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 efficacy of ADPM01 is completely ablated at a 1% oxygen level in Hela and MRC5 cell lines. ADPM06 displays only a partial reduction in light-induced activity in hypoxic as compared to normoxic conditions[1]. ADPM06-PDT induces ER stress and unfolded protein response[2]. ADPM06-PDT induces apoptosis and involves caspase enzymatic activity[2]. Following ADPM06-PDT, a rapid processing of XBP1 mRNA occurs resulting in the removal of an intron from the mRNA in a spliceosome-independent manner, a post-transcriptional modification catalyzed by the action of activated inositol-requiring protein 1 (IRE1)[2]. ADPM06-PDT-induced apoptosis involves the generation of ROS[2]. Cell Viability Assay[1]Cell Line: Hela and MRC5 cell lines. Concentration: 1 nM - 100μM. Incubation Time: 24 h. Result: Retained considerable efficacy, with EC 50 values of 1.5 and 1.6 × 10 ?6 M for HeLa and MRC5 cells, respectively.

ADPM06-PDT has revealed an initiation of apoptosis in vivo, as well as induction of an ER stress response[2]. ADPM06-PDT is well tolerated in vivo and elicits impressive complete response rates in various models of cancer when a short drug-light interval is applied[2]. Animal Model: Female Balb C nu/nu mice[2]. Dosage: 2 mg/kg in 0.3 mL solution via the lateral tail vein. Administration: IV. Result: Revealed a rapid reduction in tumor-specific luciferase activity as early as 1-hr post-PDT, with levels decreasing further 4-hr post-PDT.