A 10-fold more potent lysosomal autophagy inhibitor than hydroxychloroquine (HCQ)..

A novel potent ULK1 inhibitor with IC50 of 11 nM..

A small molecule autophagy enhancer that specificly inhibits myotubularin-related phosphatase MTMR14.

An orally available thioxanthone-based DNA intercalator and inhibitor of the DNA repair enzyme apurinic-apyrimidinic endonuclease 1 (APE1) potential antineoplastic activity, also inhibits autophagy.

ARN-3236 is potent, orally active and selective SIK2 inhibitor. ARN-3236 inhibited the growth of 10 ovarian cancer cell lines at an IC50 of 0.8 to 2.6 μmol/L.

Auten-99 is a novel inhibitor of the myotubularin phosphatase Jumpy (also called MTMR14), acrossing the blood-brain barrier and exerting potent neuroprotective effects.

Cambendazol is an antihelmintic that, at a dose of 50 mg/kg/day in mice, eradicates S. ratti adult worms from intestine and S. stercoralis larva from muscle.

CZC-25146 is a potent, selective and metabolically stable LRRK2 inhibitor with IC50 of 4.76 nM/6.87 nM for wild type LRRK2 and G2019S LRRK2 respectively.

CZC-54252 is a potent inhibitor of leucine-rich repeat kinase 2 (LRRK2) (IC50 values are 1.28 nM and 1.85 nM for wild-type and G2019S mutant forms of LRRK2 respectively).

DMXAA (Vadimezan) is a vascular disrupting agents (VDA) and competitive inhibitor of DT-diaphorase with Ki of 20 μM and IC50 of 62.5 μM, respectively. Phase 3.

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

GNE0877 is a highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitor with an IC50 of 3 nM.

GNE-7915 is a highly potent, selective, and brain-penetrable LRRK2 small molecule inhibitor with IC50 of 9 nM in cellular LRRK2 assay; > 100 fold selectivity against a panel of 187 kianses(Ki).

GNE-9605 is a highly potent and selective Leucine-rich repeat kinase 2 (LRRK2) inhibitor

GSK2578215A is a potent and highly selective LRRK2 inhibitor; exhibits IC50s of around 10 nM against both wild-type LRRK2 and the G2019S mutant.

GSK4112 is a Rev-erbα agonist with EC50 of 0.4 μM, also is a small molecule chemical probe for the cell biology of the nuclear heme receptor Rev-erbα.

IITZ-01 is a novel potent lysosomotropic autophagy inhibitor, has single-agent antitumor efficacy in triple-negative breast cancer in vitro and in vivo.

JH-II-127 is a highly potent, selective, and brain penetrant LRRK2 inhibitor.

LRRK2 inhibitor 18(Compound 18) is a potent azaindazole leucine-rich repeat kinase 2 (LRRK2) inhibitor with Ki of 4.1 nM.

LRRK2-IN-1 inhibits both wild-type and G2019S mutant LRRK2 kinase activity with IC50 values of 13 nM and 6 nM , respectively with 0.1 mM ATP in the assay.

Lupus erythematosus suppressant as well as an antimalerial and antirheumatic.

LV-320 (LV320) is a novel potent, cell-active, allosteric inhibitor of the autophagy-related cysteine protease ATG4B with IC50 of 24.5 uM in ATG4B cleavage assays.

LYN-1604 is a potential ULK1 agonist with IC50 of 1.66 μM against MDA-MB-231 cells and it binds to wild-type ULK1 with a binding affinity in the nanomole range (Kd=291.4 nM).

Lys01 trihydrochloride (Lys05) is a novel lysosomal autophagy inhibitor with IC50 values of 3.6, 3.8, 6 and 7.9 μM for 1205Lu, c8161, LN229 and HT-29 cell line in the MTT assay.

Lys05 is a new lysosomal autophagy inhibitor which potently accumulates within and deacidifies the lysosome of both cells and tumors, resulting in sustained inhibition of autophagy and tumor growth.

