| Target | R&DImagingDOSIMETRYPH I/II |
|---|---|
| PSMA |
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PSMAPSMA is a transmembrane protein that is markedly overexpressed in approximately 90% of prostate malignancies, making it an excellent target for prostate cancer. In 2021, prostate cancer accounted for 13.1% of all new cancer cases and 5.6% of all cancer-related deaths. Current treatments have proven to be highly effective resulting in a five-year relative survival rate of nearly 100% in localized disease. Metastatic prostate cancer has a 5-year survival rate of less than 30%. As such, accurate initial staging of patients, early detection of recurrence, and response monitoring are critical to improving prostate cancer treatment. |
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| MC1R |
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MC1RMelanocortin 1 receptor (MC1R) is a cell surface endocytic receptor with seven transmembrane domains that belong to the G-protein-coupled receptor family. Abnormal expression of MC1R is associated with the development of skin cancer, and it has been reported that high expression of MC1R in melanoma promotes the progression of its development. Thus, MC1R is thought to be associated with a poor prognosis and a potential target for the treatment of melanoma. The survival curve also showed that high MC1R expression is associated with a shorter 5-year survival time and higher mortality in CRC |
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| SKP2 |
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SKP2S-phase kinase-associated protein 2 (SKP2), also known as p45 or FBXL1, is one of the members of the F-box protein family, which participates in ubiquitination, cell cycle control, and signal transduction in the form of the SKP2-SCF complex (Cul1-Rbx1-SKP1-F-boxSKP2). Over-expression of Skp2 is often associated with higher grades and a greater malignancy of tumors as well as a poor prognosis of cancers, such as breast cancer, nasopharyngeal carcinoma, rectal cancer treated with chemoradiotherapy, oral squamous cell carcinomas, and non-small-cell lung cancer, which suggests that Skp2 engages in tumorigenic activity and is a promising target for cancer therapy. There are several inhibitors designed and synthesized against SKP2 that are still under investigation in the pre-clinical phase such as SZL-P1-41 for Prostate and long tumor xenografts, Dioscin for Colorectal adenocarcinoma xenografts, FKA for Synovial sarcoma, osteosarcoma xenografts and prostate cancer in vivo models, SKPin C1 for Uveal melanoma xenografts. The only inhibitor i.e., in the Phase 1 trial is Betulinic acid with its anticancer activity against cutaneous metastatic melanoma. |
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| PP2A |
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PP2AProtein phosphatase 2A (PP2A) comprises a family of serine/threonine phosphatases and is involved in diverse regulatory functions, including cell cycle progression, apoptosis, and DNA repair. Although PP2A has historically been identified as a tumor suppressor, inhibition of PP2A has paradoxically demonstrated potential as a therapeutic target for various endometrial cancers. as well as in other gynecologic malignancies, such as ovarian and cervical cancer. DT-061/(AZD6244) is an orally bioavailable activator of PP2A for KRAS-driven lung cancer mouse models, lung adenocarcinoma xenografts, and non-small cell lung cancer xenograft, however haven’t got FDA approval yet. Compound FTY720 was synthesized for targeting PP2A against leukemia, colon cancer, non-small cell lung cancer, breast cancer, hepatocellular carcinoma, and prostate cancer, still under preclinical trials. OP449 has also been discovered for targeting PP2A against AML, breast cancer, and pancreatic cancer. Perphenazine was the other compound designed for PP2A against Brain, breast, colon, pancreatic, liver, skin, and lung cancer, ovarian and oral carcinoma, and leukemia and lymphoma cell lines T-ALL and melanoma xenografts. Interestingly LB-100 was the only compound in Phase I/II Clinical studies with the case numbers NCT03886662, NCT04560972, NCT03027388. |
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