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WNT Inhibitor Development
Malignant transformation of prostate cells, development of primary prostate cancer and its progression to castration-resistant prostate cancer (CRPC) are affected by direct and indirect interactions of the WNT signaling pathway. Therefore, inhibitors targeting the WNT signaling pathway have potential in preventing prostate cancer progression. At Alfa Cytology, we provide a comprehensive one-stop service for the development of WNT inhibitor for prostate cancer.
Introduction to WNT Inhibitor
The prostate is a multistage progressive disease with a complex pathogenesis that is thought to result from a combination of genetic and environmental factors.The WNT signaling pathway directly and indirectly influences the malignant transformation of prostate cells, the development of primary prostate cancer, and its progression to castration-resistant prostate cancer (CRPC).
Fig.
1 The canonical WNT signaling pathway in prostate carcinogenesis and potential WNT-based treatments. (Hou, Y.,
et al. 2024)
The WNT signaling pathway is a key cascade that regulates embryonic development and tissue homeostasis by controlling cell proliferation, differentiation, and apoptosis.The WNT signaling pathway is divided into the canonical WNT signaling pathway (WNT/β-catenin signaling pathway) and the non-canonical WNT signaling pathway, which mainly consists of the WNT/PCP signaling pathway and the WNT/Ca2+ signaling pathway.
WNT Inhibitor Development for Prostate Cancer
| Name | Target | Type |
| Porcupine | LGK974 | Small molecule inhibitor |
| ICG001 | β-catenin: CBP | Small molecule inhibitor |
| iCRT3 | β-catenin: TCF4 | Small molecule inhibitor |
| DKN-01 | DKK1 | Monoclonal antibody |
| Vantictumab (OMP-18R5) | FZD1/2/5/7/8 | Monoclonal antibody |
| IgG-2921 | FZD5 | Monoclonal antibody |
| Septuximab vedotin (F7-ADC) | FZD7 | Antibody drug conjugate |
Our Services
Aberrant WNT signaling has been implicated in prostate cancer tumorigenesis and metastasis in preclinical models, suggestting that WNT-targeted therapy is critical for prostate cancer. Alfa Cytology has been deeply involved in the field of prostate cancer therapy development, and we have professional knowledge, extensive experience, and cutting-edge technology to escort you through the process of WNT inhibitors development.
Offering complete development of small molecule inhibitors, from discovering lead compounds to enhancing their chemistry, screening, and adjusting them for better performance.
Providing all-in-one services for creating monoclonal antibodies, involving selecting B-cells, using hybridoma tech, purifying antibodies, and making further engineering tweaks.
Developing ADCs means linking a toxic drug to a monoclonal antibody with a chemical linker for precise delivery, targeting tumor cells strongly while minimizing harm to healthy ones.
Mouse Models for WNT Signaling in Prostate Cancer
In order to develop effective therapy based on genetic changes, a series of genetically engineered mouse models (GEMMs)have been developed to study the functional consequences of dysregulated WNT pathway components in prostate cancer.
| Model | Prostate Phenotype |
| PBCre4 Apcfl/fl | Hyperplasia (4.5 weeks) and adenocarcinoma (7+ months) with keratinized squamous metaplasia. Castration-resistant. |
| Nkx3.1Cre β-catfl/fl | Neonatal lethal. Ex vivo E18.5 prostate cultures display impaired budding and branching upon β-catenin deletion. |
| Nkx3.1-CreERT Apcfl/flSmad4fl/fl | Co-deletion of Apc and Smad4 causes invasive prostate cancer progression not observed in single mutants. |
| PBCre4 β-catfl/fl | Normal adult prostate tissue, despite B-catenin deletion. |
| PBCre4 β-catfl/fl Ptenfl/fl | Pten-deficient prostate tumor growth unaffected by β-catenin loss (±castration). |
| PBCre4 Hi-Myc δ-cat-/- | δ-catenin loss of function accelerates Hi-Myc-driven prostate cancer progression. |
| MPtApc (EPO-GEMM) | Metastatic AR-negative, NE-negative prostate cancer (median survival: 47 days). |
| WNT5a-/+ TRAMP ART877A | WNT5a depletion reduced NEPC formation and progression. |
| Col1a2-CreERT2 β-catfl/fl | β-catenin loss in stromal cells increases prostate weight and prostate epithelial cell proliferation. |
Workflow for WNT Inhibitor Development
Alfa Cytology aims to provide customized one-stop WNT 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
- Hou, Y., et al. Combination therapies with WNT signaling inhibition: A better choice for prostate cancer treatment. Biochimica et biophysica acta. Reviews on cancer. 2024, 1879(1): 189186.
For research use only.