MLi-2 is an a potent, highly selective, orally available, brain penetrant inhibitor of LRRK2 with an IC50 of 0.76 nM.

MRT67307 is a potent and dual IKKϵ and TBK1 inhibitor with IC50 of 160 and 19 nM, respectively.

PF-06447475 is a highly potent, selective, brain penetrant LRRK2 inhibitor with IC0 of 3 nM/11 nM for Wt LRRK2/G2019S LRRK2 respectively.

PF-06454589 is a potent and selective LRRK2 inhibitor.

PHY34 is a potent autophagy inhibitor with cytotoxic effects by inhibiting autophagy at a late stage (MDA-MB-435 IC50=23 nM, MDA-MB-231 IC50=5.2 nM).

ROC-325 is a Novel Small Molecule Inhibitor of Autophagy with Promising Anti-Leukemic Activity.

S130 (ATG4B inhibitor S130) is a potent, specific ATG4B inhibitor with IC50 of 3.24 uM, shows strong affinity (Kd=4 uM) and specifically suppresses the activity of ATG4B, but not other proteases.

SBI-0206965 is a potent, selective and cell permeable autophagy kinase ULK1 inhibitor.

SMER28 is a small-molecule enhancer (SMER) of autophagy, inducing autophagy independently of rapamycin in mammalian cells when supplied at 47 µM.

SR-20295 (SR20295) is a novel potent ULK1 inhibitor with IC50 of 45 nM..

STF-62247 is a small molecule agonist that induces autophagy and selectively causes lethality in renal cell carcinoma (RCC) cells that have lost the von Hippel-Lindau (VHL) tumor suppressor activity (IC50 = 625 nM).

Thapsigargin is an inhibitor of microsomal Ca2+-ATPase.

Urolithin A is an intestinal metabolite of ellagic acid with antioxidant and antiproliferative effects; inhibits T24 and Caco-2 cell growth with IC50 values of 43.9 and 49 μM, respectively.

WNK463 is a pan-WNK-kinase inhibitor. It potently inhibits the in vitro kinase activity of all four WNK family members (WNK1, WNK2, WNK3, and WNK4).

WNK-IN-11 is a potent, selectiive and orally active inhibitor of WNK1 kinase.

XRK3F2 is an inhibitor of p62 (Sequestosome-1)-ZZ/ domain.

YKL-06-061 is a potent and selective SIK (salt-inducible kinase) inhibitor.

HG-10-102-01 is a potent and selective inhibitor of wild-type LRRK2(IC50=23.3 nM) and the G2019S mutant(IC50=3.2 nM)

MRT68921 is the most potent inhibitor of ULK1 and ULK2, with IC50 values of 2.9 nM and 1.1 nM, respectively.

NSC 185058 is an inhibitor of ATG4B, a cysteine protease that activates LC3B during the initiation of autophagy.

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 an

EAD1 is a potent autophagy inhibitor with antiproliferative activity in lung and pancreatic cancer cells. EAD1 also induces apoptosis.

AUTAC1 is a MetAP2-targeting autophagy-mediated degrader (AUTAC). AUTACs contain a degradation tag and a warhead to provide target specificity. AUTAC1 contains an FBnG (p-Fluorobenzyl Guanine) and a Fumagillol moiety. Fumagillol binds covalently to MetAP2.

AUTAC2 is a FKBP12-targeting autophagy-mediated degrader (AUTAC). AUTAC2 contains an FBnG (p-Fluorobenzyl Guanine) and an SLF (c ligand of FKBP) moiety. SLF binds non-covalently to FKBP12.

THZ-P1-2 is a first-in-class and selective PI5P4K inhibitor, with an IC50 of 190 nM for PI5P4Kα. THZ-P1-2 covalently targets cysteines on a disordered loop in PI5P4Kα/β/γ. THZ-P1-2 causes autophagy disruption and upregulates TFEB signaling. THZ-P1-2 displays anticancer activity in leukemia cell lines.

