Autophagy Signaling

Kaempferol is found to inhibit bovine aorta myosin light chain kinase with a Ki of 0.3-0.5 microM and also is found to inhibit VEGF expression and in vitro angiogenesis through a novel ERK-NFκB-cMyc-p21 pathway.

Etoposide forms a ternary complex with DNA and the topoisomerase II enzyme (which aids in DNA unwinding), prevents re-ligation of the DNA strands, and by doing so causes DNA strands to break. Therefore, this causes errors in DNA synthesis and promotes apoptosis of the cancer cell.

CB-839 an is orally bioavailable inhibitor of glutaminase, with potential antineoplastic activity. CB-839 (Telaglenastat) also inudces autophagy and has antitumor activity.

Chloroquine phosphate is a 4-aminoquinoline anti-malarial and anti-rheumatoid agent, also acting as an ATM activator.

Spautin-1 is a novel autophagy inhibitor, IM inhibited the growth of K562 cells with IC50 of 1.03μM. In contrast, co-treatment with Spautin-1 increased IM-induced inhibition of cell viability with IC50 of 0.45 μM.

Doxorubicin is an antibiotic agent that inhibits DNA topoisomerase II and induces DNA damage and apoptosis.

Valproic acid is an HDAC inhibitor, with IC50 in the range of 0.5 and 2 mM, also inhibits HDAC1 (IC50, 400 μM), and induces proteasomal degradation of HDAC2; Valproic acid sodium salt is used in the treatment of epilepsy, bipolar disorder and prevention of migraine headaches.

Polydatin protects cerebral cells from ischemic damages via improvement of microcirculation and inhibition of platelet aggregation. In addition, polydatin inhibits ICAM-1 expression in endothelial cells stimulated by lipopolysaccharide; it also attenuates adhesion between white blood cells and endothelial cells.

Resveratrol has a wide spectrum of targets including cyclooxygenases(i.e. COX, IC50=1.1 μM), lipooxygenases???LOX, IC50=2.7 μM???, kinases, sirtuins and other proteins. It has anti-cancer, anti-inflammatory, blood-sugar-lowering and other beneficial cardiovascular effects.

Plerixafor is an immunostimulant used to multiply hematopoietic stem cells and it is a chemokine receptor-4 antagonist for mobilization of hematopoietic stem cells for transplantation.

Plerixafor is an immunostimulant used to multiply hematopoietic stem cells and it is a chemokine receptor-4 antagonist for mobilization of hematopoietic stem cells for transplantation.

U0126-EtOH is an inhibitor of both MEK1 and MEK2 with an IC50 of 72 nM and 58 nM respectively.

Metformin is an AMP-activated protein kinase (AMPK) activator that improves glycemic control by improving insulin sensitivity and decreasing intestinal absorption of glucose.

ABT-737 is a pan-Bcl-2 inhibitor. IC50 values ranged from 192 nM (the pre-B cell line Hal-01) to <10 μM (Nalm-6, K562 and HL-60).

AMD 3465 is a potent, selective CXCR4 antagonist.

PP242 is a potent and selective mTOR inhibitor in both mTORC1 and mTORC2.

Aloe emodin is a anthraquinone present in aloe latex, an exudate from the aloe plant. It has a strong stimulant-laxative action.

Sunitinib (SU 11248) is a multi-targeted receptor tyrosine kinase inhibitor with IC50s of 80 nM and 2 nM for VEGFR2 and PDGFRβ, respectively.

Metformin hydrochloride is a biguanide hypoglycemic agent used in the treatment of non-insulin-dependent diabetes mellitus not responding to dietary modification.

INCB018424 is a potent and selective inhibitor of Janus-associated kinase (JAK) 1 and 2, with IC50 to be 2.7, 4.5 and 332 nM for JAK1, JAK2 and JAK3 respectively;

3-Methyladenine is an inhibitor of class III phosphatidylinositol 3-kinase (PI 3-kinase).

MRT68921 is a potent and dual autophagy kinase ULK1/2 inhibitor with IC50 of 2.9 nM and 1.1 nM, respectively.

Crenolanib (CP-868596) is an orally bioavailable, selective small molecule inhibitor of the PDGFR tyrosine kinase, inhibiting both PDGFRA and PDGFRB at picomolar concentrations.

Reparixin is a potent inhibitor of both CXCL8 receptors CXCR1/2, it inhibits weakly CXCR2-mediated cell migration (IC50=100 nM), whereas it strongly blocks CXCR1-mediated chemotaxis (IC50=1 nM).

Vorinostat is an inhibitor of HDACs, inhibiting deacetylation and leading to an accumulation of both hyperacetylated histones and transcription factors.

Acadesine is a selective activator of AMPK in both hepatocytes and adipocytes.

