Mitophagy Inducer

USP30-IN-2, a fused pyrroline, is an USP30 inhibitor with an IC₅₀ <0.1 μM. USP30-IN-2 is expected to promote mitophagy and restore mitochondrial health. USP30-IN-2 can be used for research on Parkinson's disease.

ATB1071 is a brain-penetrant and orally active p62/SQSTM1 activator. ATB1071 binds to the p62-ZZ domain, promotes PB1-dependent p62 self-polymerization, and activates p62-mediated mitophagy. ATB1071 can be used for the research of Leigh syndrome, cerebral ischemia-reperfusion injury^[1].

Chalcomoracin is an orally active anticancer agent. Chalcomoracin exhibits anticancer, antibacterial, and α-glucosidase inhibitory activities, with an IC₅₀ of 14.23 µM against yeast α-glucosidase and an IC₅₀ of 5.5 μM against FabI of Staphylococcus aureus. Chalcomoracin reduces the phosphorylation levels of ERK, JNK, and P38; enhances the phosphorylation level of ERK1/2; regulates the MAPK, mTOR, AKT, and p53 signaling pathways; upregulates the expression of Chop, Bip, PINK1, GRP78, and GADD153; and downregulates the expression of Alix. Chalcomoracin induces apoptosis (apoptosis), endoplasmic reticulum stress (endoplasmic reticulum stress), paraptosis (paraptosis), ROS production, mitophagy (mitophagy), and autophagy (autophagy); it inhibits cancer cell viability, colony-forming ability, migration, invasion, proliferation, tumorigenesis, fatty acid synthesis, S. aureus growth, vitreous-stimulated retinal cell activity, and cell cycle progression at the G0/G1 phase. Chalcomoracin can be used in research related to hepatocellular carcinoma, non-small cell lung cancer, triple-negative breast cancer, prostate cancer, proliferative vitreoretinopathy, pancreatic cancer, diabetes, and bacterial infections.

XL01126 is a blood-brain barrier-permeable, selective LRRK2 PROTAC degrader (DC₅₀: 14 nM (G2019S LRRK2) and 32 nM (WT LRRK2)). XL01126 forms a positively cooperative ternary complex with VHL E3 ubiquitin ligase and LRRK2, mediating the polyubiquitination and proteasomal degradation of LRRK2. XL01126 induces Mitophagy. XL01126 is applicable to research related to Parkinson's disease.

MTX115325 (Example 1) is an orally active, brain-penetrating USP30 inhibitor (IC₅₀=12 nM) with neuroprotective activity. MTX115325 increases ubiquitination (EC₅₀=32 nM) of the mitochondrial outer membrane protein TOM20 (a USP30 substrate), increasing mitophagy. MTX115325 prevents dopaminergic neuron loss and preserves striatal dopamine.

Diquat dibromide hydrate is a comprehensive herbicide. Diquat dibromide hydrate increases the production of ROS and triggers mitophagy. Diquat dibromide hydrate generates free radicals such as superoxide anions through redox cycles, which induce oxidative stress. Diquat dibromide hydrate is cytotoxic, reproductive, and neurotoxic. Diquat dibromide hydrate is used in cotton, soybean, and other crops to combat noxious weeds.

Dexpramipexole ((R)-Pramipexole) dihydrochloride is an orally active, blood-brain barrier permeable mitochondrial protective agent. Dexpramipexole dihydrochloride upregulates the expression of Parkin, PINK1, GPX4 and FSP1; binds to mitochondrial F1/Fo-ATP synthase; blocks the Na_v1.8 sodium channel; and inhibits the activation of the NLRP3 inflammasome. Dexpramipexole dihydrochloride induces mitophagy, inhibits ferroptosis, pyroptosis, apoptosis, neuroinflammation and eosinophilopoiesis; maintains mitochondrial function and redox homeostasis; reduces reactive oxygen species production; and decreases myocardial infarct size. Dexpramipexole dihydrochloride is applicable to studies on eosinophilic asthma, myocardial ischemia/reperfusion injury, sepsis-associated encephalopathy, analgesia, and more.

Triphenyl phosphate is an orally active, blood-brain barrier-permeable aryl organophosphate flame retardant and endocrine disruptor. Triphenyl phosphate disrupts mitochondrial dynamic balance through oxidative stress, induces excessive mitophagy and apoptosis, and ultimately leads to myocardial fibrosis. In the brain, Triphenyl phosphate activates the NF-κB inflammatory pathway by disrupting the gut microbiota, alters tryptophan metabolism and elevates neurotoxins, thereby inducing anxiety- and depression-like behaviors. In the skeletal and reproductive systems, Triphenyl phosphate inhibits osteoblast differentiation and induces germ cell apoptosis by suppressing the MAPK/ERK pathway and activating the JNK signal, respectively. In adipose and placental tissues, Triphenyl phosphate promotes lipid accumulation by activating the PI3K/AKT-PPARγ axis, and disrupts placental metabolism via the MAOA/ROS/NF-κB cascade, impairing neurodevelopment of offspring.

GSK3-IN-3 is a mitophagy inducer, inducing Parkin-dependent mitophagy. GSK3-IN-3 is also a GSK-3 inhibitor with an IC₅₀ value of 3.01 μM. GSK3-IN-3 is non-ATP nor substrate competitive and is neuroprotective against 6-OHDA.

