PARP/PI3K-IN-1

PARP/PI3K-IN-1 (compound 15) is a potent PARP/PI3K inhibitor with pIC50 values of 8.22, 8.44, 8.25, 6.54, 8.13, 6.08 for PARP-1, PARP-2, PI3Kα, PI3Kβ, PI3Kδ, and PI3Kγ, respectively. PARP/PI3K-IN-1 is a highly effective anticancer compound targeted against a wide range of oncologic diseases[1].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> Epigenetics >> PARP

Signaling Pathways >> PI3K/Akt/mTOR >> PI3K

Signaling Pathways >> Cell Cycle/DNA Damage >> PARP

PARP-1:8.22 (pIC50)

PARP-2:8.44 (pIC50)

PI3Kα:8.25 (pIC50)

PI3Kδ:8.13 (pIC50)

PI3Kγ:6.08 (pIC50)

PI3Kβ:6.54 (pIC50)

PARP/PI3K-IN-1 (compound 15; 1 μM; 72 hours) leads to a significant increase in cell apoptosis[1]. PARP/PI3K-IN-1 (1 μM; 72 hours) reduces the autophosphorylation levels of AKT and S6 while increases the autophosphorylation level of ERK after treating cells, indicating that it can inhibit the PI3K pathway and activate the ERK pathway[1]. PARP/PI3K-IN-1 (1 μM) displays a strong capability to downregulate the expression of BRCA1/2 at the mRNA level in MDA-MB-468 cancer cells[1]. PARP/PI3K-IN-1 not only shows significant inhibitory activity against BRCA-deficient cells HCC1937 and HCT116, but also displays potent anti-proliferative activity against BRCA-proficient cells MDA-MB-231 and MDA-MB-468[1]. Apoptosis Analysis[1] Cell Line: MDA-MB-468 cancer cells Concentration: 1 μM Incubation Time: 72 hours Result: Led to a significant increase in cell apoptosis. Western Blot Analysis[1] Cell Line: MDA-MB-468 cancer cells Concentration: 1 μM Incubation Time: 72 hours Result: Reduced the autophosphorylation levels of AKT and S6 while increased the autophosphorylation level of ERK after treating cells.

PARP/PI3K-IN-1 (i.p.; 50 mg/kg; twice daily (BID) for 34 consecutive days) significantly suppresses the tumor growth[1]. Animal Model: Six-week-old male BALB/c nude mice with MDA-MB-468 cells[1] Dosage: 50 mg/kg Administration: i.p.; twice daily (BID) for 34 consecutive days Result: Significantly suppressed the tumor growth.

[1]. Wang J, et al.Discovery of Novel Dual Poly(ADP-ribose)polymerase and Phosphoinositide 3-Kinase Inhibitors as a Promising Strategy for Cancer Therapy.J Med Chem. 2020 Jan 9;63(1):122-139.