c-mesenchymal-epithelial transforming factor (c-MET), also known as hepatocyte growth factor receptor, is the only known receptor with high affinity for its natural ligand hepatocyte growth factor (HGF). c-MET is a well-characterized oncogene that is the target of many drugs including small molecules, biologic pathway inhibitors, and antibody-drug conjugates (ADCs). Currently, BOC Sciences provides comprehensive ADC construction services for c-MET targets. We specialize in the design and development of targeted drugs for cancer diseases and offer a broad range of ADC development services.
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c-MET is a receptor tyrosine kinase with a high-affinity ligand, hepatocyte growth factor/scatter factor (HGF/SF). In tumor cells, inactivation of c-MET may affect important cell growth processes such as cell growth, differentiation, apoptosis and invasion. The regulation of cancer cell life cycle by c-MET confers the possibility of c-MET as a potential target in cancer. The regulatory role of c-MET in gastric cancer, head & neck cancer, breast cancer, kidney cancer and lung cancer has been reported in the literature. ADC is an immunotherapy that directs its loaded cytotoxic small-molecule drugs to specific tumor sites through the targeting of antibodies. Currently, c-MET-based ADCs are being extensively studied to enhance the chemotherapeutic efficacy of targeted agents and reduce systemic exposure and toxicity.
Fig. 1. Diagram showing important functional domains of c-MET (Cancer-Leading Proteases. 2020, 295-326).
SHR-A1403 is a novel ADC pipeline targeting the c-MET receptor. Structurally, SHR-A1403 is conjugated to an anti-c-MET monoclonal antibody and SHR152852 small molecule cytotoxin via a non-cleavable thioether linker. Preclinical pharmacokinetic studies indicate that SHR-A1403 has high affinity for human c-MET. In addition, SHR-A1403 showed excellent antitumor activity in both tumor cells and xenograft models with high c-MET expression. Based on the above findings, the researchers speculate that the antitumor activity of SHR-A1403 mainly comes from the internalization and translocation of cytotoxins, resulting in the release of toxin molecules in lysosomes.
c-MET is majorly expressed in epithelial cells of liver, gastrointestinal tract, thyroid, kidney, stomach lining, brain, bone marrow, muscle, and the small and the large intestine besides been found in the basal keratinocytes of esophagus and skin during embryogenesis and adulthood. Researchers have found that c-MET in oncogenic transformation and wide spread spectrum of tumor malignancies. It plays a key role in metastasis and poop prognosis of cancer, suggesting that inhibition of c-MET signaling may help in abrogating cancer growth and enhancing therapeutic efficacy. Our c-MET targeted ADC development services including:
|Breast Cancer||Breast cancer is the most common cancer in women and the main cause of cancer-related deaths global. Studies have shown that c-MET is overexpressed in approximately 20%-30% of breast cancer patients and approximately 52% of triple-negative breast cancer patients, making c-MET a promising target for breast cancer therapy.|
|Pancreatic Cancer||c-MET is a marker of normal pancreatic stem and progenitor cells. However, increased transcription in pancreatic cancer leads to overexpression of the c-MET receptor, which will increase c-MET promotes tumor growth and reproduction through multiple mechanisms.|
|Hepatocellular Carcinoma (HCC)||Aberrant c-MET activity is associated with the development of HCC, suggesting the therapeutic potential of c-MET inhibitors. Studies have shown that c-MET abnormalities occur in approximately 50% of HCC patients and may arise through gene mutation, gene amplification, increased mRNA expression, and receptor overexpression.|
|Epithelial Ovarian Cancer (EOC)||EOC is one of the leading causes of cancer-related deaths in women, and the most lethal gynecologic malignancy. In EOC, c-MET overexpression was found to be approximately 7% to 27% and was associated with ovarian cancer progression and adverse outcomes.|
c-MET protein expression is also associated with poor prognosis in many solid tumors. So far, several clinically available tyrosine kinase inhibitors have shown efficacy in a subset of patients with tumors exhibiting c-MET gene amplification (e.g., 6% of gastric cancers and 1% of lung cancers) or exon 14-skipping mutations. BOC Sciences is the undisputed global leader in providing custom ADC design and development services for a variety of diseases. We now provide high-quality ADC preparation services for cancers involving c-MET targets to help customers win in the ADC drug development pipeline.
Scientists from BOC Sciences provide a full suite of development services for client's research targets or oncology indications. Our services cover antibody modification, bioconjugation, small molecule synthesis, cGMP manufacturing and multiple analytical characterization support services.