Zingiberene (α-Zingiberene) is a monocyclic sesquiterpene which is the predominant constituent of ginger with oil content (Zingiber officinale). Neuroprotective potential. Zingiberene triggers autophagy. Anticancer activity.

(3S,5R)-Fluvastatin D6 is the deuterium labeled (3S,5R)-Fluvastatin sodium. Fluvastatin is a first fully synthetic, competitive?HMG-CoA reductase?inhibitor with an IC50?of 8 nM. Fluvastatin protects vascular smooth muscle cells against oxidative stress through the Nrf2-dependent antioxidant pathway.

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 drug, has anti-oxidant, anti-inflammatory, antinociceptive and gastroprotective properties. Trimetazidine triggers autophagy. Trimetazidine is also a 3-hydroxyacyl-CoA dehydrogenase (HADHA) inhibitor.

(±)-Taxifolin ((±)-Dihydroquercetin) is the racemate of Taxifolin. Taxifolin exhibits important anti-tyrosinase activity. Taxifolin exhibits significant inhibitory activity against collagenase with an IC50 value of 193.3 μM.

Sedanolide, a natural compound occurring in edible umbelliferous plants, possesses anti-inflammatory and antioxidant activities.

Tat-beclin 1, a peptide derived from a region of the autophagy protein (beclin 1), is a potent inducer of autophagy and interacts with negative regulator of autophagy, GAPR-1 (GLIPR2). Tat-beclin 1 decreases the accumulation of polyglutamine expansion protein aggregates and the replication of several pathogens (including HIV-1) in vitro, and reduces mortality in mice infected with chikungunya (CHIKV) or West Nile virus (WNV).

Cearoin, isolated from Dalbergia odorifera, increases autophagy and apoptosis through the production of ROS and the activation of ERK.

Corynoxine hydrochloride, a tetracyclic oxindole alkaloid, is isolated from the hooks of Uncaria macrophylla. Corynoxine hydrochloride is a natural autophagy enhancer that promotes the clearance of alpha-synuclein via Akt/mTOR pathway.

Clematichinenoside AR is a major active ingredient that could be extracted from the traditional Chinese herb Clematis chinensis and has potent pharmacological effects on various diseases, including atherosclerosis (AS).

Olaparib D4 (AZD2281 D4) is the deuterium labeled Olaparib (AZD2281). Olaparib is a potent and orally active PARP inhibitor with IC50s of 5 and 1 nM for PARP1 and PARP2, respectively. Olaparib is an autophagy and mitophagy activator.

AUTAC4 is a mitochondria-targeting autophagy-targeting chimera (AUTAC). AUTAC4 downregulates cytosolic proteins and promots targeted mitochondrial turnover via mitophagy.

CZC-54252 hydrochloride is a potent and selective LRRK2 inhibitor with IC50s of 1.28 nM and 1.85 nM for wild-type and G2019S LRRK2, respectively. G2019S LRRK2-induced human neuronal injury is attenuated by CZC-54252 hydrochloride with an EC50 of ~1 nM.CZC-54252 hydrochloride has a neuroprotective activity.

Norswertianin, a xanthone compound, serves as a powerful anti-glioma compound. Norswertianin induces GBM cells differentiation through oxidative stress and Akt/mTOR dependent autophagy.

MRIA9 is an ATP-competitive, pan Salt-Inducible kinase (SIK) and PAK2/3 inhibitor, with IC50 values of 516 nM, 180 nM and 127 nM for SIK1, SIK2 and SIK3, respectively.

cGMP-HTL contains a HT-ligand, a linker and the Cys-S-cGMP (autophagy tag). cGMP-HTL increases the K63-linked ubiquitination of mitochondria. AUTAC (autophagy-targeting chimera) is a novel targeted-clearance strategy that contains a degradation tag (guanine derivatives) and a warhead to provide target specificity.

