Autophagy-IN-2

Autophagy-IN-2 (Compound 7h) is an autophagic flux inhibitor that induces cancer cell apoptosis, making it a valuable agent for triple-negative breast cancer research [1].

Chloroquine is a Toll-like receptor inhibitor that inhibits autophagy. Chloroquine has anti-malarial and anti-inflammatory activity and is widely used in the treatment of malaria and rheumatoid arthritis. Chloroquine also has anti-SARS-CoV-2 (COVID-19) activity and anti-HIV-1 activity.

Inflachromene (ICM) is an inhibitor of HMGB1 and HMGB expression with anti-inflammatory activity.Inflachromene reduces seizure severity in a mouse model of epilepsy by inhibiting HMGB1 translocation, inhibits endothelial proliferation through the HMGB1/2-regulated TLR4-NF-κB pathway, and inhibits autophagy by regulating Beclin 1 activity. Inflachromene can be used to study epilepsy.

Ezurpimtrostat (compound 2-2) is employed in research on fibrosis, cancer, autophagy, and diseases associated with cathepsins B (CTSB), L (CTSL), and D (CTSD).

TUN-92046 (Dimethyl 2-oxoglutarate) is a membrane-permeable alpha-ketoglutarate analogue that inhibits maladaptive autophagy in pressure overloading induced cardiomyopathy.

DCC-3116 is an orally active, selective and potent ULK1/2 inhibitor with anticancer activity.DCC-3116 inhibits autophagy and can be used in cancer research.

Atg4B-IN-2. A potent, selective Atg4B inhibitor with anticancer activity, inhibits both Atg4B and PLA2, enabling autophagy that counteracts the anticancer activity of anti-desiccation-resistant prostate cancer drugs.

DAPK-IN-2 (WAY-380496) is a DAPK inhibitor. DAPK-IN-2 has potential anticancer activity, regulates autophagy and can be used to study cerebral infarction and ischemic diseases.

AC-73 is an orally available Cluster of Differentiation 147 (CD147) inhibitor with high bioavailability that selectively disrupts the dimerization of CD147 (the binding site is in the N-terminal IgC2 domain of CD147 including Glu64 and Glu73), resulting in inhibition of the CD147 ERK1 2 STAT3 MMP-2 pathway and inhibition of liver cancer cell motility and invasion. AC-73 has antiproliferative activity and induces autophagy in leukemia cells.

FAAH-IN-2 (O-Desmorpholinopropyl Gefitinib) is a potent inhibitor of FAAH (fatty acid amide hydrolase).

Apoptosisinducer 26 (compound [AgCl(dap2SH)(PPh3)2]) is a mononuclear Ag(I) ligand-based autophagy inducer that exhibits antibacterial and anticancer activities against various bacterial strains and cancer cell lines. This compound facilitates the accumulation of Ag(I) ions in the periphery of bacteria, effectively inhibiting the growth of both Gram-positive (+) and Gram-negative (-) bacteria. Additionally, Apoptosisinducer 26 can intercalate between the base pairs of CT DNA, inducing apoptosis in A549 cells. It also possesses radical scavenging properties, which helps prevent oxidative stress.

Ch282-5, an orally active inhibitor targeting the Bcl-2 protein, promotes mitochondria-dependent apoptosis (Apoptosis) by disrupting mitophagy and the mTOR pathway. It demonstrates antiproliferative effects on colorectal cancer cells, effective both in vitro and in vivo, while also inhibiting metastasis. Further, Ch282-5 augments Oxaliplatin-induced autophagy (Autophagy) by downregulating Mcl-1 protein and raising platelet count, which helps mitigate the adverse effects of Navitoclax.

STAT3 HDAC-IN-2 (compound 18), a dual inhibitor of STAT3 and HDAC, promotes autophagy and apoptosis. This compound features an amphiphilic hydroxamic acid hybrid structure, derived from the natural product isopropanol lactone (IAL), and functions as a nanoscale anticancer agent. It has the ability to self-assemble into nanoparticles in aqueous environments, leading to enhanced tumor tissue accumulation, increased cellular uptake, and improved anticancer efficacy compared to its free state.

SW063058 is an autophagy inducer that specifically disrupts the interaction between Beclin 1 and Bcl-2 without affecting the interactions of Bcl-2 with pro-apoptotic members (such as Bax and BIM). By inhibiting the negative regulation of Beclin 1 (key to autophagy initiation) by Bcl-2, SW063058 enhances autophagic activity without inducing cytotoxicity, apoptosis, or other forms of cell death in vitro.

PD-L1degrader-2 (Compound B3) is an orally effective AUTAC degrader that degrades PD-L1 via the autophagy-lysosome pathway with a DC50 of 0.5 μM. It inhibits the interaction between PD-1 and PD-L1, with an IC50 of 22.8 nM. PD-L1degrader-2 upregulates the expression of Atg9b, Lamp1, and Mitf, activating the autophagy-lysosome system. It exhibits antitumor activity in the CT26 mouse model.

