Autophagy Inducer

Ruxolitinib phosphate (INCB018424 phosphate) is a potent JAK1/2 inhibitor with IC₅₀s of 3.3 nM/2.8 nM, respectively, showing more than 130-fold selectivity over JAK3.

Temsirolimus is an inhibitor of mTOR with an IC₅₀ of 1.76 μM. Temsirolimus activates autophagy and prevents deterioration of cardiac function in animal model.

Glibenclamide (Glyburide) is an orally active ATP-sensitive K⁺ channel (K_ATP) inhibitor and can be used for the research of diabetes and obesity. Glibenclamide inhibits P-glycoprotein. Glibenclamide directly binds and blocks the SUR1 subunits of K_ATP and inhibits the cystic fibrosis transmembrane conductance regulator protein (CFTR). Glibenclamide interferes with mitochondrial bioenergetics by inducing changes on membrane ion permeability. Glibenclamide can induce autophagy.

Colistin sulfate is a polypeptide antibiotic which inhibits gram-negative bacteria by binding to lipopolysaccharides and phospholipids in the outer cell membrane of gram-negative bacteria.

Ursolic acid (Prunol) is a natural pentacyclic triterpenoid carboxylic acid, exerts anti-tumor effects and is an effective compound for cancer prevention and therapy.

Itraconazole (R51211) is a triazole antifungal agent and a potent and orally active Hedgehog (Hh) signaling pathway antagonist with an IC₅₀ of ~800 nM. Itraconazole potently inhibits lanosterol 14α-demethylase (cytochrome P450 enzyme), thereby inhibits the oxidative conversion of lanosterol to ergosterol. Itraconazole has anticancer and antiangiogenic effects. Itraconazole is a oxysterol-binding protein (OSBP) inhibitor.

Belinostat (PXD101; PX105684) is a potent HDAC inhibitor with an IC₅₀ of 27 nM in HeLa cell extracts.

Fasudil (HA-1077; AT877) Hydrochloride is a nonspecific RhoA/ROCK inhibitor and also has inhibitory effect on protein kinases, with an K_i of 0.33 μM for ROCK1, IC₅₀s of 0.158 μM and 4.58 μM, 12.30 μM, 1.650 μM for ROCK2 and PKA, PKC, PKG, respectively. Fasudil Hydrochloride is also a potent Ca²⁺ channel antagonist and vasodilator.

Chlorpromazine hydrochloride is an orally active, blood-brain barrier-transparent antipsychotic agent that effectively antagonises D2 dopamine receptors and 5-HT_2A, which is widely used in schizophrenia and other psychiatric disorders. Chlorpromazine hydrochloride exerts anti-cancer activity through a variety of pathways, including anti-proliferation, induction of autophagy and cycle arrest (G2-M phase), inhibition of cytochrome c oxidase (CcO), inhibition of tumour growth and metastasis, and inhibition of tumour immune escape. Chlorpromazine hydrochloride also blocks hNa_v1.7 channels (IC₅₀=25.9 μM; concentration-dependent) and HERG potassium channels (IC₅₀=21.6 μM), which has potential for analgesic and cardiac arrhythmic studies. Chlorpromazine hydrochloride also can inhibit clathrin-mediated endocytosis.

Pazopanib (GW786034) is a novel multi-target inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFRβ, c-Kit, FGFR1, and c-Fms with IC₅₀s of 10, 30, 47, 84, 74, 140 and 146 nM, respectively.

Sildenafil (UK-92480) is a potent phosphodiesterase type 5 (PDE5) inhibitor with an IC₅₀ of 5.22 nM.

Bexarotene (LGD1069) is a high-affinity and selective retinoid X receptors (RXR) agonist with EC₅₀s of 33, 24, 25 nM for RXRα, RXRβ, and RXRγ, respectively. Bexarotene shows limited affinity for RAR receptors (EC₅₀ >10000 nM). Bexarotene can be used for the research of cutaneous T-cell lymphoma.

SRT 1720 is a selective activator of human SIRT1 with an EC_1.5 of 0.16 μM, and shows less potent activities for SIRT2 and SIRT3 with EC_1.5s of 37 μM and > 300 μM, respectively.

Bosutinib is an orally active Src/Abl tyrosine kinase inhibitor with IC₅₀ of 1.2 nM and 1 nM, respectively.

Vinorelbine (ditartrate) is an anti-mitotic agent which inhibits the proliferation of Hela cells with IC₅₀ of 1.25 nM.

Tubastatin A is a potent and selective HDAC6 inhibitor with an IC₅₀ of 15 nM in a cell-free assay, and is selective (1000-fold more) against all other isozymes except HDAC8 (57-fold more). Tubastatin A also inhibits HDAC10 and metallo-β-lactamase domain-containing protein 2 (MBLAC2).

Veliparib (ABT-888) is a potent PARP inhibitor, inhibiting PARP1 and PARP2 with K_is of 5.2 and 2.9 nM, respectively.

Parthenolide is a sesquiterpene lactone found in the medicinal herb Feverfew. Parthenolide exhibits anti-inflammatory activity by inhibiting NF-κB activation; also inhibits HDAC1 protein without affecting other class I/II HDACs.

Salvianolic acid B is an active ingredient of Salvia miltiorrhiza, which has been widely applied in China for the management of various microcirculation-related disorders, such as cardiovascular disease, cerebrovascular disease, and diabetic vascular complication.

Ixazomib (MLN2238) is a selective, potent, and reversible proteasome inhibitor, which inhibits the chymotrypsin-like proteolytic (β5) site of the 20S proteasome with an IC₅₀ of 3.4 nM (K_i of 0.93 nM).