Cylene: Products

Product Pipeline

Cylene is using its unique discovery platforms to design and develop small molecule drugs that selectively target cancer cells. Cylene’s Serine/Threonine kinase inhibitor platform has created inhibitors of CK2 and the PIM family of kinases. There is considerable evidence supporting a multifunctional role of CK2 in many cellular events contributing to the cancer phenotype, making it an attractive target in a variety of hyperproliferative diseases, such as cancer. The PIM kinases are key regulators in many signaling pathways implicated in cancer. RNA Polymerase I (Pol I) inhibitors directly disrupt the function of the nucleolus which is abnormal in cancer cells. Hallmarks of cancer include excessive cellular proliferation, deregulated signaling, and abnormalities of the nucleolus. Mutations in signaling pathways lead to excessive ribosome synthesis in the nucleolus in order to support excessive protein synthesis that is required for cell growth and proliferation of cancer cells. Nucleolus Targeting Agents have been created with enhanced specificity and safety profiles to selectively kill cancer cells. Cylene’s proprietary technologies and approaches to creating Pol I inhibitors and novel Serine/Threonine kinase inhibitors are unique in the industry and are delivering a pipeline of potent and well-tolerated anticancer agents.

Oral CX-4945

CX-4945 is a small molecule that has been optimized to selectively inhibit CK2 activity and is the first agent in class to enter the clinic. The CK2 protein kinase plays a multifunctional role in cell cycle regulation, signal transduction, transcriptional control, angiogenesis, apoptosis and inflammation. Because CK2 contributes to the cancer phenotype via multiple cellular events, CX-4945 has been designed with the objective of creating a multifunctional inhibitor by targeting a single protein and affecting potentially many cancers. CX-4945 demonstrates broad spectrum anti-proliferative activity against diverse cancer cell lines, has potent inhibition of CK2 and the data attribute the anti-tumor activity of CX-4945 to intracellular inhibition of the CK2 enzyme. CX-4945 is currently in a dose-escalating Phase I trial at multiple sites in the US, during which a series of validated biomarkers will be evaluated. CK2-driven cancers will be evaluated in the Phase I trial (include breast, prostate, pancreas cancers and inflammatory breast cancer), as well as multiple myeloma and Castleman’s Disease.

Oral PIM Kinase Inhibitors

Cylene’s expertise in novel chemistry and drug discovery led to its PIM inhibitor program, which has produced CX-6258 and other preclinical stage oral drug candidates.

Quarfloxin (CX-3543)

Quarfloxin is a ground-breaking small-molecule targeted cancer therapeutic derived from the validated fluoroquinolone class of drugs. Rationally designed to selectively inhibit ribosomal RNA (rRNA) biogenesis in cancer cells, quarfloxin disrupts the interaction between the Nucleolin protein and a G-quadruplex DNA structure in the ribosomal DNA (rDNA) template, a critical interaction for rRNA biogenesis and one that is amplified in cancer cells. As a result, quarfloxin selectively knocks out a critical source of support for cancer cells and induces apoptotic cell death in cancers. Many commercialized cancer therapeutics act indirectly on rRNA Biogenesis through upstream modulators, but quarfloxin is the first agent to directly target this cancer-specific aberrant cell function. Quarfloxin is currently in Phase II development for the treatment of carcinoid/neuroendocrine tumors (C/NET), and trials are being conducted at multiple top tier clinical sites throughout the US.

Oral CX-5461

CX-5461 arose from an intense program to create orally active small molecules that inhibit the RNA Polymerase I activity in the nucleolus but not RNA Polymerase II that synthesizes mRNA. CX-5461 induces autophagy in cancer cells, demonstrates favorable PK/ADMET and safety properties and exhibits potent antitumor activity in murine xenograft models. This novel small molecule is in late preclinical development.