PNR-7-02 

PNR-7-02 is a dual Rev1 and human DNA polymerase η (hpol η) inhibitor, with an IC₅₀ value of 8 μM against hpol η. PNR-7-02 binds to hpol η to disrupt the orientation of template DNA and block the catalytic function of hpol η. When used in combination with Cisplatin (HY-17394), PNR-7-02 induces DNA damage and replication stress in cells with intact hpol η function. PNR-7-02 can be used in mechanism studies related to chronic myeloid leukemia and ovarian cancer^[1][2].

PNR-7-02 inhibits human Pol η function by binding its little finger domain and synergizes with Cisplatin (HY-17394) to kill chronic myeloid leukaemia and ovarian cancer cell lines^[1].
PNR-7-02 potently inhibits purified hpol η with an IC₅₀ of 8 μM in a fluorescence-based activity assay^[2].
PNR-7-02 (8-24 μM; 5 min) inhibits purified hpol η, hRev1, and hpol λ with equal potency (IC₅₀ = 8 μM) and is 3-fold less potent against hpol κ^[2].
PNR-7-02 (20-100 μM; 10-60 min) binds to purified hpol η near the little finger domain's L-helix, protecting Arg351 from HPG modification, and induces conformational changes in the palm domain at high concentrations^[2].
PNR-7-02 acts synergistically with CDDP to reduce viability in hpol η-proficient HAP-1 cells (CI = 0.47-0.59) but does not affect CDDP sensitivity in hpol η-deficient HAP-1 cells; PNR-7-02 alone has EC₅₀ values of 4.6 μM and 5.6 μM in hpol η-proficient and -deficient cells, respectively^[2].
PNR-7-02 (0.1-1 μM) enhances CDDP-induced γH2AX formation (a marker of DNA damage/replication stress) by ~3-fold in hpol η-proficient HAP-1 cells^[2].

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

445.92

C₂₄H₁₆ClN₃O₂S

1633660-76-0

Solid

Light yellow to yellow

O=C1NC(NC(/C1=C\C2=CN(CC3=CC4=C(C=CC=C4)C=C3)C5=C2C=C(Cl)C=C5)=O)=S

Room temperature in continental US; may vary elsewhere.

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

• [1]. Ler AAL, et al. DNA Damage Tolerance Pathways in Human Cells: A Potential Therapeutic Target. Front Oncol. 2022;11:822500. Published 2022 Feb 7.  [Content Brief]

  [2]. Zafar MK, et al. A Small-Molecule Inhibitor of Human DNA Polymerase η Potentiates the Effects of Cisplatin in Tumor Cells. Biochemistry. 2018;57(7):1262-1273.