The Centre for Drug Candidate Optimisation (CDCO) was established in 2003 to fill a critical gap in drug discovery by providing translational expertise on absorption, distribution, metabolism and excretion (ADME) and pharmacokinetic (PK) properties of investigational drug candidates. Identifying PK liabilities during drug discovery is essential to guide appropriate structural modifications and identify strategies to mitigate risks during development.
Year of Establishment: 2003
Access and Pricing:
The CDCO provides expertise and infrastructure to non-commercial and commercial users, with costs dependent on the specific arrangement (fee for service, collaboration, or another model). Reduced rates are available for longer-term projects.
The identity of many of CDCO’s industry collaborators and their specific programs is protected by commercial-in-confidence agreements; however some companies have agreed to be publically named as collaborators including Biota, Bionomics, Prana Biotechnology, the CRC for Cancer Therapeutics, the Medicines for Malaria Venture (Geneva) and the Drugs for Neglected Diseases initiative (Geneva). Over the past 10 years, the CDCO has collaborated with many Australian biotech start-up companies, and maintains close links with companies with the biotech community. The CDCO has contributed to Australian and international drug discovery programs that have progressed more than 20 drug candidates into clinical trials. Several significant, long term collaborations include:
- Medicines for Malaria Venture: The CDCO and Prof Susan Charman have maintained a long term collaborative relationship with the Medicines for Malaria Venture (MMV, Geneva), with continued funding for over 13 years. Through this collaboration the CDCO has contributed to one new drug product being registered in India (Synriam™), two drug candidates currently in clinical development (OZ439 and DSM265), and three candidates currently in preclinical development. This work has led to a number of scientific publications in journals such as Nature, PNAS, Sci Trans Med, and J Med Chem, among others.
- Synriam™: approved antimalarial drug marketed in India that arose through a drug discovery collaboration between Monash (CDCO), the University of Nebraska, Swiss Tropical and Public Health Institute, Roche and MMV. The team delivered the first-ever synthetic peroxide into clinical trials, and the drug is currently being used to treat uncomplicated malaria in India.
- OZ439 – Collaboration between Monash (CDCO), the University of Nebraska, Swiss Tropical and Public Health Institute, Roche and MMV that discovered the first-ever long half-life synthetic peroxide with the potential to provide a single dose cure of malaria; this compound is currently in Phase II clinical trials.
- DSM265: Collaboration between Monash (CDCO), University of Texas Southwestern Medical Centre, University of Washington and MMV that discovered an antimalarial compound with a novel mechanism of action against parasite dihydroorotate dehydrogenase; the candidate is currently in Phase I clinical trials.
- Drugs for Neglected Diseases initiative: The CDCO has developed a very successful relationship with the Drugs for Neglected Diseases initiative (DNDi, Geneva) collaborating since 2007, first through the Chagas Lead Optimisation Consortium and currently through the Australian Lead Optimisation Consortium in partnership with Epichem Pty Ltd (Perth), Griffith University, and the London School of Hygiene and Tropical Medicine.
Main contact: Susan Charman (Director) or Andrew Powell (Operations Manager)
Email: firstname.lastname@example.org email@example.com
Phone: +61 (0)3 9903 9626 +61 (0)3 9903 9149
|LC/MS instruments (single and quadruple MS; time of flight MS) coupled with UPLCs
||Quantitative bioanalysis, metabolite identification, physicochemical profiling
||Preclinical formulation development
|Automated liquid-handling robot
||Screening studies for kinetic solubility, metabolic stability, and CYP inhibition
|Automated small animal in vivo blood sampling using BASI Culex ™
||In vivo assessment of drug absorption, bioavailability, distribution, brain penetration and pharmacokinetics
|In silico and in vitro methods for profiling physiochemical properties
||Assessment of solubility, partitioning, ionisation properties, stability, solid state properties
|Plate-based assays for CYP450 metabolic stability, metabolite profiling and metabolic drug interactions
||Metabolic stability in hepatic microsomes and hepatocytes from various species
|Cell culture facilities for permeability assessment, role of efflux and transported proteins
||Permeability studies using Caco-2 and MDCK cells
|In vitro methods for binding, distribution and stability
||Binding to plasma proteins and proteins present in in vitro media, distribution between red blood cells and plasma, stability in blood and plasma