PZL-A 

PZL-A is a activator of mitochondrial DNA (mtDNA) synthesis. PZL-A restores wild-type-like activity to mutant forms of polymerase γ (POLγ) with AC₅₀ s of 160 and 20 nM for A467T and G848S. PZL-A activates mtDNA synthesis in cells, enhancing biogenesis of the oxidative phosphorylation machinery and cellular respiration. PZL-A is promising for relieving POLG disease and other severe conditions linked to depletion of mtDNA^[1].

PZL-A (0-100 μM, 10 min) dose-dependently activates the mutants (R232H, A467T, G848S, and W748S) (AC₅₀: 20-200 nM), stabilizes the interaction with template, and interacts directly with the POLγ holoenzyme with increase of unfolding temperature^[1].
PZL-A (1 μM, 0-15 min) stimulates DNA synthesis and enhances the rate of dNTP incorporation in mutants (R232H, A467T, G848S and W748S) without influence on exonuclease activity across a broad range of dNTP concentrations (0.08-10 µM)^[1].
PZL-A (10 μM) interacting directly with the POLγ holoenzyme and increasing the unfolding temperature in mutants (R232H, A467T, G848S and W748S)^[1].
PZL-A binds to a hydrophobic pocket between POLγA and POLγB with a C-shaped orientation, and the site is generally unaffected by most disease-causing mutations^[1].
PZL-A (10 μM, 7.5-60 min) has a marked stimulatory effect, leading to DNA synthesis of longer double-stranded DNA (dsDNA) products ^[1].
PZL-A (1-3 μM, 7-14 days) strongly stimulates mtDNA repopulation rates with good tolerance in A467T/G848S and W748S/R232H mutant fibroblasts as well as quiescent fibroblasts^[1].
PZL-A (0.00001-10 μM, 5-10 days) dose-dependently stimulates full-length mtDNA repopulation and increases 7S DNA levels in A467T/G848S and W748S/R232H mutant fibroblasts^[1].
PZL-A (0.02-1 μM, 7-10 days) increases mtDNA levels and ameliorates OXPHOS activity in A467T/G848S and W748S/R232Hmutant fibroblasts and G848S/G848S mutant NSCs^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

368.82

C₁₉H₁₇ClN₄O₂

3068830-89-4

ClC1=CC=CC2=C1OCC[C@@H]2NC(NC3=NN(C4=CC=CC=C4)C=C3)=O

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Valenzuela S, et al. Small molecules restore mutant mitochondrial DNA polymerase activity. Nature. 2025 Jun; 642(8067):501-507.  [Content Brief]