Emodin is a purgative resin, from rhubarb, the buckthorn and Japanese Knotweed (Fallopia japonica). It belongs to a family of compounds called anthraquinones, which have shown anti-inflammatory and anticancer effects

SCH527123 is a potent and selective antagonist of the human CXCR1 and CXCR2 receptors with IC50 of 42 nM and 3 nM, respectively.

Sunitinib is an oral, small-molecule, multi-targeted receptor tyrosine kinase (RTK) inhibitor for the treatment of renal cell carcinoma (RCC) and imatinib-resistant gastrointestinal stromal tumor (GIST).

SBI-0206965 is a potent, selective and cell permeable autophagy kinase ULK1 inhibitor with IC50 of 108 nM for ULK1 kinase activity and 711 nM for the highly related kinase ULK2 .

Dexamethasone is a potent synthetic member of the glucocorticoid class of steroid drugs. It acts as an anti-inflammatory and immunosuppressant. Its potency is about 20-30 times that of the naturally occurring hormone hydrocortisone and 4-5 times of prednisone.

Quercetin inhibits many enzyme systems including tyrosine protein kinase, phospholipase A2, phosphodiesterases, mitochondrial ATPase, PI 3-kinase and protein kinase C.

Berberine hydrochloride was novelly found that it has various beneficial effects on the cardiovascular system and significant anti-inflammatory activities. Berberine can effectively reduce intracellular superoxide levels in LPS-stimulated macrophages. Such a restoration of cellular redox by berberine is mediated by its selective inhibition of gp91phox expression and enhancement of SOD activity.

AMD 070 is a CXCR4 chemokine receptor antagonist.

Mdivi-1 is a selective cell-permeable inhibitor of mitochondrial division DRP1 (dynamin-related GTPase) and mitochondrial division Dynamin I (Dnm1) with IC50 of 1-10 uM.

GNE-9605 is a highly potent and selective leucine-rich repeat kinase 2 (LRRK2) inhibitor with Ki and IC50 of 2 nM and 19 nM, respectively.

Pitavastatin Calcium is a competitive inhibitor of the enzyme HMGCR (HMG-CoA reductase) results in a reduction in LDL cholesterol synthesis.

Celastrol is a triterpenoid antioxidant compound isolated from the Chinese Thunder of God vine (T. wilfordii). In an isolated rat liver assay of lipid peroxidation, celastrol had an IC50 value of 7 µM, equivalent to about 15 times the antioxidant potency of α-tocopherol.

SCH 563705 is a potent dual CXCR2(IC50= 1.3 nM)/CXCR1(IC50= 7.3 nM) antagonist.

TAE684 is a inhibitor of ALK and also a potent inhibitor of LRRK2 kinase activity (IC(50) of 7.8nM against wild-type LRRK2, 6.1nM against the G2019S mutant).

Olaparib (AZD2281) is an inhibitor of poly ADP ribose polymerase (PARP), an enzyme involved in DNA repair.

PF-04691502 is a PI3K/mTOR kinase inhibitor, is also an agent targeting the phosphatidylinositol 3 kinase (PI3K) and mammalian target of rapamycin (mTOR) in the PI3K/mTOR signaling pathway.

GPR35 agonist 1 (compound 50) is a potent and specific G protein-coupled receptor-35 (GPR35)/CXCR8 agonist with an EC50 of 5.8 nM, displays good druggability.

Avermectin B1 (Abamectin) is a widely used insecticide and anthelmintic.

WZ811 is a C-X-C chemokine receptor type 4 (CXCR4) antagonist (EC50 = 0.3 nM). Inhibits CXCR4/stromal cell-derived factor-1 (SDF-1)-mediated modulation of cAMP in vitro (EC50 = 1.2 nM).

MSX-122 is an orally bioavailable inhibitor of CXCR4 (IC50 = ~10 nM) with potential antineoplastic and antiviral activities. CXCR4 inhibitor MSX-122 binds to the chemokine receptor CXCR4, preventing the binding of stromal derived factor-1 (SDF-1) to the CXCR4 receptor and receptor activation, which may result in decreased tumor cell proliferation and migration.

FMK 9a is an autophagin-1 inhibitor with IC50 values of 80 and 73 μM in FRET and LRA assay.

Sulfosuccinimidyl oleate (Sulfo-N-succinimidyl oleate) is a long chain fatty acid that inhibits fatty acid transport into cells. Sulfosuccinimidyl oleate is a potent and irreversible inhibitor of mitochondrial respiratory chain.

CXCR2-IN-1 is a central nervous system penetrant CXCR2 antagonists with a pIC50 of 9.3.

GSK2578215A is a potent leucine-rich repeat kinase 2 (LRRK2) inhibitor (IC50 values are 8.9 and 10.1 nM respectively for LRRK2[G2019S] mutant and wild-type LRRK2 respectively).