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- | Preclinical, Journal: Screening (ant)agonistic activities of xenobiotics on the retinoic acid receptor alpha (RAR?) using in vitro and in silico analysis. (Pubmed Central) - Jul 13, 2024
This work highlights the promising strategy for screening endocrine-disrupting effects of emerging chemicals of concern by targeting RAR? (ant)agonism.
- | Preclinical, Journal, IO biomarker, Surgery: The activation of RAR? prevents surgery-induced cognitive impairments via the inhibition of neuroinflammation and the restoration of synaptic proteins in elderly mice. (Pubmed Central) - Mar 25, 2024
prevented surgery-induced cognitive impairments via the inhibition of neuroinflammation by the reduction of the TLR4/Myd88/NF-?B pathway and the restoration of synaptic proteins by the activation of the BDNF/ERK/CREB pathway, providing a further support that RAR? could be developed as a therapeutic target for POCD.
- | Preclinical, Journal: RAR Inhibitors Display Photo-Protective and Anti-Inflammatory Effects in A2E Stimulated RPE Cells In Vitro through Non-Specific Modulation of PPAR or RXR Transactivation. (Pubmed Central) - Mar 17, 2024
Surprisingly, however, we showed that (1) Norbixin increased the RAR transactivation and (2) AGN 193109 (a high affinity pan-RAR antagonist) and BMS 493 (a pan-RAR inverse agonist), which are photoprotective against toxic blue light exposure in the presence of A2E, also inhibited PPARs transactivation and RXR transactivation, respectively. Therefore, in our in vitro model of AMD, several commercialized RAR inhibitors appear to be non-specific, and we propose that the phototoxicity and expression of IL-6 and VEGF induced by A2E in RPE cells operates through the activation of PPAR or RXR rather than by RAR transactivation.
- Developing 2nd generation retinoic acid receptor antagonists as male contraceptives | Poster Board #1032 (In-person; Poster Board #1032; Hall C (Ernest N. Morial Convention Center)) - Mar 12, 2024 - Abstract #ACSSp2024ACS_Sp_12572;
Figure 1. Beneficial optimizations, identified from structure-based drug design, on various retinoid analogs core scaffolds, led to the discovery of novel RAR antagonists with exceptional activity and selectivity.
- | Journal: Effects of retinoic acid receptor ? modulators on developmental ethanol-induced neurodegeneration and neuroinflammation. (Pubmed Central) - May 19, 2023
Since RAR? agonists including BT75 have been shown to exert anti-inflammatory effects, BT75 may rescue GABAergic cell deficits by reducing glial activation/neuroinflammation.
- | Preclinical, Journal: Anti-inflammatory Action of BT75, a Novel RAR? Agonist, in Cultured Microglia and in an Experimental Mouse Model of Alzheimer's Disease. (Pubmed Central) - Apr 24, 2023
BT75 also reduced AD-like pathology including glial activation in the icv-STZ mice. Thus, BT75 may be a promising anti-inflammatory and neuroprotective agent worthy of further AD studies.
- Combining a novel retinoic acid receptor-? agonist with immune checkpoint blockade represses lung cancer growth in vivo (Section 24; Poster Board #8) - Mar 14, 2023 - Abstract #AACR2023AACR_3984;
Given these findings we propose exploring activity of this RAR? agonist with an optimal checkpoint inhibitor in a lung cancer clinical trial.
- | Journal: Spinal cord retinoic acid receptor signaling gates mechanical hypersensitivity in neuropathic pain. (Pubmed Central) - Oct 13, 2022
Deletion of RARα in spinal PV+ neurons or application of an RARα antagonist in the spinal cord prevented the development of SNI-induced mechanical hypersensitivity. Our results identify RARα as a crucial molecular effector for neuropathic pain and a potential target for its treatment.
- Bt75, a novel rarα agonist, inhibits neuroinflammation in experimental models of alzheimer’s disease through akt/nf-κb pathway and m1-to-m2 phenotypic polarization of microglia (SDCC Halls B-H) - Oct 10, 2022 - Abstract #Neuroscience2022NEUROSCIENCE_12356;
Thus, BT75 is a promising neuroprotective agent worthy of further development into AD treatment. Supported by NIAAA R21AA027374 and NIAAA R01AA023181.
- Developing dual-selective RARα,γ antagonists as male birth control agents | Poster Board #3060 (Hall F2 (McCormick Place Convention Center)) - Aug 9, 2022 - Abstract #ACSFall2022ACS_Fall_12973;
Few of the synthesized compounds showed potent antagonism of RARα and γ without much activity at RARβ. These compounds are being evaluated in vitro and in vivo pharmacokinetic studies.
