At NUVISAN, we understand the importance of developing a strong preclinical candidate. Decades of experience in the big-pharma industry in combination with cutting-edge technologies allow us to successfully optimize your lead molecule in preparation for preclinical development. This is effectively achieved by close collaboration between our medicinal chemists, computational compound designers, discovery pharmacologists (in vitro, ex vivo, in vivo studies, and DMPK experts (DMPK property optimization).

Lead Optimization

Your drug development campaign will benefit from our strong drug-hunting attitude in the lead-to-candidate process. Our state-of-the-art methodologies (e.g., photochemistry, electrochemistry, final-stage diversification) facilitate quick synthesis of your target compounds. As our client, you benefit from fast, automated, and customized purification of drug candidates and intermediates. As a result, you receive a multi-dimensional lead optimization program with short cycle times. Routinely, we measure and interpret crucial physicochemical parameters for your lead compounds. Most importantly, our lead optimization process is an interdisciplinary team effort, supported by insights from our rich life science database and our Digital Life Science team with minimal effort on your part.

ADME Optimization In Vitro and In Vivo

During lead optimization, the goal is to guide a focused and fast optimization of lead structures toward a viable preclinical candidate. A tailor-made screening tree is a critical step for identifying and potentially overcoming ADME liabilities as quickly as possible.

Initially, state-of-the-art in vitro ADME assays are performed, which means the characterization of metabolic stability (liver microsomes and hepatocytes), permeability (Caco-2 assay), plasma protein binding (different species), CYP profile (inhibition and induction), metabolite identification, and phenotyping of drug metabolizing enzymes (CYPs, UGTs, and non-CYPs). Some of our assays can be performed as high-throughput and can be tailored to your needs.

These thorough investigations facilitate and complement the identification of suitable compounds for in vivo pharmacodynamic and pharmacokinetic (PK) studies. Depending on your compound profile and needs, in vivo study designs are optimized by our DMPK experts. Each of our different study designs (e.g., with regard to a variety of available administration routes, different sampling technologies, or mono/cassette dosing) is performed using state-of-the-art methodologies. High animal welfare standards that align with the 3R-concept and AAALAC accreditation are the basis of our work. Furthermore, tailor-made studies for specific ADME questions can be provided, such as tissue distribution or elimination studies (including renal and hepatic drug clearance). Finally, the test of different formulations to identify the best formulation for other in vivo studies is our expertise.

Mode-of-Action Characterization

We can help you to de-risk your project through gathering detailed insights into the mode-of-action (MoA) of your candidate molecules by ensuring on-target activity—from validation of drug–target interaction to efficacy assessments. We identify target engagement and pharmacodynamic biomarkers based on well-defined studies of the target biology using literature searches as well as bioinformatic analyses. Using in silico tools, big data mining, database screening, extraction, and assembly, we identify pathway–disease relations and entity recognitions, and we scrutinize your target and its signaling pathways. In addition, we help you identify pathomechanisms that offer therapeutic rationales with optimum fit to your compound.

Efficacy Through In Vivo Models

Dedicated to the optimization of your lead series, we offer support in assessing their efficacy through in vivo models with respect to potency, selectivity, and PK properties. NUVISAN offers a large panel of disease models across multiple indications. Using AP-MALDI HRMS, we can help you understand the distribution and regional concentrations of your candidate drugs in any type of tissue section.

Our lead-to-candidate solutions cover: