parkin

USP30 inhibitor 18 is a selective USP30 inhibitor with an IC50 of 0.02 μM. USP30 inhibitor 18 increases protein ubiquitination and accelerates mitophagy[1]. [1]. Arthur F Kluge, et al. Novel highly selective inhibitors of ubiquitin specific protease 30 (USP30) accelerate mitophagy. Bioorg Med Chem Lett. 2018 Aug 15;28(15):2655-2659.

Salidroside is a bioactive phenolic glycoside compound isolated from Rhodiola rosea and is a prolyl endopeptidase inhibitor. Salidroside can alleviate cachexia symptoms in a tumor cachexia mouse model by activating mTOR signaling and protect dopaminergic neurons by enhancing PINK1/Parkin-mediated mitochondrial autophagy. Salidroside can also inhibit the growth of cancer cells by regulating the CDK4-cyclin D1 pathway to block the G1 phase and/or regulating the Cdc2-cyclin B1 pathway to block the G2 phase.

P62-mediated mitophagy inducer (PMI) is a regulator of mitophagy.

BIO-2007817 is a positive allosteric modulator (PAM) of Parkin, an E3 ubiquitin ligase. This compound enhances the activity of wild-type Parkin, stimulates Parkin's autoubiquitination, and induces the appearance of mono-ubiquitinated forms of Miro1 (a Parkin substrate) with an EC50 of 0.17 μM.

PARL-IN-2 (Compound 14) is a covalent inhibitor of the mitochondrial inner membrane protease PARL, with an EC50 value of 0.16 μM. It strongly activates the PINK1/Parkin pathway and enhances PINK1/Parkin-dependent mitophagy.

THX6 is an activator of human mitochondrial protease ClpP, with an EC50 of 1.18 μM. It displays cytotoxicity in ONC201-resistant SU-DIPG-VI cells, with an IC50 of 0.13 μM. THX6 inhibits the expression of mitochondria-related proteins (such as parkin, TFAM, NRF1, SDHA), leading to impaired mitochondrial function. Additionally, THX6 affects cell membrane lipid metabolism and exhibits antitumor potential.

PARL-IN-1 TFA is a potent PARL inhibitor with an IC50 value of 28 nM. It inhibits PARL, leading to significant activation of the PINK1/Parkin pathway. Additionally, PARL-IN-1 TFA enhances PINK1/Parkin-dependent mitophagy.

Y040-7904 is a potential mitochondrial autophagy activator. It enhances mitochondrial autophagy by facilitating the transport of mitochondria to autophagosomes and promoting the fusion of autophagosomes with autolysosomes. Y040-7904 induces mitochondrial autophagy through the SIRT1/FoxO3 pathway and upregulates the levels of Parkin, PINK1, and LC3II/I. Additionally, Y040-7904 reduces Aβ accumulation in both in vitro and in vivo Alzheimer's disease models.

Antiproliferative agent-70 (compound 23) is a potent antiproliferative compound with anticancer properties. It induces the depolarization of matrix metalloproteinases (MMP), disrupts mitochondrial function, and promotes mitophagy and ferroptosis. The compound enhances the expression of proteins such as PINK1, p-Parkin, p53, and p21, and increases intracellular ROS levels.

LCL768 is a ceramide analogue that attenuates PARKIN succinylation, thereby promoting PARKIN activation and mitophagy. It induces the accumulation of CerS1-mediated endogenous C18-ceramide in mitochondria, facilitating mitophagy through DRP1 activation via C644 site nitrosylation. Additionally, LCL768 alters mitochondrial metabolism, depleting fumarate and inhibiting tumor growth. Furthermore, it ameliorates sensorimotor deficits in neurodegenerative diseases such as ALS.

T0467 is a chemical compound that activates the translocation of parkin to the mitochondria in a PINK1-dependent manner in vitro. However, T0467 does not induce the accumulation of PINK1 in the mitochondria of dopaminergic neurons. As a result, T0467 shows promise as a potential compound for activating the PINK1-Parkin signaling pathway and can be utilized in research related to Parkinson's disease and related disorders.

