Online Inquiry
p53 Inhibitor Development
p53 protein is a tumor-forming inhibitory transcription factor that affects cellular plasticity and is frequently lost in more aggressive prostate cancers with neuroendocrine differentiation. Therefore, the development of inhibitors targeting p53 is important for therapy of prostate cancer. At Alfa Cytology, our scientists have been dedicated to researching p53 inhibitors for many years and we offer a comprehensive one-stop p53 inhibitor development service for prostate cancer.
Introduction to p53 Inhibitor
p53 protein is an important tumor suppressor protein encoded by the TP53 gene, and in prostate cancer TP53 mutations are potential biomarkers that lead to or poor prognosis a set of insensitivity to multiple therapeutic regimens. Loss of p53 counteracts the effects of AR inhibitors and increases the proliferation rate of prostate cancer cells. Considering the important role of p53 inactivation in cancer development, restoration of wild-type p53 function by p53 reactivation compounds developed with different approaches seems to be an attractive therapeutic strategy for prostate cancer.
Fig.
1 Therapeutic potential of p53 reactivation in prostate cancer: Strategies and opportunities. (Kumari, S., et
al. 2022)
Structure of p53 Protein
As with most cancer therapies, drug resistance develops over time. Therefore, further understanding of potential combination therapies that explore CDK4/6 to slow or overcome drug resistance is critical.
Transactivation Domain (TAD)
TAD is located at the N-terminus of the p53 protein and consists of two sub-structural domains, TAD1 and TAD2. This region is critical for the transcriptional activity of p53, providing binding sites to the transcription machinery and the negative regulator MDM2, which targets p53 for proteasomal degradation.
DNA Binding Domain (DBD)
DBD is responsible for binding and recognizing sequence-specific DNA, which is the core of the biological function of p53 as a transcription factor. It contains four of the five conserved regions of p53 and is capable of interacting with different proteins to coordinate and subtly regulate various biological functions.
Tetramerization Domain (TD)
TD is located near the C-terminus of the p53 protein and consists of residues 324-356. This structural domain is required for p53 tetramerization, through which the p53 protein can reversibly form a tetramer. Tetramer formation is essential for the p53 protein to effectively bind DNA and regulate downstream gene expression.
p53 Inhibitor Development for Prostate Cancer
| Name | Target | Phase | Company | Country |
| APR-246 | p53 | Phase I/IIa | Aprea Therapeutics | USA |
Our Services
As a highly recognized pioneer in the global inhibitors field, we have professional knowledge and extensive experience. At Alfa Cytology, we strive to develop safer, more effective, and more personalized therapies by constantly advancing the research and development of p53 inhibitors development.
Workflow for p53 Inhibitor Development
Target Identification and Validation
Utilizing advanced techniques to identify and validate p53 targets implicated in prostate cancer.
Lead Compound Identification
Lead Compound Identification Employing high-throughput screening and computational modeling to identify lead compounds with high potency and selectivity.
Preclinical Efficacy Testing
Conducting rigorous in vitro and in vivo studies to assess the efficacy and safety profile of lead compounds.
Medicinal Chemistry Optimization
Iteratively optimizing lead compounds for improved pharmacokinetic and pharmacodynamic properties.
One-stop Solutions for p53 Inhibitor Development
Alfa Cytology aims to provide customized one-stop p53 inhibitors development services in the field of prostate cancer therapy. If you are interested in our services, please don't hesitate to contact us for further information and pricing details.
Reference
- Kumari, S., et al. Therapeutic potential of p53 reactivation in prostate cancer: Strategies and opportunities. European journal of pharmacology. 2022, 919: 174807.
For research use only.