SIRT3 Agonist

2-APQC is an orally active and selective agonist of Sirtuin-3 (SIRT3) (K_d=2.756 μM), antagonizes Isoproterenol/ISO (HY-B0468)-induced cytotoxicity. 2-APQC activates the SIRT3-PYCR1 axis to enhance mitochondrial proline metabolism and inhibit the ROS-p38MAPK pathway by inhibiting signaling pathways such as mTOR-p70S6K, JNK, and TGF-β/Smad3. 2-APQC also activates the AMPK-Parkin axis to alleviate myocardial hypertrophy and fibrosis and protect cardiac function. 2-APQC can be used in the study of heart failure.

Phellopterin, an orally active furocoumarin with multiple biological activities. Phellopterin is a partial agonist of the central benzodiazepine receptors. Phellopterin exerts anti-inflammatory effects by upregulating SIRT1, downregulating ICAM-1 (reducing chronic inflammation, aiding diabetic ulcer healing), inhibiting STAT3 phosphorylation (easing atopic dermatitis inflammation), regulating Akt/PKC pathways (lowering TNF-α-induced VCAM-1 to block monocyte adhesion), and inhibiting TLR4/NF-κB pathway and macrophage M2 polarization (alleviating colitis-related cancers). Phellopterin suppresses ovarian cancer progression via inhibiting the PU.1/CLEC5A/PI3K-AKT loop (inducing cell cycle arrest, apoptosis, DNA damage). Phellopterin alleviates murine diabetes by promoting adipocyte differentiation and increasing PPARγ. Phellopterin also has anti-HSV-1 activity. Phellopterin can be used for studying anti-inflammation, anti-cancer (e.g., ovarian cancer, colitis cancer), blood glucose lowering, anti-diabetes, and anti-virus.

SKLB-11A is a selective, orally active and allosteric SIRT3 (sirtuin 3) agonist with a K_d value of 4.7 μM. SKLB-11A is highly selective for other members of the SIRT family. SKLB-11A activates autophagy-related signaling pathways, prevents mitochondrial dysfunction, improves cardiac function in Doxorubicin (HY-15142A)-induced cardiotoxicity and myocardial ischemia/reperfusion models.