Pygenic acid A is a natural compound from Prunella vulgaris and PD-1/PD-L1 inhibitor, directly binds to the PD-1 downstream signaling molecule SHP-2 with SPR KD of 0.82 uM, inhibiting the recruitment of SHP-2 by PD-1, promotes the immune response.
Pygenic acid A is a potent and safe intracellular checkpoint-targeting adjuvant capable of potentiating both cellular immunity and cross-protective humoral immunity.
Pygenic acid A not only induced apoptosis but also sensitized the metastatic triple-negative breast cancer cell lines, MDA-MB-231 cells (human) and 4T1 cells (mouse), to anoikis.
Pygenic acid A downregulated the pro-survival proteins, including cIAP1, cIAP2, and survivin, leading to cell death of both attached and suspended cells.
Pygenic acid A decreased the levels of proteins associated with anoikis resistance, including p21, cyclin D1, p-STAT3, and HO-1.
Pygenic acid A activated ER stress and autophagy, as determined by increases in the levels of characteristic markers, such as IRE1α, p-elF2α, LC3B I, and LC3B II, PA treatment resulted in p62 accumulation.