PaPE-1

PaPE-1 binds to purified full-length human ERα and ERβ, with calculated K_i values of 10 μM and 25 μM, respectively^[1].
PaPE-1 (10 μM) restores Esr1 expression from 0.69-fold to 1.00-fold and elevates Esr2 expression from 0.89-fold to 1.64-fold in Aβ-treated cortical neurons; meanwhile, it reduces the DNA methylation rates of Esr1 and Esr2 from 80% and 48% to 39% and 24%, respectively^[3].
PaPE-1 (10 μM) increases HAT activity to 136% of the control in Aβ-treated neurons, but does not reverse the Aβ-induced elevation of HDAC activity; it exhibits no significant effect on the global DNA methylation level under Aβ conditions^[3].
PaPE-1 preferentially induces the extranuclear ER-regulated gene LRRC54 in MCF-7 cells, while it exhibits almost no activating effect on the intranuclear ER target gene PgR; the induction of LRRC54 can be blocked by Fulvestrant (HY-13636) or ERα knockdown, and this effect is not affected by GPR30 knockdown^[1].
PaPE-1 (up to 1 μM; 15-45 min) activates mTORC1, mTORC2 and MAPK signaling in MCF-7 cells, increases the phosphorylation of P70S6K, 4EBP1, SGK1, MAPK, AKT and SREBP1, and enhances the ERα-RAPTOR interaction; meanwhile, it does not significantly induce Ser118 phosphorylation associated with the pro-proliferative effect of ERα^[1].
PaPE-1 (1 μM; 4 or 24 h) regulates approximately 500 and 2200 genes, respectively, in MCF-7 cells; the mTOR inhibitor PP242 blocks approximately 60% of PaPE-1-regulated genes, and the MAPK inhibitor AZD6244 blocks nearly 50% of these genes; ChIP-seq does not detect PaPE-1-induced recruitment of ERα to chromatin^[1].
PaPE-1 (1 μM) inhibits 100 nM OA- and other FFA-induced cell proliferation in MCF-7 cells, and suppresses the proliferation of MCF-7 cells driven by 33% plasma from obese donors^[2].
PaPE-1 (1 μM; 24 h) reverses a large number of OA (100 nM)-induced gene expression changes in MCF-7 cells, including transcriptional programs associated with metabolism and cell proliferation^[2].
PaPE-1 (1 μM) inhibits OA (100 nM)-induced recruitment of ERα to chromatin and reduces the recruitment of ERα at the regulatory regions of PgR, CISH, and SREBP1^[2].
PaPE-1 (1 μM; 24 h) inhibits OA-induced metabolic reprogramming in MCF-7 cells, reduces the elevated basal respiration, maximal respiration and ATP production caused by OA, and alters the glycolysis/oxidative metabolic phenotype induced by OA^[2].
PaPE-1 (5 or 10 μM) restores the mitochondrial membrane potential after hypoxia to 94-96% of the control, and restores the membrane potential after ischemia to approximately 75%; meanwhile, it restores cellular metabolic activity after hypoxia to 96-98%, and restores metabolic activity after ischemia to 87-92%^[6].
PaPE-1 (10 μM; administered for 6 h after 24 h of Aβ_1-42 exposure) restores the Aβ-induced autophagosome level from 76% of the control to 96% in primary mouse cortical neurons, reverses Aβ-caused autophagy defects, and upregulates autophagy-related factors including Atg7, MAP1LC3AB, Becn1, Atg5, and Ambra1^[3].
PaPE-1 (10 μM) restores the level of Aβ-induced CYTO-ID-positive autophagic vesicles from 24% in the control group to 67%, and partially reverses the Aβ-triggered reduction of pre-autophagosomes, autophagosomes, and autolysosomes^[3].
PaPE-1 (10 μM; Aβ_1-42 model) partially restores the neuronal marker MAP2 and reduces Aβ-induced caspase-3 activity; the ESR1 antagonist MPP attenuates this protective effect, whereas antagonists of ESR2 or GPER1 do not exhibit the same influence, suggesting that this anti-apoptotic effect is primarily ESR1-dependent^[3].
PaPE-1 (1-10 μM) reduces hypoxia/ischemia-induced LDH release in primary neocortical neurons; at concentrations of 5 and 10 μM, it decreases caspase-3 activity to 88-96% of the control level and regulates apoptosis-related proteins including FAS, FASL, BAX, BCL2, and GSK3β ^[6].
PaPE-1 (10 μM) reduces Aβ-induced apoptotic chromatin condensation in neurons^[3].
PaPE-1 (1 μM) reduces intracellular lipid accumulation in HepG2-ERα cells under lipid-rich conditions and downregulates the expression of FASN and SREBP-1c^[4].
PaPE-1 (1 μM; 24 h) modulates the activities of PPAR, LXRα, RXR and EGR1 transcription factors induced by OA (100 nM), and antagonizes OA-driven transcriptional reprogramming related to lipid metabolism^[2].
PaPE-1 (1 μM; 24 h) reduces proton leakage and enhances mitochondrial respiratory coupling efficiency in HepG2-ERα cells^[4].
PaPE-1 (5 or 10 μM; added during the reoxygenation phase after 6 h of hypoxia/ischemia) reduces hypoxia-induced ROS levels from 212% in the control group to 145-167%, and decreases ischemia-induced ROS levels from 225% to 137-162%^[6].
PaPE-1 (1 μM; 7 min) rapidly reduces the activity of K_ATP channels in WT β cells, but this effect is absent in ERβ knockout (BERKO) β cells; 1 nM PaPE-1 does not alter K_ATP activity, supporting that this rapid effect is dependent on extra-nuclear signaling of ERβ^[7].
PaPE-1 (1, 100, 1000 nM; 48 h) reduces the expression of ion channel subunit genes including Cacna1e, Kcnma1, Kcnip1, and Scn9a in mouse pancreatic islets at the concentration of 1 μM^[7].
PaPE-1 activates eNOS/NOS activity in bovine aortic endothelial cells, with a magnitude of effect comparable to that of E2, and this effect is completely inhibited by the ER antagonist ICI 182,780^[1].
PaPE-1 (1 μM; 24 h) reverses OA-induced metabolite reprogramming in MCF-7 cells, including alterations in metabolites associated with glycolysis, fatty acid biosynthesis, and the tricarboxylic acid cycle^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.