Safety, Tolerability, and Pharmacokinetics of an Oral Small Molecule Inhibitor of IL-17A (LY3509754): A Phase I Randomized Placebo-Controlled Study.

For some patients with psoriasis, orally administered small molecule inhibitors of interleukin (IL)-17A may represent a convenient alternative to IL-17A-targeting monoclonal antibodies. This first-in-human study assessed the safety, tolerability, pharmacokinetics (PKs), and peripherally circulating IL-17A target engagement profile of single or multiple oral doses of the small molecule IL-17A inhibitor LY3509754 (NCT04586920). Healthy participants were randomly assigned to receive LY3509754 or placebo in sequential escalating single ascending dose (SAD; dose range 10-2,000 mg) or multiple ascending dose (MAD; dose range 100-1,000 mg daily for 14 days) cohorts.

ERK Inhibitor LY3214996 Targets ERK Pathway-Driven Cancers: A Therapeutic Approach Toward Precision Medicine.

The ERK pathway is critical in oncogenesis; aberrations in components of this pathway are common in approximately 30% of human cancers. ERK1/2 (ERK) regulates cell proliferation, differentiation, and survival and is the terminal node of the pathway. BRAF- and MEK-targeted therapies are effective in BRAF V600E/K metastatic melanoma and lung cancers; however, responses are short-lived due to emergence of resistance.