Autophagy Inducer

Sepantronium bromide (YM-155) is a survivin inhibitor with an IC₅₀ of 0.54 nM.

Carvedilol (BM 14190) is a non-selective β/α-1 blocker. Carvedilol inhibits lipid peroxidation in a dose-dependent manner with an IC₅₀ of 5 μM. Carvedilol is a multiple action antihypertensive agent with potential use in angina and congestive heart failure. Carvedilol is an autophagy inducer that inhibits the NLRP3 inflammasome.

Nordihydroguaiaretic acid is a 5-lipoxygenase (5LOX) (IC₅₀=8 μM) and tyrosine kinase inhibitor.

Lonafarnib (Sch66336) is an orally active, blood-brain barrier penetrant farnesyltransferase (FPTase) inhibitor. Lonafarnib increases the phosphorylation levels of Akt, CaMKII and CREB, upregulates BDNF expression in the hippocampus, elevates the content of α7nAChR on cell membranes, and blocks the isoprenylation of H-Ras. Lonafarnib repairs synapses and reverses spatial memory deficits in Aβ1-42 model mice. Lonafarnib inhibits RSV fusion and replication, and alleviates virus-induced lung injury. Lonafarnib activates the lysosomal and autophagic pathways, and reduces the phosphorylation and aggregation of tau. Lonafarnib acts synergistically with Sorafenib (HY-10201) to promote apoptosis, and inhibits the proliferation and invasion of melanoma cells. Lonafarnib inhibits the farnesylation of progerin, repairs nuclear membrane defects, and activates the cGAS-STING-STAT1 signaling pathway. Lonafarnib can be used in research related to diseases including Alzheimer's disease, viral infections, melanoma, and progeria.

Ginsenoside Rb1, a main constituent of the root of Panax ginseng, inhibits Na⁺, K⁺-ATPase activity with an IC₅₀ of 6.3±1.0 μM. Ginsenoside also inhibits IRAK-1 activation and phosphorylation of NF-κB p65 .

BI-D1870 is an ATP-competitive, cell permeable and brain penetrated inhibitor of RSK isoforms, with IC₅₀s of 31 nM/24 nM/18 nM/15 nM for RSK1/RSK2/RSK3/RSK4, respectively.

Spironolactone is an aldosterone antagonist that acts on the aldosterone mineralocorticoid receptor (IC₅₀=24 nM) and androgen receptor (IC₅₀=77 nM), promotes podocyte autophagy and regulates pain. Spironolactone improves hypertension-related vascular hypertrophy and remodeling by reducing angiotensin II (Ang II)-induced inflammation, reduces aldosterone-induced vascular and soft tissue calcification through PIT1-dependent signaling, and alleviates vascular dysfunction in type II diabetic mice by reducing oxidative stress and restoring NO/GC signaling; at low concentrations, it and its metabolites can interfere with aldosterone biosynthesis in the adrenal cortex and inhibit voltage-dependent Ca²⁺ channels to exert antihypertensive effects.

Isoniazid (INH) is a proagent and must be activated by a bacterial catalase-peroxidase enzyme KatG. Isoniazid is bactericidal to rapidly dividing mycobacteria and has anti-tuberculostatic activity.

Cabazitaxel is a semi-synthetic derivative of the natural taxoid 10-deacetylbaccatin III with potential antineoplastic activity.

6-Thioguanine (Thioguanine; 2-Amino-6-purinethiol) is an anti-leukemia and immunosuppressant agent, acts as an inhibitor of SARS and MERS coronavirus papain-like proteases (PLpros) and also potently inhibits USP2 activity, with IC₅₀s of 25 μM and 40 μM for Plpros and recombinant human USP2, respectively.

Polydatin (Piceid), extracted from the roots of Reynoutria japonica, a widely used traditional Chinese remedies, possesses anti-inflammatory activity in several experimental models. Polydatin (Piceid) inhibits G6PD and induces oxidative and ER stresses.

Mocetinostat (MGCD0103) is a potent, orally active and isotype-selective HDAC (Class I/IV) inhibitor with IC₅₀s of 0.15, 0.29, 1.66 and 0.59 μM for HDAC1, HDAC2, HDAC3 and HDAC11, respectively. Mocetinostat shows no inhibition on HDAC4, HDAC5, HDAC6, HDAC7, or HDAC8.

Bicalutamide is an orally active non-steroidal androgen receptor (AR) antagonist. Bicalutamide can be used for the research of prostate cancer.

Trimetazidine is a selective long chain 3-ketoyl coenzyme A thiolase inhibitor with an IC₅₀ of 75 nM, which can inhibit β-oxidation of free fatty acid (FFA). Trimetazidine is an effective antianginal agent and a cytoprotective agent, has anti-oxidant, anti-inflammatory, antinociceptive and gastroprotective properties. Trimetazidine triggers autophagy. Trimetazidine is also a 3-hydroxyacyl-CoA dehydrogenase (HADHA) inhibitor.

Rottlerin, a natural product purified from Mallotus Philippinensis, is a specific PKC inhibitor, with IC₅₀ values for PKCδ of 3-6 μM, PKCα,β,γ of 30-42 μM, PKCε,η,ζ of 80-100 μM. Rottlerin acts as a direct mitochondrial uncoupler, and stimulates autophagy by targeting a signaling cascade upstream of mTORC1. Rottlerin induces apoptosis via caspase 3 activation. Rottlerin inhibits HIV-1 integration and Rabies virus (RABV) infection.

TFEB activator 1 is an orally effective, mTOR-independent activator of TFEB. TFEB activator 1 significantly promotes the nuclear translocation of Flag-TFEB with an EC₅₀ of 2167 nM. TFEB activator 1 enhances autophagy without inhibiting the mTOR pathway and has the potential for neurodegenerative diseases treatment.

Tepotinib (EMD-1214063) is an orally active and highly selective, reversible, ATP-competitive c-Met inhibitor with an IC₅₀ of 3 nM, >200-fold selective for c-Met than IRAK4, TrkA, Axl, IRAK1, and Mer. Tepotinib inhibits c-Met phosphorylation and induces autophagy. Tepotinib has antitumor effects.

Dihydromyricetin is a potent inhibitor with an IC₅₀ of 48 μM on dihydropyrimidinase. Dihydromyricetin can activate autophagy through inhibiting mTOR signaling. Dihydromyricetin suppresses the formation of mTOR complexes (mTORC1/2). Dihydromyricetin is also a potent influenza RNA-dependent RNA polymerase inhibitor with an IC₅₀ of 22 μM.

2-Methoxyestradiol (2-ME2), an orally active endogenous metabolite of 17β-estradiol (E2), is an apoptosis inducer and an angiogenesis inhibitor with potent antineoplastic activity. 2-Methoxyestradiol also destablize microtubules. 2-Methoxyestradio, also a potent superoxide dismutase (SOD) inhibitor and a ROS-generating agent, induces autophagy in the transformed cell line HEK293 and the cancer cell lines U87 and HeLa.

Efavirenz (DMP 266) is a potent inhibitor of the wild-type HIV-1 reverse transcriptase with a K_i of 2.93 nM and exhibits an IC₉₅ of 1.5 nM for the inhibition of HIV-1 replicative spread in cell culture.