Autophagy Inducer

Telaglenastat (CB-839) is a first-in-class, selective, reversible and orally active glutaminase 1 (GLS1) inhibitor. Telaglenastat selectively inhibits GLS1 splice variants KGA (kidney-type glutaminase) and GAC (glutaminase C) compared to GLS2. The IC₅₀s are 23 nM and 28 nM for endogenous glutaminase in mouse kidney and brain, respectively. Telaglenastat inuduces autophagy and has antitumor activity.

C646 is a selective and competitive histone acetyltransferase p300 inhibitor with K_i of 400 nM, and is less potent for other acetyltransferases.

Luteolin (Luteoline), a flavanoid compound, is a potent Nrf2 inhibitor. Luteolin has anti-inflammatory, anti-cancer properties, including the induction of apoptosis and cell cycle arrest, and the inhibition of metastasis and angiogenesis, in several cancer cell lines, including human non-small lung cancer cells.

Sodium Butyrate (sodium butanoate) is an inhibitor of HDAC, possessing anti-tumor activity.

Afatinib (BIBW 2992) is an orally active, potent and irreversible dual specificity inhibitor of ErbB family (EGFR and HER2), with IC₅₀ values of 0.5 nM, 0.4 nM, 10 nM and 14 nM for EGFR^wt, EGFR^L858R, EGFR^L858R/T790M and HER2, respectively. Afatinib can be used for the research of esophageal squamous cell carcinoma (ESCC), non-small cell lung cancer (NSCLC) and gastric cancer.

Atezolizumab (MPDL3280A) is a selective humanized monoclonal IgG1 antibody against programmed death ligand 1 (PD-L1), used for cancer research.

Colchicine, an orally active alkaloid, is a potent tubulin inhibitor and a microtubule disrupting agent. Colchicine inhibits microtubule polymerization with an IC₅₀ of 3 nM. Colchicine is also a competitive antagonist of the α3 glycine receptors (GlyRs). Colchicine prevents non-steroidal anti-inflammatory drug (NSAID)-induced small intestinal injury by inhibiting activation of the NLRP3 inflammasome. Colchicine has extensive anti-inflammatory, immunosuppressive and strong anti-fibrosis effects and has the potential for gouty arthritis research.

Mifepristone (RU486) is a progesterone receptor (PR) and glucocorticoid receptor (GR) antagonist with IC₅₀s of 0.2 nM and 2.6 nM in in vitro assay.

Taurine, a sulphur-containing amino acid and an organic osmolyte involved in cell volume regulation, provides a substrate for the formation of bile salts, and plays a role in the modulation of intracellular free calcium concentration. Taurine has the ability to activate autophagy in adipocytes.

PR-619 is a broad-range and reversible DUB inhibitor with EC₅₀s of 3.93, 4.9, 6.86, 7.2, and 8.61 μM for USP4, USP8, USP7, USP2, and USP5, respectively. PR-619 induces ER Stress and ER-Stress related apoptosis.

Imatinib (STI571) is an orally bioavailable tyrosine kinases inhibitor that selectively inhibits BCR/ABL, v-Abl, PDGFR and c-kit kinase activity. Imatinib (STI571) works by binding close to the ATP binding site, locking it in a closed or self-inhibited conformation, therefore inhibiting the enzyme activity of the protein semicompetitively. Imatinib also is an inhibitor of SARS-CoV and MERS-CoV.

Entinostat is an oral and selective class I HDAC inhibitor, with IC₅₀s of 243 nM, 453 nM, and 248 nM for HDAC1, HDAC2, and HDAC3, respectively.

Sunitinib (SU 11248) is a multi-targeted receptor tyrosine kinase inhibitor with IC₅₀s of 80 nM and 2 nM for VEGFR2 and PDGFRβ, respectively. Sunitinib, an ATP-competitive inhibitor, effectively inhibits autophosphorylation of Ire1α by inhibiting autophosphorylation and consequent RNase activation.

Adenosine (Adenine riboside), a ubiquitous and BBB-permeable endogenous autacoid, acts through the enrollment of four G protein-coupled receptors: A1, A2A, A2B, and A3. Adenosine affects almost all aspects of cellular physiology, including neuronal activity, vascular function, platelet aggregation, and blood cell regulation.

Urolithin A, a gut-microbial metabolite of ellagic acid, exerts anti-inflammatory, antiproliferative, and antioxidant properties. Urolithin A induces autophagy and apoptosis, suppresses cell cycle progression, and inhibits DNA synthesis.

Carfilzomib (PR-171) is an irreversible proteasome inhibitor with an IC₅₀ of 5 nM in ANBL-6 and RPMI 8226 cells.

Daporinad (FK866) is a non-competitive inhibitor of nicotinamide phosphoribosyltransferase (Nampt), with a K_i value of 0.3 nM. Daporinad depletes NAD+ and ATP levels, inhibits mTORC1 and MAPK/ERK pathways, and activates TFEB to induce autophagy. Daporinad causes the depletion of the endoplasmic reticulum Ca²⁺ pool, ultimately weakening the mitogen-induced Ca²⁺ signal and the activation and function of T cells. Daporinad induces cell cycle arrest and apoptosis, and inhibits cell proliferation. Daporinad can be used for the study of myeloma, liver cancer, and immunosuppression.

Metformin (1,1-Dimethylbiguanide) hydrochloride inhibits the mitochondrial respiratory chain in the liver, leading to AMPK activation and enhancing insulin sensitivity, and can be used in the study of type 2 diabetes. Metformin hydrochloride exerts central glucose-lowering effects by inhibiting Ras-related protein 1 (Rap1) in SF1 hypothalamic neurons. Metformin hydrochloride also inhibits liver oxidative stress, nitrosative stress, inflammation, and apoptosis caused by liver ischemia/reperfusion injury. In addition, Metformin hydrochloride regulates the expression of autophagy-related proteins by activating AMPK and inhibiting the mTOR signaling pathway, thereby inducing tumor cell autophagy and inhibiting the growth of renal cell carcinoma in vitro and in vivo.

Panobinostat (LBH589; NVP-LBH589) is a potent and orally active non-selective HDAC inhibitor, and has antineoplastic activities. Panobinostat induces HIV-1 virus production even at low concentration range 8-31 nM, stimulates HIV-1 expression in latently infected cells. Panobinostat induces cell apoptosis and autophagy. Panobinostat can be used for the study of refractory or relapsed multiple myeloma.

Nutlin-3a (Rebemadlin), an active enantiomer of Nutlin-3, is a potent murine double minute (MDM2) inhibitor (IC₅₀=90 nM). Nutlin-3a inhibits MDM2-p53 interactions and stabilizes the p53 protein, and induces cell autophagy and apoptosis. Nutlin-3a has the potential for the study of TP53 wild-type ovarian carcinomas.