cellular autophagy

MHY1485 is an mTOR activator that is cell-permeable. MHY1485 inhibits autophagosome and lysosome fusion, leading to accumulation of LC3II proteins and increased autophagosomes, thereby inhibiting cellular autophagy.

CHIR-99021 (CT99021) is an activator of the Wnt/β-catenin signaling pathway and a GSK-3α/β inhibitor (IC50=10/6.7 nM) with selective and oral activity.CHIR-99021 induces cellular autophagy, which enhances self-renewal in mouse and human embryonic stem cells.

Torin 1 is an effective inhibitor of mTORC1/2 with (IC50: 2 nM/10 nM); has 1000-fold selectivity for mTOR than PI3K.

Nur77 modulator 1 is an effective Nur77 binder (KD = 3.58 μM) that up-regulates Nur77 expression, mediates its sub-cellular localization, induces Nur77-dependent ER stress and autophagy, and leads to cell apoptosis, demonstrating anti-hepatoma activity.

BRD5631 is an autophagy enhancer that operates through an mTOR-independent pathway. It influences several cellular disease phenotypes associated with autophagy, such as protein aggregation, cell survival, bacterial replication, and inflammatory cytokine production. BRD5631 can serve as a valuable tool for studying the role of autophagy in cellular homeostasis and disease. [1].

Gefitinib hydrochloride (ZD-1839 hydrochloride) is an orally active selective and potent tyrosine kinase (EGFR) inhibitor. Gefitinib hydrochloride exhibits antitumor activity, selectively inhibits EGF-stimulated tumor cell growth, induces cellular autophagy, improves lung dysfunction, and inhibits inflammation. Gefitinib hydrochloride has antitumor activity, selectively inhibits EGF-stimulated tumor cell growth, induces cellular autophagy, ameliorates lung dysfunction, and inhibits the progression of inflammation and fibrosis.

STAT3 HDAC-IN-2 (compound 18), a dual inhibitor of STAT3 and HDAC, promotes autophagy and apoptosis. This compound features an amphiphilic hydroxamic acid hybrid structure, derived from the natural product isopropanol lactone (IAL), and functions as a nanoscale anticancer agent. It has the ability to self-assemble into nanoparticles in aqueous environments, leading to enhanced tumor tissue accumulation, increased cellular uptake, and improved anticancer efficacy compared to its free state.

Autophagyinducer 6 (Compound 3) inhibits the production of ROS and RNS by targeting COX-1 (IC50=15.3 µM) and COX-2 (IC50=4.58 µM). It facilitates the formation of autophagosomes and induces autophagy (autopagy) as a cellular protection mechanism. Additionally, Autophagyinducer 6 triggers mild apoptosis (apoptosis) and suppresses the proliferation of cancer cell lines MC38, HCT116, and HCT29 with IC50 values of 9.5, 11.5, and 17.6 µM, respectively.

ATG16L1 stabilizer-1 (compound A3B) is an FKBP12-independent stabilizer of ATG16L1 that enhances cellular autophagy (Autophagy). Regardless of the presence of FKBP12, it has an inhibitory EC50 value of 12.1 μM for ATG16L1. When used alone, ATG16L1 stabilizer-1 can induce GFP-LC3 puncta formation, with an EC50 value of 12.0 μM.

SM875 is a degrader specifically targeting the cellular prion protein (PrP) with an IC50 of 7.87 μM. By binding to the folding intermediates of PrP, SM875 facilitates their degradation via the autophagy-lysosome pathway. It acts exclusively on nascent, immature PrP molecules and does not affect mature PrP synthesized beforehand. SM875 has the potential to inhibit prion replication, making it a promising compound for research in neurodegenerative diseases, particularly prion diseases.

Timosaponin AIII (Timosaponin A3) induces autophagy in HeLa cells followed by apoptotic cell death (IC50: 10 μM). The Timosaponin AIII cellular response is mediated via inhibition of mTORC1 and induction of ER stress (IC50: 2.5 μM, BT474 cells; 6 μM, MDAMB231). The Timosaponin AIII pro-apoptotic response is selective for tumor cells over normal cells but autophagy is induced in both.

Cysmethynil is an indole-based time-dependent inhibitor of Icmt with antitumour activity and inhibitory effects on RAS membrane-binding and EGF signalling.Cysmethynil induces cell cycle arrest in G1 phase and induces cellular autophagy, and can be used for the study of solid tumours.

YW3-56 is an inhibitor of protein arginine deiminase 2 (PAD2) and PAD4 (IC50s = 0.5-1 and 1-5 μM, respectively).1It inhibits the growth of U2OS osteosarcoma cells (IC50= ~2.5 μM) in a p53-dependent mannerviainduction of SESN2 and subsequent inhibition of mTORC1. YW3-56 (10 mg kg) reduces tumor growth in an S-180 murine sarcoma tumor model. It also inhibits tumor growth in the 1883 MDA-MB-231 breast cancer bone metastasis mouse xenograft model.2 1.Wang, Y., Li, P., Wang, S., et al.Anticancer peptidylarginine deiminase (PAD) inhibitors regulate the autophagy flux and the mammalian target of rapamycin complex 1 activityThe Journal of Biological Chemisty287(31)25941-25952(2012) 2.Wang, S., Chen, X.A., Hu, J., et al.ATF4 gene network mediates cellular response to the anticancer PAD inhibitor YW3-56 in triple-negative breast cancer cellsMol. Cancer Ther.14(4)877-888(2015)

8-Aminoadenosine (8-NH2-Ado) is an RNA-directed nucleoside analogue that effectively diminishes cellular ATP levels and impedes mRNA synthesis. It also obstructs Akt mTOR signaling, inducing autophagy and apoptosis in a p53-independent manner. Its significant antitumor activity underscores its therapeutic potential.

Antiproliferative agent-5 (compound 4o) irreversibly and significantly inhibits the proliferation of gastric cancer cells, blocks the cell cycle in the G2 M phase, induces ROS accumulation, and activates cellular autophagy. Antiproliferative agent-5 can be used in anti-cancer research.

Telaglenastat (CB 839) (IC50 of 24 nM), an effective, specific, and oral inhibitor, which is bioavailable glutaminase, for recombinant human GAC.

(+)-Desmethylxestospongin B ((+)-dmXeB) acts as a powerful antagonist to the inositol triphosphate receptor (IP3R), which promotes cellular autophagy and facilitates selective apoptosis of tumor cells.

LC3in-C42 is a covalent inhibitor of LC3A B and autophagy active within cells. Selectively inhibiting the binding of P62 to LC3A B both in vitro and at the cellular level, LC3in-C42 functions similarly to D5 and is effective at lower concentrations.

4-FPBUA, a semi-synthetic analog of lichen acid, enhances the functionality of cell-based blood-brain barriers (BBB) and increases the transport of β-amyloid (Aβ) in monolayer cells. Additionally, it acts as an inhibitor of mTOR, enhancing cellular autophagy (Autophagy) which can reverse BBB disruption in vivo, making it relevant for research in Alzheimer's disease.

CORM-A1 (Sodium boranocarbonate) is a water-soluble carbon monoxide (CO) releasing molecule that facilitates the study of CO's effects on cellular systems. As CO is produced by the degradation of heme by heme oxygenase, it serves as a crucial gaseous signaling mediator in mammalian cells. CORM-A1 not only possesses antioxidant and anti-inflammatory properties but also modulates CO release in a pH and temperature-dependent manner, promoting mild vasodilation and hypotension. Additionally, CORM-A1 has been shown to provide cellular protection in primary cultures of astrocytes under oxidative stress, enhancing autophagy due to its boron content.