4-[(E)-2-(4-methoxyphenyl)diazenyl]-1H-pyrazole-3,5-diamine

ILK-IN-3 is an orally active integrin linked kinase (ILK) inhibitor. ILK-IN-3 improves the anticancer efficacy of Docetaxel (HY-B0011) in orthotopic LCC6 model[1][2].

QLT0267 is an orally active, potent and selective integrin-linked kinase (ILK) inhibitor (IC50 = 26 nM; selectivity: >1000-fold over CK2, CSK, DNA-PK, PIM1, PKB/AKT, PKC, >100-fold over ERK1, GSK3β, LCK, PKA, p70S6K, and RSK1/QLT, >10-fold over CDK1/2/5) th at inhibits ILK-dependent cellular signaling (IC50 in 2h = 1 μM against 20 nM EGF-induced pAKT Ser473 phosphorylation in Hth74 cells). QLT0267 treatment causes thyroid cancer cell cycle arrest and apoptosis, leading to anti-proliferation efficacy in cultures (IC50 <6 μM; NPA187, DRO, and K4 cell lines) and in mice in vivo (DRO xenografts-derived tumor growth; 50-100 mg/kg via daily p.o.).

DYRK1

[1] Jessica Kalra, et al. Validating the Use of a Luciferase Labeled Breast Cancer Cell Line, MDA435LCC6, as a Means to Monitor Tumor Progression and to Assess the Therapeutic Activity of an Established Anticancer Drug, Docetaxel (Dt) Alone or in Combination With the ILK Inhibitor, QLT0267. Cancer Biol Ther. 2011 May 1;11(9):826-38. DOI:10.4161/cbt.11.9.15183
[2] Mavrogeni ME, et al. A facile consensus ranking approach enhances virtual screening robustness and identifies a cell-active DYRK1α inhibitor. Future Med Chem. 2018 Oct;10(20):2411-2430. DOI:10.4155/fmc-2018-0198