- Clinical Pipeline
- Guadecitabine (SGI-110) DNMT inhibitor (Hematological Malignancies and Solid Tumors)
- ASTX029 Extracellular Signal-Related Protein Kinases (ERK 1/2) Inhibitor (Solid Tumors)
- ASTX727 Oral DNMT inhibitor (Hematological Malignancies)
- ASTX660 Dual IAP Antagonist (Solid Tumors & Lymphomas)
- ASTX295 Oral Murine Double Minute 2 (MDM2) antagonist (Solid Tumors)
- Partnered Products and Programs
- Kisqali®(ribociclib) CDK4/6 inhibitor (Oncology)
- Balversa® (erdafitinib) FGFr inhibitor (Oncology)
- AZD5363 PKB/Akt Inhibitor (Oncology)
- Multiple Targets and Therapeutic Areas
- Pyramid™ Discovery Platform
- Oncology and CNS Discovery
- Sustaining Innovation
Integrated Platform, Innovative Solutions
Astex is recognized as a pioneer and global leader in fragment-based drug discovery, a new way of generating novel small molecule drugs, and one of the most significant advances in drug discovery in the past 20 years.
We employ Pyramid™, our proprietary fragment-based drug discovery platform, to rapidly deliver customized, high-quality drug leads with enhanced therapeutic potential across a wide variety of therapeutic targets and disease areas, including those regarded as “intractable” by the pharmaceutical industry.
Advantages of fragment-based drug discovery
- Designed to reduce attrition during drug development
- Carefully monitors key characteristics such as ligand efficiency and in vivo activity during lead optimization
- Ensures delivery of potent, selective and low molecular weight compounds with optimized drug metabolism and pharmacokinetic properties
- Generates higher quality leads by optimizing key drug properties earlier in the process
How fragment-based drug discovery works
Conventional drug discovery and development, which relies heavily on high-throughput screening (HTS), has not delivered on its promise of increasing the numbers and quality of new drugs entering clinical trials. This is in part due to the complexity and the relatively large size of the compounds routinely being screened as well as the challenge of optimizing the hits derived from this approach.
Fragment-based drug discovery:
- Starts with very small, low molecular weight drug fragments
- These fragments have the potential to keep the overall complexity and molecular weight of each drug candidate low
- These are key factors in successful drug development
Pyramid™ screening and rational drug design
Traditional bioassays used in HTS are generally unable to detect such small drug fragments because of their low potency binding to the protein target.
The Pyramid™ platform integrates a range of high-throughput biophysical techniques for screening such as X-ray crystallography, nuclear magnetic resonance spectroscopy, and calorimetry with fragment library design and computational methodologies. These are used to experimentally characterize in detail the interactions of very low molecular weight compounds (fragments) with their target proteins.
Unlike conventional screening techniques, the Pyramid™ process enables precise details of fragment binding to be routinely identified and visualized therefore allowing for rational molecule design.
Astex is a member of the Cambridge Pharmaceutical Cryo-EM Research Consortium to assist early-stage drug discovery research. Astex is developing Cryo-electron microscopy (Cryo-EM) technology as a further biophysical technique to be used in FBDD.
- Affords a detailed understanding of the fragment’s binding environment at an atomic level
- These structural insights support a very efficient chemistry optimization process in which each additional functional group is designed to contribute to protein binding in a defined and productive manner
- Drug candidates are designed to have lower molecular weight, reduced metabolic liability, improved target selectivity and ease of chemical synthesis