Evaluation of the selectivity of several OATP1B biomarkers using relative activity factor method. (PubMed, Drug Metab Dispos) - "OATP1B1-specific pitavastatin uptake in hepatocytes was measured in the absence and presence of 1 µM estropipate, while NTCP-specific TCA uptake was measured in the presence of 10 µM rifampin. Our studies suggest that RAF method is a useful tool to determine the selectivity of transporter biomarkers. This method combined with pharmacogenomic and DDI studies will facilitate mechanistic interpretation and modeling of biomarker data and the selection of appropriate biomarkers for DDI evaluation."

Biomarker • Journal • SLCO2B1

"Ogeni! Ekaroo!" (,@armbit99)

Prediction of ligands to universally conserved binding sites of the influenza a virus nuclear export protein. (PubMed, Virology) - "This work presents results which are based on computational predictions that reveal interactions between available compounds and regions of the influenza A nuclear export protein which display high conservation. Due to a low probability of highly conserved regions undergoing genomic changes, these compounds may serve as ideal leads for new antivirals."

Journal • Infectious Disease

Dissecting the Contribution of OATP1B1 to Hepatic Uptake of Statins Using the OATP1B1 Selective Inhibitor Estropipate. (PubMed, Mol Pharm) - "EPP, together with rifamycin SV, was subsequently used to determine the fractions of hepatic uptake clearance ( f) of statins, including rosuvastatin, pitavastatin, and dehydropravastatin, which are reported to be mediated by OATP1B1, OATP1B3, OATP2B1, and NTCP. Finally, the magnitudes of in vivo inhibition of rosuvastatin clearance caused by EPP and rifampin (RIF) in cynomolgus monkeys were predicted by using individual transporter IC50 and fT (AUC fold change 1.28 versus 1.21, 2.71 versus 1.75, and 3.35 versus 2.83, respectively). These results suggest that EPP is an appropriate OATP1B1-selective inhibitor to establish the relative contribution of OATP1B1 to hepatic uptake in vitro and to discern the role of OATP1B1 in hepatic disposition in vivo."

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