Transporter Profiling Services

Transporter Profiling Services for Preclinical Candidate Selection and Mechanism of Action (MOA) Identification

Optivia offers comprehensive transporter profiling services and specialized transporter panels to help you select drug candidates with desirable transporter-interaction profiles, elucidate MOA of off-target clinical responses, and enhance the commercial potential of your drugs through identifying potential new therapeutic indications.

Opti-DDI™ Panel Select and optimize preclinical candidates with less DDI liability
Opti-Target™ Panel Profile of therapeutic transporter targets for studying the MOA of off-target clinical outcomes and for identifying new therapeutic indications for approved or experimental drugs
Opti-Safety ™ Panel Identify safety liabilities of preclinical candidates by avoiding undesirable interactions with toxicity related transporters
Opti-ADME™ Panel Elucidate key ADME pathways and determinants for predicting the pharmacological attributes of preclinical candidates    d tissue targeting

 Transporter Profiling Services – Key Features

  • Turn-key solution with fast turnaround time
  • Both inhibitor and substrate tests are provided
  • Available for a large panel of clinically-relevant DDI, ADME, Toxicity and therapeutic target transporters
  • Reliable and biologically relevant data from robust functional assays designed to meet stringent regulatory standards
  • All assay models overexpress recombinant transporters, providing clean and definitive results
  • Free technical consultation from experienced, customer-oriented scientists

The clinical response of a drug is driven by both on-target and off-target pharmacological effects. Because transporters are key determinants of drug ADME, toxicity, and drug-drug interactions (DDI), as well as being key therapeutic targets themselves, unexpected interactions with transporters can strongly influence the clinical pharmacology and therapeutic use of drugs. In vitro transporter profiling is a valuable tool for the early identification of undesirable drug-transporter interactions associated with serious clinical safety and DDI liabilities. In addition, transporter profiling can be applied to study the MOA of clinical drug responses, including off-target pharmacological effects and inter-individual variability in treatment efficacy, leading to the identification of new therapeutic indications for existing drugs and discovery of biomarkers to guide personalized medicine.

Please contact us to discuss your specific transporter profiling project.

Transporter Profiling Applications

Transporter proteins are key determinants of drug responses and toxicity. Many transporters are also emerging or validated as therapeutic targets for a variety of diseases, including depression, schizophrenia, cancer, and diabetes. Drug-transporter interactions, whether by serendipity or design, can strongly influence the pharmacological responses of drugs. When compounds are designed to act on a particular transporter target (e.g. SERT, DAT, NET, and SGLT2), specificity profiling of closely related transporters is necessary to ensure compound selectivity toward the primary target.

On the other hand, drugs oftentimes interact with transporters as an off-target effect. Such unexpected interactions can strongly influence the pharmacokinetic and pharmacodynamic attributes of drugs, leading to serious safety and DDI issues. Early-stage transporter profiling is therefore commonly used to understand undesirable clinical outcomes and/or guide follow-up clinical investigations. For instance, substrate and inhibition profiling of ddi transporters known to be involved in DDI is requested by the FDA, EMA and PMDA for New Molecular Entities (NCEs) in order to assess their potential DDI liabilities and to guide necessary clinical DDI studies. As another example, the pharmaceutical industry is increasingly conducting in vitro pharmacological profiling testing with the monoamine transporters SERT, DAT and NET, as well as the bile salt efflux transporter BSEP, to reduce safety-related drug failure.

Another powerful application of transporter profiling is to elucidate the molecular mechanisms that drive certain clinical outcomes. For example, the equilibrative nucleoside transporter ENT1 has been found to affect gemcitabine efficacy in treating pancreatic cancers because gemcitabine is transported by this transporter, resulting in ENT1 being proposed as a biomarker for selecting patients that are more likely to benefit from gemcitabine treatment. As another example, in vitro transporter profiling revealed that the anti-tumor drug oxaliplatin is transported by the organic cation transporter OCT2. Because OCT2 is highly expressed in peripheral neurons, this mechanism is proposed to be the cause of oxaliplatin induced peripheral neuropathy. This finding has led to the pursuit of specific OCT2 inhibitors to reduce oxaliplatin toxicity.

Considerations on Implementing Transporter Profiling Projects

A key requirement for transporter profiling projects is the availability of robust functional transporter assays. Optivia has developed the world’s largest portfolio of in vitro transporter assays. All of Optivia’s assays employ direct measurement of transporter functional activity, providing more biologically-relevant results in comparison with indirect binding assays. These robust, validated assays have been extensively used in regulatory-compliant transporter studies for clinical-stage compounds, as well as being suitable for early-stage mechanistic transporter profiling studies. Our robust assays and extensive experience enable rapid delivery of high-quality assay data for a variety of transporters, making it easier for you to discover selective transporter modulators and to identify particular transporters responsible for the pharmacological effects of your drugs.

Transporter Profiling Resources:

Reducing safety-related drug attrition: the use of in vitro pharmacological profiling

US FDA, Guidance for Industry Drug Interaction Studies —Study Design, Data Analysis, Implications for Dosing, and Labeling Recommendations (draft guidance), Feb. 2012

European Medicines Agency (EMA), Guideline on the investigation of drug interactions, June 2012

Membrane transporters in drug development

SLC transporters as therapeutic targets: emerging opportunities

Membrane transporters and drug response

Beyond the ITC White Paper: emerging sciences in drug transporters and opportunities for drug development

Uptake Carriers and Oncology Drug Safety

Human Equilibrative Nucleoside Transporter 1 Levels Predict Response to Gemcitabine in Patients With Pancreatic Cancer

Oxaliplatin-induced neurotoxicity is dependent on the organic cation transporter OCT2

Organic Cation Transporters Are Determinants of Oxaliplatin Cytotoxicity