Tat-beclin 1 TFA, a peptide derived from a region of the autophagy protein (beclin 1), is a potent inducer of autophagy and interacts with negative regulator of autophagy, GAPR-1 (GLIPR2). Tat-beclin 1 TFA decreases the accumulation of polyglutamine expansion protein aggregates and the replication of several pathogens (including HIV-1) in vitro, and reduces mortality in mice infected with chikungunya (CHIKV) or West Nile virus (WNV).

WH-4-025 is a Salt-inducible kinase (SIK) inhibitor (WO2016023014 A2).

Autophagy-IN-C1 not only induces apoptosis but also blocks autophagy in hepatocellular carcinoma (HCC) cells.

ATG7-IN-1 is a potent and selective inhibitor of ATG7 (IC50 = 62 nM).

N6-Isopentenyladenosine (Riboprine), an RNA modification found in cytokinins, which regulate plant growth/differentiation, and a subset of tRNAs, where it improves the efficiency and accuracy of translation. N6-Isopentenyladenosine, an end product of the mevalonate pathway, is an autophagy inhibitor with an interesting anti-melanoma activity.

EB-42486 is a novel, potent, and highly selective G2019S-LRRK2 inhibitor (IC50 < 0.2 nM).

DC-LC3in-D5 acts as an autophagy inhibitor by attenuating LC3B lipidation. DC-LC3in-D5 binds with LC3B. DC-LC3in-D5 disrupts the LC3B-LBP2 interaction with an IC50 of 200 nM. DC-LC3in-D5 may contribute to anti-HCV or combination treatments in cancer through inhibiting autophagy.

Mono-Pt is the first platinum(II) complex that inhibits cancer cells through a non-DNA-binding mitophagy pathway. Mono-Pt promotes the occurrence of mitophagy in cancer cells via stimulating endoplasmic reticulum stress (ERS) and activating unfolded protein response (UPR).

SH379 is the derivative of 2-methylpyrimidine-fused tricyclic diterpene. SH379 is a potent and orally active anti-late-onset hypogonadism agent. SH379 significantly promotes the expression of the key testosterone synthesis-related enzymes StAR and 3β-HSD. SH379 stimulates autophagy through regulating AMPK/mTOR signaling pathway.

SH498, a novel Bmi-1-mediated antitumor agent, shows potent antiproliferative activity.

QW24 exerts potent anti-tumor activity by down-regulating BMI-1 and is used as an effective therapeutic agent for clinical colorectal cancer treatment.

Niacin-13C6 (Nicotinic acid-13C6) is the 13C-labeled Niacin. Niacin (Nicotinic acid) is a vitamin and is part of the vitamin B group.

Taurine-13C2,15N (2-Aminoethanesulfonic acid-13C2,15N) is the 13C- and 15N- labeled Taurine. 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.

Taurine-13C2 (2-Aminoethanesulfonic acid-13C2) is the 13C-labeled Taurine. 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.

LRRK2-IN-3 (compoubd 24) is a potent, selective, orally active and brain-penetrant inhibitor LRRK2, with IC50 of 2.6 nM in human PBMCs. LRRK2-IN-3 can be used for the research of Parkinson's disease.

LRRK2-IN-2 (compoubd 22) is a potent, selective, orally active and brain-penetrant inhibitor LRRK2, with IC50 of <0.6 nM. LRRK2-IN-2 can be used for the research of Parkinson's disease.

Atg4B inhibitor 21f is a potent competitive inhibitor for Atg4B with Ki of 3.1 uM.Atg4B inhibitor 21f enhanced the anticancer activity of anti-CRPC drugs via autophagy inhibition.

DCC-3116 (DCC3116) is a first-in-class, selective inhibitor of ULK1/2 kinases (IC50=4.7/35 nM) and autophagy.DCC-3116 is an oral ULK1/2 inhibitor targeting the autophagy pathway, a key mechanism of tumor survival and resistance to targeted therapy.

G2019S-LRRK2 inhibitor 38 is a potent, selective, brain penetrant G2019S-LRRK2 kinase inhibitor with IC50 of <1 nM, cellular EC50 of 40 nM, >2,000-fold selectivity over WT LRRK2 (cellular EC50>100 uM).G2019S-LRRK2 inhibitor 38 selectively inhibit phosphorylation of Ser935 in vitro, and in brain, lung, kidney and spleen in G2019S-LRRK2 mice.

UAMC-2526 (UAMC2526) is a low micromolar ATG4B and autophagy inhibitor.UAMC-2526 (50-100 uM) completely inhibits proliferation of HT-29 colorectal carcinoma cells.UMAC-2526 inhibits autophagy in a colorectal cancer xenograft model and potentiates chemotherapy efficacy.UMAC-256 inhibits autophagy in a healthy mouse model, animals treated withcompound UAMC-2526 showed lower levels of uncleaved (free) GFP, decreased LC3-II/LC3-I ratios and a marked increase of SQSTM1.UAMC-2526 combined with gemcitabine significantly reduced tumor growth as compared to the individual treatments, did not inhibit autophagy in the Panc02 mouse model.

PF-06447475 is a highly potent, selective, brain penetrant LRRK2 kinase inhibitor with IC50 values of 3 nM and 11 nM for WT LRRK and G2019S LRRK2, respectively. PF-06447475 can be used for parkinson's disease (PD) research.

ARN5187 trihydrochloride is a lysosomotropic REV-ERBβ ligand with a dual inhibitory activity toward REV-ERB-mediated transcriptional regulation and autophagy. ARN5187 trihydrochloride shows lysosomotropic potency and cytotoxicity. ARN5187 trihydrochloride induces apoptosis.

XL01126 is a potent degrader of LRRK2 with DC50s of 14 nM (G2019S LRRK2) and 32 nM (WT LRRK2), respectively. XL01126 can cross blood-brain barrier and be used as a degrader probe in Parkinson’s disease research. XL01126 exerts function of study of non-catalytic and scaffolding functions of LRRK2.

Forigerimod (IPP-201101) is a CD4 T-cell modulator. Forigerimod is a 21-amino-acid fragment of U1 small nuclear ribonucleoprotein 70 kDa that is phosphorylated at Ser140. Forigerimod can potently inhibit autophagy. Forigerimod can be used for the research of autoimmune disorders, such as systemic lupus erythematosus (SLE) .

MPM-1, a marine Eusynstyelamides mimic, is a potent anticancer agent. MPM-1 can rapidly kill cancer cells in vitro by inducing a necrosis-like death. MPM-1 has the ability to induce immunogenic cell death. MPM-1 causes perturbation of autophagy and lysosomal swelling in cancer cells.

Forigerimod TFA (IPP-201101 TFA) is a CD4 T-cell modulator. Forigerimod TFA is a 21-amino-acid fragment of U1 small nuclear ribonucleoprotein 70 kDa that is phosphorylated at Ser140. Forigerimod TFA can potently inhibit Autophagy. Forigerimod can be used for the research of autoimmune disorders, such as systemic lupus erythematosus (SLE) .

PF-06455943 is a leucine rich repeat kinase 2 (LRRK2) inhibitor with IC50 value of 3 nM. PF-06455943 also is a PET radioligand. PF-06455943 can be used for the research of ADME/neuro PK characterization and Parkinson disease (PD).

GLPG3970 (compound 88) is a first-in-class SIK2/SIK3 inhibitor. GLPG3970 can be used for the research of inflammation and autoimmune disease.

