Cuproptosis, a recently identified copper-dependent programmed cell death pathway, has emerged as a promising strategy in cancer therapy. Its effectiveness is closely linked to intracellular copper accumulation but is mitigated by elevated levels of glutathione (GSH) in tumor cells. A significant barrier to its clinical application lies in the challenge of facilitating the cellular uptake of copper ions. Additionally, intracellular copper ions rapidly bind with GSH, further complicating the induction of tumor cell death. Notably, no existing ionophore drug simultaneously acts as both a copper ionophore and a GSH scavenger to effectively induce cuproptosis.
Antibody-drug conjugates (ADCs) represent a cutting-edge class of targeted cancer ther- apeutics, seamlessly integrating the high specificity of monoclonal antibodies with the cytotoxic power of chemotherapy agents. This strategic union facilitates the precise de- livery of a potent cytotoxic payload to HER2-expressing cancer cells, where HER2 is a well-established therapeutic target. Despite the promising efficacy of HER2-directed ADCs in treating HER2-positive breast cancer, the emergence of resistance in tumor cells poses a significant obstacle to their therapeutic potential.
Antibody drug conjugates (ADCs) are a class of rapidly developing targeted biotherapeu- tic drugs, which consist of three elements: antibody, linker, and payload. ADCs combine the high specificity of antibodies with the potency of payloads, delivering the highly effi- cient small molecule within the target tumor cells.
As one of the new payload types, stimulator of interferon genes (STING) agonist can initi- ate the innate immune response, enhancing the attack on tumor cells. STING agonist ADCs, allowing tumor-localized activation of STING, may achieve greater anti-tumor ac- tivity and better tolerability.
By combining the STING binding assay, different THP-1 reporter assay, and cytokine re- lease detection, ICE Bioscience can support for STING agonist activities screening. West- ern blotting assay can be applied for demonstrating the molecular mechanisms of candi- dates. For specific screening and evaluation of HER2 STING agonist ADCs, cell binding assay, cell internalization assay, HER2 overexpression reporter assays, co-culture assays of tumor cell lines or STING knockout tumor cell lines with THP-1, hPBMC, as well as whole blood can be utilized at different project stages.
Molecular glue degraders (MGDs) induce the proximity of target proteins to E3 ubiquitin ligases, leading to target protein ubiquitination and subsequent degradation by the proteasome. Unlike conventional inhibitors that target enzymatic activity, these molecules enable the degradation of proteins previously deemed "undruggable," thereby rendering them "druggable". With a first-in-class VAV1-directed MGDs (MRT6160) enters in clinical phase I, VAV1 degraders showed the remarkable potential in Immunology and inflammatory diseases such as rheumatoid arthritis and colitis. Current advancements highlight its ability to reduce proinflammatory cytokine production, inhibit pathogenic T cell polarization, and mitigate autoimmune responses.
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