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HH-F3

Development stage: Preclinical
Lead developer: National Taiwan University
Modality: Metabolically Activated Prodrugs → Prodrugs/Conditional Activator Small Molecules → Small Molecules, Classical Binding Small Molecules → Small Molecules
Administration: Oral

Overview

HH-F3 is a bioactive fraction derived from the medicinal herb *Graptopetalum paraguayense* (GP), characterized as being rich in condensed tannins, specifically polymeric proanthocyanidins. It is primarily investigated for the treatment of hepatocellular carcinoma (HCC) and liver fibrosis. HH-F3 exerts its anti-cancer effects by suppressing the expression of oncogenic proteins such as Aurora kinase A (AURKA), Aurora kinase B (AURKB), and FLJ10540 at the translational level. Mechanistically, it induces apoptosis through the intrinsic mitochondrial pathway, involving the production of reactive oxygen species (ROS) and the loss of mitochondrial membrane potential. Furthermore, HH-F3 modulates the PI3K/PTEN/AKT signaling pathway by up-regulating PTEN expression and inhibiting AKT phosphorylation at Ser473. Preclinical studies have demonstrated that HH-F3 can synergize with sorafenib to inhibit HCC cell proliferation and reduce tumor burden and hepatic collagen content in animal models.

Other names: Graptopetalum paraguayense fraction HH-F3GP fraction HH-F3

Targets

AKT (RAC-alpha serine/threonine-protein kinase)AURKB (Aurora kinase B)AURKA (Aurora kinase A)CEP55 (Centrosomal protein of 55 kDa)

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