Ribociclib (LEE011) – a cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor
CDK4/6 controls the entry into cell cycle progression and its activation leads to cell proliferation in tumors.3,4 LEE011, a selective CDK4/6 inhibitor, is currently in Phase I development.
PIM447 (formerly LGH447) – a PIM inhibitor
PIM kinases play a role in cell cycle progression, cell survival and tumorigenesis, and elevated levels of PIM1 and PIM2 are frequently found in cancer tissue samples from patients with several hematologic malignancies.5,6 PIM447 is being developed as a PIM inhibitor.
WNT974 – a Porcupine inhibitor
Porcupine is an enzyme required for the function and secretion of Wingless-type (Wnt) ligands.7 Activation of the Wnt pathway regulates, for example, cell proliferation, migration, apoptosis, and differentiation.8,9 WNT974 is under development for the treatment of cancers that are driven by the Wnt pathway in a Wnt ligand-dependent manner.
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Vince JE, Wong WW, Khan N, et al. IAP antagonists target cIAP1 to induce TNF-alpha-dependent apoptosis. Cell. 2007;131(4):682-693.
Ortega S, Malumbres M, Barbacid M. Cyclin D-dependent kinases, INK4 inhibitors and cancer. Biochim Biophys Acta. 2002 Mar 14;1602(1):73-87.
Shapiro GI. Cyclin-dependent kinase pathways as targets for cancer treatment. J Clin Oncol. 2006;24(11):1770-1783.
Nawijn MC, Alendar A, Berns A. For better or for worse: the role of Pim oncogenes in tumorigenesis. Nat Rev Cancer. 2011;11(1):23-34.
Brault L, Gasser C, Bracher F, et al. PIM serine/threonine kinases in the pathogenesis and therapy of hematologic malignancies and solid cancers. Haematologica. 2010;95(6):1004-1015.
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Turashvili G, Bouchal J, Burkadze G, et al. Wnt signaling pathway in mammary gland development and carcinogenesis. Pathobiology. 2006;73(5):213-223.
All compounds are either investigational or studied in new indications. Efficacy and safety have not been established. There is no guarantee that they will become commercially available.