CUR5g is a potent autophagy inhibitor. CUR5g selectively inhibits autophagosome degradation in cancer cells by blocking autophagosome-lysosome fusion. CUR5g blocks the recruitment of STX17 to autophagosomes via a UVRAG-dependent mechanism, resulting in the inability of autophagosomes to fuse with lysosomes. CUR5g improves the anticancer effect of Cisplatin against A549 cells both in vitro and in vivo.

MTK458 (MTK-458) is a potent, selective and brain penetrant PINK1 activator, MTK-458 promotes the first step in mitophagy. MTK458 selectively activates PINK1 by stimulating dimerization and stabilization of the PINK1/TOM complex. MTK458 binds to PINK1 and stabilizes an active heterocomplex, thereby increasing mitophagy. MTK458 reduces the PINK1 substrate pS65-Ubiquitin (pUb) in primary neurons and in vivo. MTK458 drives clearance of pathologic α-synuclein in vitro and in vivo, decreases pS129 α-synuclein aggregates and normalized both brain and corresponding plasma pUb levels in both cellular and animal models of α-synuclein aggregation (PD-like pathology).

JS-017 (JS017) is a small molecule degrader of N-retinylidene-N-retinylethanolamine (A2E), one of the components of lipofuscin, degrades A2E-BDP from ARPE-19 cells with IC50 of 3.239 uM.

RH1115 is a small molecule activator and inducer of autophagy targeting Lamin A/C and LAMP1, induces changes to LAMP1 vesicle properties and alters lysosome positioning.

YTK-2205 (YTK2205) is a small molecule p62 agonist targeting ZZ domain, induces selective autophagy activation, YTK-2205 augments the translocation of p62 to mitochondria, targeting their lysosomal degradation.

DC-ATG4in is a small molecule autophagy related 4B (ATG4B) inhibitor, directly binds to ATG4B and inhibits its enzyme activity with IC50 of 3.08 uM, DC-ATG4in is an autophagy inhibitor.

EB-42168 is a potent, selective G2019S-LRRK2 kinase inhibitor with IC50 of 1.1 nM (pS935-LRRK2) in FRET-based assay, >100-fold selective over WT-LRRR2.

FX2149 (FX 2149) is a potent, BBB permeable inhibitor of LRRK2 GTP binding activity with IC90 of 10 nM, reduces PD-linked mutant LRRK2 variants (G2019S and R1441C) that bound with GTP.

MK-1468 is a potent, selective, brain-penetrant LRRK2 inhibitor with IC50 of 0.4 nM (G2019S LRRK2), potently inhibits the phosphorylation of LRRK2 serine 935 (pSer935) in hPBMCs with IC50 of 2.8 nM.

GLPG3312 is a potent and selective pan-SIK inhibitor with IC50 of 2.0/0.7/0.6 nM for SIK1/SIK2/SIK3, respectively.

JRD-SIK1/2i-4 is a potent, highly selective SIK1/2 inhibitor, modulates innate immune activation and suppress intestinal inflammation.

SK-124 (SK124) is a potent, selective, orally active SIK2/SIK3 inhibitor with IC50 of 8.8/11.3 nM in cell-based NanoBRET assays, 15-fold selectivity versus SIK1.

MR-2088 is a potent and selective ULK1/2 inhibitor with IC50 of 2.0 nM and MST Kd value of 1.5-4.4 nM (ULK1), efficiently inhibits autophagy.

SW118150 is a selective small molecule inhibitor of WNK3 kinase with IC50 of 3.0 uM, 5-fold selectivity over WNK1.

SW120619 is a specific small molecule inhibitor of WNK3 kinase with IC50 of 0.7 uM, weakly inhibits WNK1 and WNK2 with IC50 of 2.3 and 16.8 uM, respectively.

XST-14 is a potent, competitive, and highly selective inhibitor of ULK1 and exhibits an IC50 of 26.6 nM in an in vitro ULK1 kinase activity assay, respectively. XST-14 reduces the phosphorylation of the ULK1 downstream substrate and induces autophagy inhibition. It exhibits antitumor effects.