- | Journal: Constructing an MCF-7 breast cancer cell-based transient transfection assay for screening RARα (Ant)agonistic activities of emerging phenolic compounds. (Pubmed Central) - May 31, 2022
Its application in testing several emerging phenolic compounds revealed that triclosan (TCS) and tetrabromobisphenol A (TBBPA) exerted notable RARα antagonistic activities. This newly developed bioassay based on MCF-7 is promising in identifying the agonistic or antagonistic activities of xenobiotics on RARα and has good potential for studying RARα signaling-involved toxicological effects of emerging chemicals of concern.
- | Journal: Discovery of contaminants with antagonistic activity against retinoic acid receptor in house dust. (Pubmed Central) - Jan 28, 2022
BEHPP, DEHP, and TEHP were for the first time identified to be RARα antagonists with IC values of 6556, 6600, and 2538 nM, respectively. This study improved structural annotation and filled the knowledge gap regarding widespread environmental contaminants with RAR antagonistic activity.
- Development of selective RARα antagonists as male contraceptive agents (In-Person Room (Virtual Room)) - Jan 28, 2022 - Abstract #ACSSp2022ACS_Sp_13226;
One RARα-selective antagonist showed good oral bioavailability and desired pharmacokinetic properties in mice, and upon oral administration, it showed complete inhibition of embryo formation in mating studies. Modification of active compounds is ongoing to obtain additional potent and selective inhibitors with good pharmacodynamic and pharmacokinetic properties.
- | Journal: Discovery of new chalone adamantyl arotinoids having RXRα-modulating and anticancer activities. (Pubmed Central) - Nov 4, 2021
Besides, WA15 shows the induction of proteasome-dependent RXRα degradation which might enhance the WA15-induced apoptosis. Finally, the immunoblotting indicates that WA15 can inhibit the TNFα-induced IKK activation and IκBα degradation, suggesting that the anticancer activity of WA15 might be related to the inhibition of IKK/NF-κB signal pathway.
- | Journal: Retinoic acid receptor γ activation promotes differentiation of human induced pluripotent stem cells into esophageal epithelium. (Pubmed Central) - Oct 15, 2021
Finally, the immunoblotting indicates that WA15 can inhibit the TNFα-induced IKK activation and IκBα degradation, suggesting that the anticancer activity of WA15 might be related to the inhibition of IKK/NF-κB signal pathway. We revealed that RARγ activation promotes the differentiation of hiPSCs-derived foregut into EECs.
- sirolimus / Generic mfg.
[VIRTUAL] Unraveling the mechanisms of Tubulin Polymerization Promoting Protein TPPP/P25A degradation in oligodendrocytes () - Sep 29, 2021 - Abstract #MDSCongress2021MDS_Congress_844;
To assess the role of the autophagy-lysosome pathway (ALP) in TPPP/P25A proteolysis, we used pharmacological inhibitors (general lysosomal: NH4Cl, macroautophagy: 3-MA) and enhancers [Chaperone-mediated autophagy (CMA): AR7 (Atypical retinoid 7,- RARα antagonist); macroautophagy: rapamycin] of the autophagic pathways or we performed siRNA-based gene silencing of autophagy-related genes (CMA: Lamp2a, macroautophagy: Atg5) and assessed the levels of TPPP/P25A by western immunoblotting and immunocytochemistry... The ALP mediates the clearance of TPPP/P25A in oligodendrocytes; therefore manipulation of autophagic pathways may represent a successful approach for the removal of pathologically accumulated proteins in the context of MSA.
- | Journal: The Antagonist of Retinoic Acid Receptor α, ER-50891 Antagonizes the Inhibitive Effect of All-Trans Retinoic Acid and Rescues Bone Morphogenetic Protein 2-Induced Osteoblastogenic Differentiation. (Pubmed Central) - Jan 6, 2021
Neither ATRA, nor ER-50891 or their combination significantly affected the level of BMP-induced phosphorylated Smad1/5. The antagonist of RARα, ER-50891 could significantly attenuate ATRA's inhibitive effects on BMP 2-induced osteoblastogenesis.
- Development of selective RARα antagonists as male contraceptive agents (Grand Ballroom B, Pennsylvania Convention Center) - Feb 13, 2020 - Abstract #ACSSp2020ACS_Sp_14809;
Potent and selective RARα antagonists will be further evaluated in vivo for their contraceptive properties. Modification of active compounds is ongoing to obtain additional potent and selective inhibitors with suitable pharmacodynamic and pharmacokinetic properties.