4-Hydroxybenzophenone

4‑Hydroxybenzophenone (4HBP) is a major metabolite of Benzophenone (HY-Y0546) and is orally active. 4-Hydroxybenzophenone triggers endoplasmic reticulum stress and activates the PERK-eIF2α-ATF4-CHOP and IRE1α-XBP1s pathways, and inhibits IκB translation. 4-Hydroxybenzophenone induces endoplasmic reticulum stress, unfolded protein response activation, protein homeostasis imbalance, protein aggregation, oxidative stress, ROS accumulation, mitochondrial membrane potential decrease, ATP depletion, and cytotoxicity. 4-Hydroxybenzophenone induces neural stem cell apoptosis (apoptosis) and affects neuronal differentiation. 4-Hydroxybenzophenone promotes malignant proliferation of hepatocellular carcinoma cells and xenograft tumor growth in nude mice. 4-Hydroxybenzophenone can be used in research related to neurodevelopmental toxicity and hepatocellular carcinoma^{[1][2][3][4][5]}. In Vitro:4-Hydroxybenzophenone (4HBP) (1 μM; 7 days) primarily affects NSC proliferation and induces ER stress and apoptosis in mouse NSCs; it triggers inflammatory responses and activates the NFκB signaling pathway in hippocampal NSCs^[1].
4-Hydroxybenzophenone (1 μM) induces morphological changes in the endoplasmic reticulum of hippocampal NSCs^[1].
4-Hydroxybenzophenone (4HBP) (5 nM; 48 h) increases cell viability in HepG2 hepatocellular carcinoma cells, but not in normal LO2 hepatocytes^[2].
4-Hydroxybenzophenone (5 nM; 1-2 weeks) promotes colony formation in HepG2 hepatocellular carcinoma cells but not in normal LO2 hepatocytes^[2].
4-Hydroxybenzophenone (5 nM; beyond 30 passages) accelerates the proliferative capacity of HepG2 hepatocellular carcinoma cells but does not affect normal LO2 hepatocytes; at P30, it upregulates BIP and selectively activates the IRE1α-XBP1s signaling axis in HepG2 cells, induces XBP1s nuclear translocation, and increases protein aggregation^[2].
4-Hydroxybenzophenone exposure (5 nM; more than 30 passages) induces PERK reporter oligomerization and aggregate formation in HepG2 cells at P30^[2].
The 4-Hydroxybenzophenone-induced increase in cell viability, enhanced proliferation, and elevated colony formation ability in HepG2 cells are reversed by XBP1 knockdown or inhibition of the IRE1α-XBP1s pathway with MKC8866 (HY-104040)^[2].

4-Hydroxybenzophenone (4OH-BP) exhibits strong binding affinity with ESR1 and ESR2 in molecular docking simulations^[3].
4-Hydroxybenzophenone (1-1000 nM; 7 days) inhibits the proliferation of primary mouse hippocampal NSCs in vitro and reduces the viability of primary mouse hippocampal NSCs in vitro^[4].
4-Hydroxybenzophenone (1 μM; 7 days) treatment significantly upregulates the expression of Cxcl1 and other genes in primary mouse NSCs, with Cxcl1 being the most significantly upregulated gene^[4].
4-Hydroxybenzophenone induces endoplasmic reticulum stress and activates the PERK signaling pathway in hippocampal neural stem cells. PERK inhibition reverses the 4-Hydroxybenzophenone-induced decrease in IκBα levels in hippocampal neural stem cells and rescues hippocampal neural stem cell apoptosis^[1].

4-Hydroxybenzophenone induces ATF4-dependent p65 transcriptional regulation; ATF4 or CHOP knockdown rescues 4-Hydroxybenzophenone-triggered hippocampal neural stem cell apoptosis; it eliminates nuclear p65 aggregation and reverses apoptosis^[1].

4-Hydroxybenzophenone (1 μM; 7 days) strongly induces Cxcl1 mRNA and protein expression in primary mouse NSCs; moreover, Cxcl1 knockdown attenuates the 4HBP-induced inhibition of proliferation and increase in apoptosis, and rescues the decrease in cell viability in primary mouse NSCs^[4].
4-Hydroxybenzophenone is a hydroxybenzophenone isomer that reduces mitochondrial membrane potential (MMP) with an IC₅₀ of 41.3 μM^[5]. In Vivo:4-Hydroxybenzophenone (4HBP) (0.1-1 mg/kg/day; p.o.; throughout the 21-day gestational period) impairs hippocampal development and leads to cognitive dysfunction in offspring mice; pharmacological inhibition of PERK with GSK2606414 (HY-18072) attenuates 4HBP-induced apoptosis of NSCs in offspring, thereby improving hippocampal development and cognitive function^[1].
4-Hydroxybenzophenone (4HBP) (5 nM; subcutaneous injection; 0-12 days) specifically promotes the malignant progression of HCC cells and enhances their tumorigenic potential in vivo^[2].