mdscs

SX-682 is an orally available allosteric inhibitor of CXCR1 and CXCR2 that blocks tumor myeloid suppressor cell recruitment and enhances T cell activation and anti-tumor immunity, with the potential to treat castration-resistant prostate cancer.

Baccatin III (Baccatin Ⅲ) is a polycyclic diterpene which can be used for the semi-synthesis of paclitaxel and analogs. It has immunomodulatory and anticancer chemotherapeutic activities.

CXCR2 antagonist 3 (compound 11h) is a highly effective inhibitor of CXC chemokine receptor 2 (CXCR2), displaying double-digit nanomolar potencies in inhibiting neutrophil infiltration into the air pouch. Additionally, it reduces neutrophil and MDSC infiltration while enhancing CD3+ T lymphocyte infiltration into Pan02 tumor tissues [1].

CB-1158-analog, also known as Numidargistat-analog and INCB01158-analog, is a potent and orally active arginase inhibitor with IC50=89 nM) . CB-1158 blocked myeloid cell-mediated suppression of T cell proliferation in vitro and reduced tumor growth in multiple mouse models of cancer, as a single agent and in combination with checkpoint blockade, adoptive T cell therapy, adoptive NK cell therapy, and the chemotherapy agent gemcitabine. CB-1158 increased tumor-infiltrating CD8+ T cells and NK cells, inflammatory cytokines, and expression of interferon-inducible genes. CB-1158 may be potentially useful in renal cell cancer, breast cancer, non-small cell lung cancer, acute myeloid leukemia, and other tumor types where arginase-secreting MDSCs are known to play an immunosuppressive role. (see ADDITIONAL INFORMATION in this web page for CB-1158 structure confusion).

CSF1R-IN-22 (Compound C19), a potent orally administered CSF-1R selective inhibitor (IC50 <6 nM), significantly enhances CXCL9 secretion from M2 macrophages and promotes CD8+ T cell infiltration. Moreover, it amplifies the anti-tumor immune responses in conjunction with anti-PD-1 and triggers apoptosis in tumor cells. Additionally, CSF1R-IN-22 effectively reprograms M2-like TAMs (tumor-associated macrophages) to an M1 phenotype, modulates the tumor microenvironment (TME) by fostering the recruitment of CD8+ T cells, and diminishes the presence of immunosuppressive Tregs and MDSCs [1].