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AR Signaling Axis Inhibitor Development
Androgens play an important role in the growth of normal prostate and prostate tumors, targeting androgen signaling has been an important tool for treating aggressive prostate cancer. Alfa Cytology has extensive experience in therapies development targeted to AR signaling axis in prostate cancer, and aims to provide one-stop development services for biotech and biopharmaceutical companies worldwide.
Introduction to AR Signaling Axis
Prostate cancer (PCa) is a deadly malignancy that is now one of the leading causes of cancer-related deaths among men in the United States. Androgens play an important role in the growth of prostate and prostate tumors. Therefore, targeting androgen signaling has remained an important therapy option of metastatic prostate cancer for the past several decades.
Fig. 1 AR
signaling pathway and targeted therapeutic approaches in PCa. (He, Y., et al. 2022)
Structure of Androgen Receptor
The gene encoding AR is located on chromosome Xq11.2-q12 and consists of eight exons spanning 186,587 kb. The structure of AR has high structural similarity to other steroid receptors such as progesterone receptor (PR), estrogen receptor (ER), glucocorticoid receptor (GR) and thyroid hormone receptor (THR). And the structure of AR consists of several functional domains, including the the ligand binding domain (LBD), the DNA binding domain (DBD), N-terminal transcriptional regulatory domain (NTD), and the hinge region.
LBD is responsible for binding to androgens such as testosterone. When
androgens bind to the LBD, the AR undergoes a conformational change that activates its transcriptional
activity.
DBD contains two zinc finger structures that are responsible for
recognizing and binding to specific sequences on DNA.The DBD ensures that the AR can be precisely
localized to target genes in the genome.
NTD occupies more than half of the AR protein. NTD contains activation
factor 1 (AF1), which is the main effector region of the AR and is essential for the transcriptional
activity of the AR.
The hinge region is located between the LBD and DBD, which allows these
two structural domains to be spatially separated and correctly oriented so that the AR can bind
efficiently to DNA and androgens.
Therapy Development Targeted to AR Signaling Axis in Prostate Cancer
| Name | Phase | Company | Country |
| H001 | IND-enabling | Halda Therapeutics | USA |
| Proxalutamide | Phase I | Kintor Pharmaceutical Limited | China |
| X-Synergy | Phase I | Kanpu Biopharma | China |
| TAS-3681 | Phase I | Taiho Pharmaceutical | Japan |
| KZR-261 | Phase I/II | TRACON Pharmaceuticals | USA |
| TRC253 | Phase I/IIA | TRACON Pharmaceuticals | USA |
| Darolutamide | Market Approval | Bayer AG & Orion Corporation | Germany & Finland |
Our Services
Currently, small molecule drugs such as inhibitors targeting the AR signaling pathway are the main drugs being developed for therapy of prostate cancer. At Alfa Cytology, we are committed to providing comprehensive preclinical services that support the therapies development targeted to AR signaling axis in prostate cancer, including AR signaling inhibitor and GnRH sntagonists/sgonists.
TARGET ID
AND VALIDATION
HIT ID AND OPTIMIZATION
LEAD
OPTIMIZATION CANDIDATE SELECTION CANDIDATE PROFILING
OPTIMIZATION CANDIDATE SELECTION CANDIDATE PROFILING
- Genetics
- Molecular biology
- Cell-based studies
- Animals studies
- Screening
- Hit pharmacology profiling
- Medicinal chemistry
- In vitro ADME
- Physiochemical properties
- Medicinal chemistry
- Pharmacology
- In vitro and in vivo ADME
- Physiochemical properties
- Initial animals efficacy studies
- Higher species PK
- Animals efficacy
- Preliminary rodent toxicology
- Preliminary toxicology
- Version and form screening
- Formulation development
- Version and form selection
- Formulation development
- Rodent and higher species toxicology
- Definitive
- IND preparation
One-stop Solutions for Development Targeted to AR Signaling Axis
Alfa Cytology offers a full range of services for therapies development targeted to AR signaling axis in prostate cancer, including but not limited to the following.
Our Advantages
Our company is committed to providing customized one-stop services to accelerate your project development. With professional knowledge, we are committed to providing you with reliable experimental solutions, efficiently providing you with round-the-clock development services to ensure that your development is of low cost and confidentiality.
Qualified Experiment
Timely Delivery
Cost-Effective Services
Highly Confidential
Alfa Cytology aims to provide customized one-stop development services to support your innovations and breakthroughs in the field of prostate cancer therapy in order to accelerate the development and commercialization of new therapies. If you are interested in our services, please don't hesitate to contact us for further information and pricing details.
Reference
- He, Y., et al. Targeting signaling pathways in prostate cancer: mechanisms and clinical trials. Signal transduction and targeted therapy. 2022, 7(1): 198.
For research use only.