ADPM06, an azadipyrromethene compound, is a new nonporphyrin photodynamic therapeutic (PDT) agent with potential as a lead candidate. It demonstrates significant IC50 values in the micro-molar range in human tumor cells, as well as inducing apoptosis.

The effectiveness of ADPM01 is completely nullified at a 1% oxygen level in HeLa and MRC5 cell lines. Conversely, ADPM06 shows only a slight decrease in its light-activated functionality under low oxygen (hypoxic) conditions compared to normal oxygen (normoxic) levels[1]. The photochemical therapy with ADPM06 (ADPM06-PDT) triggers both endoplasmic reticulum (ER) stress and the unfolded protein response, leading to apoptosis through the activation of caspases[2]. Additionally, ADPM06-PDT promotes a rapid, spliceosome-independent splicing of XBP1 mRNA by activated inositol-requiring enzyme 1 (IRE1), illustrating a post-transcriptional modification. This apoptosis induced by ADPM06-PDT is also characterized by the production of reactive oxygen species (ROS)[2]. In a Cell Viability Assay conducted on HeLa and MRC5 cell lines at concentrations ranging from 1 nM to 100μM and an incubation time of 24 hours, ADPM06 maintained significant effectiveness, exhibiting half-maximal effective concentration (EC50) values of 1.5 and 1.6 × 10?6 M for HeLa and MRC5 cells, respectively[1].

ADPM06-PDT has initiated apoptosis and triggered an ER stress response in vivo[2]. It is well-tolerated and demonstrates significant complete response rates across diverse cancer models with a short drug-light interval[2]. In female Balb C nu/nu mice[2], a dosage of 2 mg/kg in a 0.3 mL solution was administered intravenously via the lateral tail vein, leading to a rapid decrease in tumor-specific luciferase activity within 1 hour post-PDT, with further reduction observed 4 hours post-PDT.