HSP90α-IN-1 is an HSP90α inhibitor (IC50= 111 nM) that demonstrates anti-aging activity across various cellular senescence models. Belonging to the xanthine family, HSP90α-IN-1 is involved in research focused on combating age-related inflammation, senescence, and diseases (including cancer), and it may contribute to extending healthy lifespan.

HSP90 α:111 nM

HSP90α-IN-1 (Compound K5) displays the highest anti-aging activity in senescent PD15 and PD19 cell lines at 1 μM for 48 hours, while maintaining substantial safety in non-senescent cells. It inhibits HSP90α in a dose-dependent manner with an IC50 of 111 nM at concentrations ranging from 1 pM to 10 μM over 48 hours. At a concentration of 500 nM, HSP90α-IN-1 exhibits significant anti-aging effects on senescent IMR90 (PD22) (EC50 = 380 nM) and WI38 (PD51) (EC50 = 650 nM) cells with no significant toxicity when applied at 0.1-200 μM for 48 hours. Additionally, HSP90α-IN-1 induces apoptosis in senescent IMR90 cells (PD21) at 25 μM for 48 hours. In TAM-treated MCF7 cell lines, HSP90α-IN-1 (10 μM, 24-96 hours) reduces SA-β-galactosidase staining and increases the mortality rate of senescent cells, showing anti-aging effects with an EC50 of 24.4 μM while displaying low cytotoxicity towards proliferating cells (EC50 = 167.2 μM).

HSP90α-IN-1 (Compound K5), administered via dietary supplementation with fresh food replacement three times weekly at concentrations of 10-100 μg/mL, extends the average lifespan of wild-type Canton-S fruit flies (n = 884) by 6.63%. Additionally, HSP90α-IN-1 at 10 μg/mL, delivered through intraperitoneal injection over three consecutive days, significantly reduces senescent cell burden in P16-3MR mice.