PROTAC / molecular glue represents a novel class of therapeutic molecules that achieve targeted treatment through precise modulation of protein degradation or interactions. Leveraging the unique bifunctional design and mechanism of action of these molecules, InnoStar has systematically addressed research challenges and established a non-clinical evaluation system for PROTAC / molecular glue that meets regulatory standards. With the capability to support global multi-center submissions, InnoStar is dedicated to providing partners with efficient and reliable R&D services to accelerate innovative drug development. We has cumulatively served over a dozen related drug development projects, including pioneering initiatives such as China's first IRAK4 protein degrader, demonstrating "first-in-class" innovation both domestically and internationally.

InnoStar PROTAC / Molecular Glue Solutions

Early Screening Strategies for PROTAC / Molecular Glue Candidates

-Target protein binding affinity screening
-Preliminary in vitro degradation activity screening
-Cross-reactivity analysis of species-homologous proteins
-Serum protease stability testing
-Early in vivo target protein degradation validation (e.g., tissue sample analysis in murine models)

Non-Clinical Pharmacokinetics

-In vivo pharmacokinetics: Investigation of drug metabolism following single and repeated dosing, with high-sensitivity detection of plasma/tissue samples to analyze pharmacokinetic behavior of parent molecules and metabolites.
-In vitro metabolic stability: Conducting liver microsome/hepatocyte stability tests and metabolite identification to evaluate enzymatic pathways and stability in vitro.
-Drug interaction studies: Performing CYP inhibition/induction and transporter interaction studies to assess metabolic/excretion competition potential with other drugs.

Non-Clinical Safety Evaluation

-Safety pharmacology: Assessing effects on critical system functions (e.g., cardiovascular, respiratory, and central nervous systems).
-General toxicology: Evaluating long-term dosing toxicity in animals, with study design and analysis based on bifunctional molecular structure and E3 ligase distribution, alongside toxicokinetic investigations.
-Genetic toxicity testing: Assessing potential risks of genotoxic impurities and off-target degradation products based on molecular structure and synthesis processes.
-Reproductive toxicity testing: Evaluating reproductive toxicity, with attention to potential impacts from widespread E3 ligase expression.
-Carcinogenicity testing: Determining necessity based on mechanism of action and long-term exposure requirements, in alignment with relevant guidelines.
-Immunogenicity/immunotoxicity: Assessing risks of anti-drug antibody production and immune activation due to aberrant protein degradation.
-Off-target toxicity screening: Analyzing binding potential to non-target E3 ligases or proteins to evaluate tissue damage risks.
-Formulation safety: Examining chemical stability and dissolution properties in solution/solid formulations.

Clinical Bioanalysis

-Biomarker analysis: Evaluating relationships between drug exposure, target protein degradation, efficacy, and toxicity to optimize molecular design.
-Free molecule and metabolite analysis: Utilizing ultra-high-sensitivity LC-MS/MS for quantitative analysis of PROTAC / molecular glue in biological matrices.
-Target protein degradation monitoring: Employing ELISA, flow cytometry, and other platforms to assess degradation efficiency and dynamics in tissues/cells.
-Immunogenicity analysis: Using ELISA and cell-based assays to evaluate anti-drug antibody production and immune complex formation risks.
-Off-target binding surveillance: Screening non-specific binding potential to non-target proteins via proteomics technologies.

Project Experience

Cumulatively completed: Over a dozen new drug R&D projects, with 4 NMPA IND approvals, including successful China-U.S. dual IND submissions.

Partner with InnoStar for your PROTAC / molecular glue program and accelerate your path from discovery to approval with confidence.