As a recognized leader in the field of drug discovery and development, coupled with more than a decade of experience, BOC Sciences is committed to the development of Protac®, we provide our customers with a comprehensive range of high-quality small molecule solubility and chemical stability services.
Chimera-targeted protein degradant (Protac®) is a new therapy. Compared with macromolecular drugs such as antibodies or oligonucleotides, it retains its ability to directly act on intracellular or cell membrane target proteins. At the same time, it also has the advantages of high oral bioavailability and low manufacturing cost of small molecular drugs. But a formidable challenge to prevent Protac® from realizing its therapeutic potential is its lack of pharmacological characteristics associated with oral drugs, that is, the "five rules" (Ro5) of Lipinski. The oral dose of the drug needs to have the characteristics of allowing dissolution and stability in the stomach, as well as from intestinal absorption and stability to the first metabolism to reach systemic circulation. Therefore, water solubility and stability are the two main physical and chemical properties that need to be optimized in the development of Protac® drugs.
- Solubility Prediction
A successful drug discovery strategy seems to be an attempt to optimize the balance between "hydrophobic-driven efficacy and hydrophilic-driven biopharmaceutical properties". Over-reliance on optimization efficacy and damage to physical and chemical properties will produce suboptimal ADMET (absorption, distribution, metabolism, excretion and toxicity) properties and reduce the likelihood of clinical success. Therefore, the calculation method that can qualitatively predict the physical and chemical properties (such as solubility) of the compound is the basic requirement of drug development before synthesizing the compound according to the molecular structure.
- Solubility Measurement
BOC Sciences provides efficient and repeatable methods for the determination of water solubility of small molecules, including the use of HPLC-UV, liquid chromatography-tandem mass spectrometry (LC-MS) analysis and solution calorimetry to determine the solubility and concentration of small molecules in shaking flasks. Which analysis method to choose depends on the nature and application of the Protac® candidate method.
- Improvement of solubility and stability
Physical modification includes particle size reduction such as micronization and nano-suspension, modification of crystal habits such as polycrystalline, amorphous and eutectic. Chemical modification including change of pH value, use of bufier, derivatization, complexation and salt formation, and other methods. Other technologies include supercritical fluid process, surfactant, Solubilizer, cosolvent, hydrophilicity and the use of new excipients. In addition, we have established an advanced high-throughput screening (HTS) platform to help our customers determine the best excipients to improve the solubility and stability of Protac® with low cost and shorter time.
- One-stop Protac® service platform
- Experienced scientific team
- Advanced instruments and equipment
- Analytical HPLC and MS analyses
- Senior scientists and advanced platform
- Data analysis, detailed report with results and discussion
- Churcher, I. (2018). Protac®-induced protein degradation in drug discovery: breaking the rules or just making new ones?. Journal of medicinal chemistry, 61(2), 444-452.
- Paiva, S. L., & Crews, C. M. (2019). Targeted protein degradation: elements of Protac® design. Current opinion in chemical biology, 50, 111-119.
* PROTAC® is a registered trademark of Arvinas Operations, Inc., and is used under license.