POLQ-IN-2

POLQ-IN-2 (compound 37) (10 μM-0.51 nM; 6 days; WT DLD-1 endpoint at day 7, BRCA2^−/− DLD-1 endpoint at day 12) preferentially inhibits BRCA2^−/− DLD-1 cell proliferation (IC₅₀ = 0.058 μM), while its effect on WT DLD-1 cells is weaker (IC₅₀ = 3.9 μM)^[1].
POLQ-IN-2 (7-14 day dose range) selectively reduces clonogenic survival of HRR-deficient DLD-1 BRCA2^-/-, SKOV3 BRCA2 KO, SKOV3 PALB2 KO, and SNU601 cells, with an IC₅₀ of 0.022 µM in DLD-1 BRCA2^-/- versus 8.9 µM in DLD-1 WT^[1].
POLQ-IN-2 (7-14 day dose range) combined with Olaparib produces higher HSA synergy scores in HRR-deficient models, such as Capan-1 (74.10) and MDA-MB-436 RAD51B LacZ (62.03), while the scores are lower in HRR-proficient controls, such as SKOV3 WT (0.34) and MDA-MB-436 RAD51B + BRCA1 WT (3.28)^[1].

POLQ-IN-2 (compound 37) (12 concentration points; incubation 20 min-1 h) is a potent inhibitor of the isolated POLQ polymerase domain, with IC₅₀ < 0.003 μM^[1].
POLQ-IN-2 (100 μM) shows much higher selectivity for POLQ than for DNA polymerases α, γ, η, and ν^[1].
POLQ-IN-2 inhibits POLQ-dependent MMEJ pathway activity in HEK293T cells with an IC₅₀ of 0.10 μM^[1].
POLQ-IN-2 exhibits specific antiproliferative activity in the HRR-deficient background, with an IC₅₀ of 0.022 μM in DLD-1 BRCA2^−/− and 0.015 μM in SNU601^[1].
POLQ-IN-2 (0-10000 nM; Olaparib 1-100 nM) exhibits synergy with Olaparib in SKOV3 PALB2 KO cells (HSA synergy score 31.17), whereas no synergy occurs in SKOV3 WT cells (score 0)^[1].
POLQ-IN-2 is a potent inhibitor of the POLQ polymerase domain, with pIC₅₀ > 8.5^[1].
POLQ-IN-2 shows higher potency in BRCA2^-/- DLD-1 cells (pIC₅₀ = 7.24) than in WT DLD-1 cells (pIC₅₀ = 5.41)^[1].
POLQ-IN-2 (1 µM AZD7648 (HY-111783) and multiple concentrations, 24-72 h) inhibits MMEJ in HEK293T cells with a pIC₅₀ of 6.98^[1].