Ardea Biosciences, Inc. presented data demonstrating the potent activity and favourable pharmacokinetic profile of the company's mitogen-activated ERK kinase (MEK) inhibitor family of compounds in the treatment of cancerous tumours.
The data showed that RDEA119 and RDEA436 are potent inhibitors of MEK1/2, an important step in cell cycle regulation. Both compounds suppress tumour cell growth in vitro and in vivo, have significant anti-inflammatory activity, and have limited potential for central nervous system (CNS) toxicity, a problem for other members of this class. RDEA119 is currently in phase 1 clinical studies in advanced cancer patients and healthy volunteers for assessment of its ability to inhibit inflammatory cytokines.
Preliminary phase 1 data have demonstrated that RDEA119 has a long half-life and favourable pharmacokinetic properties, allowing for once daily oral dosing. In addition, the doses being evaluated in the phase 1 study have achieved systemic exposure consistent with active doses in animal models of human tumours, without drug-related toxicity. Data from a human micro-dose trial, produced by Vitalea Science, Inc. using Accelerator Mass Spectrometry (AMS) technology, demonstrated that RDEA436 also has a long half-life and favourable pharmacokinetic properties.
"MEK inhibitors may have broad utility in the treatment of human cancers and inflammatory diseases. We are pleased to have two compounds in this class, both with excellent preclinical profiles and promising human pharmacokinetics, moving forward in clinical development," said, Barry D. Quart, PharmD, president and CEO, Ardea Biosciences. "We constantly strive to diminish the inherent risk of drug development by having multiple compounds, from structurally different chemical classes, moving through development and we are excited to complete phase 1 testing of our lead MEK inhibitor, RDEA119, and progress RDEA436 into PHASE 1 clinical testing, in the second half of 2008."
RDEA119 and RDEA436, non-ATP competitive, highly-selective MEK inhibitors for the treatment of cancer and inflammatory diseases, are two of the compounds from Ardea's MEK inhibitor research and development program. RDEA119 has shown potential as a potent and selective inhibitor of MEK, which is believed to play an important role in cancer cell proliferation, apoptosis and metastasis.
Preclinical and clinical results suggest that RDEA119 has favourable properties, including oral dosing, excellent selectivity and limited retention in the brain, which, in turn, may result in a reduced risk of central nervous system (CNS) side effects. Preclinical data shows that RDEA436 is a potent in vitro and in vivo inhibitor of MEK, has favourable pharmacokinetic properties with low CNS penetration and a long half-life in a human micro-dose study indicating the potential for once daily dosing in humans.