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.

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 (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.