Platycodin D2 is an orally active triterpenoid saponin found in Platycodon grandiflorum. Platycodin D2 induces mitophagy in cancer cells through NIX, thereby activating the P21/CyclinA2 pathway and promoting cell senescence. Platycodin D2 induces mitochondrial dysfunction, enhances autophagy, inhibits hepatocellular carcinoma cell proliferation, and exhibits anti-tumor activity against multiple cancer cell types. Platycodin D2 promotes mRNA expression of T-bet, GATA-3, Th1 cytokines IL-2 and IFN-γ, and Th2 cytokines IL-4 and IL-10, enhances splenocyte proliferation, and acts as a vaccine adjuvant with low rabbit red blood cell hemolytic activity. Platycodin D2 induces mitochondrial ROS production, incomplete autophagy, and ferroptosis to inhibit breast cancer cell proliferation. Platycodin D2 can be used for the research of cancer, inflammation and immunology.

T-271 is a selective inducer of mitochondrial autophagy.

PARL-IN-2 (Compound 14) is a covalent inhibitor of the mitochondrial intramembrane protease PARL with an EC₅₀ value of 0.16 μM. PARL-IN-2 leads to a robust activation of the PINK1/Parkin pathway. PARL-IN-2 promotes PINK1/Parkin-dependent mitophagy.

Dexpramipexole ((R)-Pramipexole) is an orally active, blood-brain barrier permeable mitochondrial protective agent. Dexpramipexole upregulates the expression of Parkin, PINK1, GPX4 and FSP1; binds to mitochondrial F1/Fo-ATP synthase; blocks the Na_v1.8 sodium channel; and inhibits the activation of the NLRP3 inflammasome. Dexpramipexole induces mitophagy, inhibits ferroptosis, pyroptosis, apoptosis, neuroinflammation and eosinophilopoiesis; maintains mitochondrial function and redox homeostasis; reduces reactive oxygen species production; and decreases myocardial infarct size. Dexpramipexole is applicable to studies on eosinophilic asthma, myocardial ischemia/reperfusion injury, sepsis-associated encephalopathy, analgesia, and more.

Alloc-DOX (N-Alloc doxorubicin) is a Doxorubicin (HY-15142A) prodrug. The combination of a catalyst (such as nano-palladium) and alloc-DOX leads to a decrease in cell viability and tumour growth.

MF-095 is a USP30 inhibitor. MF-095 promotes mitochondrial autophagy. MF-095 can be used in neurological disease-related research.

WJ-39 is an orally active aldose reductase (AR) inhibitor. WJ-39 improves tubular damage in diabetic nephropathy rats by activating PINK1/Parkin signaling, promoting mitophagy, and attenuating apoptosis.

Dox-btn2 is a biotin labeled Doxorubicin (HY-15142A), with a biotin label at the point of conjugation to doxorubicin at 3'-NH₂. Dox-btn2 can be used for cell imaging. While Doxorubicin is mainly accumulated in the nucleus, while Dox-btn2 is mainly located in the cytoplasm.

Acetyl zingerone is an analog of Zingerone (HY-14621). Acetyl zingerone downregulates the expression of ROS metabolism-related genes, fibroblast senescence-related genes, keratinocyte differentiation-related genes, and IL-17A target genes. Acetyl zingerone inhibits the activities of MMP-1, MMP-3, and MMP-12, as well as the activation of NLRP3 inflammasome, pyroptosis (pyroptosis), ferroptosis (ferroptosis), cartilage destruction, and UVA-induced cyclobutane pyrimidine dimer formation. Acetyl zingerone upregulates the expression of collagen, proteoglycan, extracellular matrix glycoprotein, Notch pathway, and GPX4 gene, activates Nrf2 and HO-1, induces extracellular matrix synthesis and PINK1/Parkin-mediated mitophagy (mitophagy), and promotes chondrocyte survival. Acetyl zingerone alleviates the progression of osteoarthritis in mice. Acetyl zingerone can be used in research related to skin aging, inflammatory skin diseases, osteoarthritis, melanoma, and non-melanoma skin cancer.

Doxorubicin (Hydroxydaunorubicin), a cytotoxic anthracycline antibiotic, is an anti-cancer chemotherapy agent. Doxorubicin is a potent human DNA topoisomerase I and topoisomerase II inhibitor with IC₅₀s of 0.8 μM and 2.67 μM, respectively. Doxorubicin reduces basal phosphorylation of AMPK and its downstream target acetyl-CoA carboxylase. Doxorubicin induces apoptosis and autophagy.

Triphenyl phosphate-d₁₅ is the deuterium labeled Triphenyl phosphate. Triphenyl phosphate is an orally active, blood-brain barrier-permeable aryl organophosphate flame retardant and endocrine disruptor. Triphenyl phosphate disrupts mitochondrial dynamic balance through oxidative stress, induces excessive mitophagy and apoptosis, and ultimately leads to myocardial fibrosis. In the brain, Triphenyl phosphate activates the NF-κB inflammatory pathway by disrupting the gut microbiota, alters tryptophan metabolism and elevates neurotoxins, thereby inducing anxiety- and depression-like behaviors. In the skeletal and reproductive systems, Triphenyl phosphate inhibits osteoblast differentiation and induces germ cell apoptosis by suppressing the MAPK/ERK pathway and activating the JNK signal, respectively. In adipose and placental tissues, Triphenyl phosphate promotes lipid accumulation by activating the PI3K/AKT-PPARγ axis, and disrupts placental metabolism via the MAOA/ROS/NF-κB cascade, impairing neurodevelopment of offspring.