YT 6-2 is an autophagy-targeting ligand (ATL) aimed at p62 SQSTM1, used in the synthesis of AUTOTAC degrader ATC-324. ATC-324 induces the formation of AR p62 complexes, leading to the autophagic-lysosomal degradation of AR. It reduces nuclear AR levels, downregulates the expression of AR and AR-v7 target genes, and also degrades common AR mutants in PCa.

YT 6-2-PEG3-C2-NH2 is a conjugate of the autophagy-targeting ligand (ATL) targeting p62 SQSTM1 and an AUTOTAC linker. It is used in the synthesis of the AUTOTAC degrader ATC-324 for the androgen receptor (AR). ATC-324 induces the formation of the AR p62 complex, leading to autophagy-lysosomal degradation of AR. This action reduces nuclear AR levels and downregulates target gene expression of AR and AR-v7, effectively degrading common AR mutants found in prostate cancer (PCa).

YT 6-2 analog-1 (compound 2-3) serves as an autophagy-targeting ligand (ATL) aimed at p62 SQSTM1, useful in synthesizing the AUTOTAC degrader ATC-324 for the Androgen Receptor (AR). ATC-324 promotes the formation of AR p62 complexes, leading to the autophagic-lysosomal degradation of AR. It effectively reduces nuclear AR levels, downregulates the expression of AR and AR-v7 target genes, and can degrade common AR mutants found in prostate cancer (PCa).

ERK1 2 inhibitor 13 (Compound 21y) is an orally bioavailable ERK inhibitor that targets ERK1 and ERK2, with IC50 values of 91.71 nM and 97.87 nM, respectively. It effectively suppresses the proliferation of cancer cell lines MCF-7, 4T1, MDA-MB-468, and HCC1970 with IC50 values of 0.67 μM, 2.76 μM, 2.15 μM, and 1.68 μM, respectively. Additionally, it inhibits cancer cell migration, induces apoptosis and autophagy in MCF-7 cells, and demonstrates anti-tumor and anti-metastatic effects in a 4T1 xenograft mouse model.

[Ru(phen)2(HMPIP)](PF6)2 (Compound 6A) is an antitumor agent that inhibits the proliferation and migration of liver cancer cells (HepG2), while inducing apoptosis, autophagy, cell cycle arrest, and ferroptosis. It enhances antitumor activity by stimulating immune response, leading to an increase in CD8+ T cells.

SKLB-D18 is a potent and selective inhibitor of ERK1/2 and ERK5, with IC50 values of 38.69, 40.12, and 59.72 nM, respectively. It also serves as an autophagy agonist, influencing mTOR/p70S6K and NCOA4-mediated ferroptosis, potentially mitigating multidrug resistance. SKLB-D18 demonstrates significantly superior efficacy against triple-negative breast cancer (TNBC) in both in vitro and in vivo studies.

Anticanceragent 272 (Compound 2) is an anticancer agent demonstrating significant activity against bladder cancer cells (T-24) with an IC50 of 2.81 μM. It depletes glutathione (GSH) through a Fenton-like reaction, generating reactive oxygen species (ROS) and hydroxyl radicals (•OH), thereby inducing apoptosis and ferroptosis. Anticanceragent 272 enhances chemodynamic therapy (CDT) and promotes tumor cell death through mitochondrial dysfunction and autophagy. It holds potential for further research in bladder cancer.

Fluoxetine-Conjugated Platinum(IV) prodrug-1 is an eEF2K inhibitor that can hinder the proliferation of cancer cells, induce DNA damage, and cause cell cycle arrest at the S phase, leading to apoptosis (Apoptosis). It also promotes the accumulation of reactive oxygen species (ROS) and disrupts mitochondrial function. This prodrug inhibits the migration and invasion of TNBC cells by suppressing MMP-2 activity and induces autophagy in TNBC cells through AMPK activation. In the 4T1-Luc mouse model, it exhibits antitumor activity and triggers immune suppression. Fluoxetine-Conjugated Platinum(IV) prodrug-1 is relevant for research in triple-negative breast cancer (TNBC).

CHIR-99021 HCl (Laduviglusib HCl) is a highly potent and selective inhibitor of GSK-3α/β, with IC50 values of 10 nM and 6.7 nM respectively. It demonstrates remarkable selectivity for GSK-3, with over 500-fold selectivity over CDC2, ERK2, and other protein kinases. Additionally, CHIR-99021 HCl serves as a robust activator of the Wnt/β-catenin signaling pathway. Moreover, it exhibits the ability to enhance self-renewal in both mouse and human embryonic stem cells. Furthermore, CHIR-99021 HCl induces autophagy [1] [2] [3].