FT3967385 is a newly developed compound that functions as a USP30 inhibitor, emulating the genetic deficiency of USP30. This inhibition serves as a catalyst for the amplification of mitochondrial ubiquitylation through the PINK1-PARKIN pathway.

HMS607P03 is an activator of SIRT1 which induces autophagic cell death via the AMPK-mTOR-ULK complex and induces mitophagy by the SIRT1-PINK1-Parkin pathway. HMS607P03 downregulates 14-3-3γ, catalase, profilin-1, and HSP90α.

FT385 is a novel USP30 inhibitor, recapitulating genetic loss of USP30 and setting the trigger for PINK1-PARKIN amplification of mitochondrial ubiquitylation.

PARL-IN-1, a potent PARL inhibitor, exhibits an IC50 value of 28 nM. It effectively inhibits PARL, consequently robustly activating the PINK1/Parkin pathway and promoting PINK1/Parkin-dependent mitophagy.

GSK3-IN-3 is a mitochondrial autophagy (mitophagy) inducer and GSK-3 inhibitor (IC50: 3.01 μM) that induces parkin-dependent mitochondrial autophagy. GSK3-IN-3 is non-ATP and non-substrate competitive and neuroprotective against 6-OHDA.

2-APQC is a selective, orally active Sirtuin-3 (SIRT3) agonist (Kd=2.756 μM) that modulates mitochondrial homeostasis. It attenuates ISO-induced myocardial hypertrophy and fibrosis in vivo and in vitro, making it suitable for heart failure research. 2-APQC inhibits mTOR-p70S6K, JNK, TGF-β/Smad3, and ROS-p38MAPK pathways while activating PYCR1 and AMPK-Parkin, thereby suppressing necrosis and mitigating mitochondrial oxidative damage.

Penisterpenoid A (Compound 1), an activator of the PINK1/Parkin mitochondrial autophagy signaling pathway, is derived from the rhizosphere fungi of the medicinal plant Bupleurum. In both in vitro and in vivo settings, Penisterpenoid A effectively reduces lipid accumulation and significantly enhances mitochondrial function.

Afzelin (Standard) is a reference standard for research and analysis in studies involving Afzelin. Afzelin (Kaempferol-3-O-rhamnoside) has several cellular activities such as DNA-protective, antibacterial, antioxidant, and anti-inflammatory as well as UV-absorbing activity and may protect human skin from UVB-induced damage by a combination of UV-absorbing and cellular activities. Afzelin attenuates the mitochondrial damage, enhances mitochondrial biogenesis and decreases the level of mitophagy-related proteins, parkin and PTEN-induced putative kinase 1.

Salidroside (Standard) is a reference standard for research and analysis in studies involving Salidroside. Salidroside is a bioactive phenolic glycoside compound isolated from Rhodiola rosea and is a prolyl endopeptidase inhibitor. Salidroside can alleviate cachexia symptoms in a tumor cachexia mouse model by activating mTOR signaling and protect dopaminergic neurons by enhancing PINK1/Parkin-mediated mitochondrial autophagy. Salidroside can also inhibit the growth of cancer cells by regulating the CDK4-cyclin D1 pathway to block the G1 phase and/or regulating the Cdc2-cyclin B1 pathway to block the G2 phase.

Afzelin (Kaempferol-3-O-rhamnoside) exhibits several cellular activities such as DNA-protective, antibacterial, antioxidant, anti-inflammatory, and UV-absorbing properties, potentially protecting human skin from UVB-induced damage through a combination of UV-absorbing and cellular actions. Afzelin mitigates mitochondrial damage, promotes mitochondrial biogenesis, and reduces levels of mitophagy-related proteins, parkin and PTEN-induced putative kinase 1.

Valinomycin (NSC-122023) is a cyclic depsipeptide antibiotic and a potassium-specific ionophore.Valinomycin induces PINK1 activation and promotes Parkin phosphorylation at Ser65.