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Androgen Receptor Antagonists Library

The androgen receptor (AR) belongs to the nuclear receptor superfamily and contains 918 amino acid residues, which make up three important structural domains, namely the DNA bindingdomain (DBD), the ligand binding domain (LBD) and the nitrogen terminal binding domain (NTD). AR is a ligand-dependent transcription factor that regulates the expression of a range of downstream target genes upon androgen binding. Androgen receptor antagonists have been proved as promising targets for the treatment of prostate cancer. AR antagonists can be classified into steroidal AR antagonists and nonsteroidal AR antagonists based on their chemical structure.

BOC Sciences has designed its proprietary library of androgen receptor antagonists to provide structurally diverse androgen receptor antagonists, helping to find new scaffolds and sites for the treatment of prostate cancer.

Summary of androgen receptor response to AR agonists and AR antagonists in TNBC and prostate cancer cell lines. Figure 1. Summary of androgen receptor response to AR agonists and AR antagonists in TNBC and prostate cancer cell lines. (Thakkar, A.; et al. 2016)

Library Design

  1. Firstly, we apply a series of reliable reference of androgen receptor modulators
  2. Then, we perform an androgen receptor pharmacophore modeling:
    • Selected examples of know antagonists: Dihydrotestosterone (DHT), Enzalutamide, ODM-201, (R)-Blcalutamide, Phizer and Taiho patent
    • Key structural features of the known non-steroidal antagonists
    • NO2 is the commonly used restrictions and CN is preferable
    • HBD distance is variable in a wide range and OH is preferable
  3. Core selection
    • At least 3 functional groups, one functional group should be able to serve as an attachment point for warhead
    • Contain or be able to provide HBD group with variable in wide range distance CN-HBD groups within cores selection
    • Diverse 3D-orientations of exit vectors within cores selection
    • Lead-like properties (Ro3 for root core structure)
    • Sp3-Enriched, preferably with at least one chiral center
    • Synthetic feasibility
    • Ability to provide IP-clean field

Schematic view of the therapeutic medicines targeting androgen receptor signaling pathways. Figure 2. Schematic view of the therapeutic medicines targeting androgen receptor signaling pathways. (Obinata, D.; et al. 2014)

Androgen Receptor Antagonists Library Characteristics

Table1. Prameters for root compound

ParameterValue
MW144.17
logP-2.34
PSA75.35
Number of H Donors4
Number of H Acceptors4
Chiral centers2
Sp30-80
FRB3
Rule of Five0
  • All PAIN and reactive compounds are excluded from selection by internal filter applications
  • IC50, Ki, etc less than 10 μM, inhibition >25%
  • Confirmed bioactivity and safety via preclinical studies and clinical trials
  • All of the compounds have been selected by ligand efficacy and predicted binding mode
  • Structural diversity, significant efficacy, and cellular penetration
  • Structural document, IC50, and other chemical and biological data are provided
  • Tanimoto index ≥ 0.75
  • All compounds are continually updated
  • Compound cherry-picking service is provided

What We Deliver

  • Delivered within 2 weeks in any customer-preferred format
  • Powders, dry films or DMSO solutions formatted in vials, 96 or 384-well plates
  • All compounds have a minimum purity of 90% assessed by 1H NMR and HPLC
  • Analytical data is provided

BOC Sciences provides professional, rapid and high-quality services of Androgen Receptor Antagonists Library design at competitive prices for global customers. Personalized and customized services of Androgen Receptor Antagonists Library design can satisfy any innovative scientific study demands. Our clients have direct access to our staff and prompt feedback to their inquiries. If you are interested in our services, please contact us immediately!

References

  1. Thakkar, A.; et al. Vitamin D and androgen receptor-targeted therapy for triple-negative breast cancer. Breast Cancer Research & Treatment. 2016. 157(1): 77-90.
  2. Obinata, D.; et al. Review of novel therapeutic medicines targeting androgen signaling in castration-resistant prostate cancer. World Journal of Clinical Urology. 2014. 3(3): 264-271.
Our mission is to provide clients with a professional chemical library design platform. Empowered by high-quality services and effective research solutions, we are committed to helping customers achieve effective and successful research goals.

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Services Based on the Chemical Library Design Platform

Services Based on the Chemical Library Design Platform

BOC Sciences has rich experience in working with global customers in custom library synthesis of compounds and generating small to medium-sized libraries of target compounds. Our knowledge in generating a large number of target molecules in a remarkably shorter time enables quick biological screenings for affinities. With the target properties in mind, we deliver target molecules, by applying our extensive knowledge in drug discovery.

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