tumor-infiltrating

(Z)-Leukadherin-1 (ADH-503 free base) is an allosteric agonist of CD11b.

ADH-503 (GB1275) is an orally available, allosteric CD11b small molecule agonist that can lead to repolarization of tumor-associated macrophages, reduction in the number of tumor-infiltrating immunosuppressive myeloid cells, and enhancement of dendritic cell responses.

AZ10397767 is a potent CXCR2 antagonist (IC50 = 1 nM). AZ10397767 significantly reduced the numbers of infiltrating neutrophils into both in vitro and in vivo tumor models.

AB-3PRGD2 is a radiolabeled agent that targets integrin αvβ3. It enhances tumor uptake and prolongs retention time in tumors, significantly improving the inhibition of tumor growth. AB-3PRGD2 also remodels the tumor immune microenvironment by upregulating PD-L1 expression and increasing tumor-infiltrating CD8+ T cells.

PI3Kδ-IN-25 is an orally active and selective PI3Kδ inhibitor with an IC50 of 2.1 nM. It exhibits IC50 values of 272, 285, and 1171 nM for PI3Kα, PI3Kγ, and PI3Kβ, respectively. In B16F10 cells, PI3Kδ-IN-25 inhibits the phosphorylation of AKTSer473, suppresses Treg cell proliferation, and downregulates the expression of PD-L1. In mouse models of B16F10 melanoma and Lewis lung cancer, PI3Kδ-IN-25 demonstrates anticancer activity by reducing tumor-infiltrating Treg cells and enhancing immune responses. This compound is applicable for research on cancers such as melanoma and lung cancer.

EVT0185 is an orally active ATP citrate lyase (ACLY) inhibitor. In the liver, it is converted by SLC27A2 into a CoA thioester, which interacts with the CoA binding site of ACLY. EVT0185-CoA inhibits ACLY activity with an IC50 of 2.5 μM. It mimics the immune and antitumor effects seen with ACLY gene deletion. Additionally, EVT0185 elevates levels of tumor-infiltrating B cells and the chemokine CXCL13. It is applicable in cancer research, including hepatocellular carcinoma (HCC).

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).

Tyrosinase (206-214), human (AFLPWHRLF), is a 9-amino acid peptide and an epitope of tyrosinase recognized by HLA-A24 restricted tumor-infiltrating lymphocytes (TIL) [1].

PD-L1-IN-2, a Naamidine J derivative, serves as a promising antineoplastic immunomodulator by hindering PD-L1 activity. In vivo studies indicate that it suppresses PD-L1 expression and amplifies tumor-infiltrating T-cell response, thus exerting anticancer effects. This compound is particularly utilized in the investigation of colorectal cancer [1].

SWS1, a d-(+)-biotin-conjugated PD-L1 inhibitor (IC50: 1.8 nM), displays anticancer activity by augmenting tumor-infiltrating lymphocytes and demonstrating anti-tumor efficacy, as evidenced by a 66.1% tumor growth inhibition (TGI=66.1%) in the B16-F10 mouse model [1].

MK-4166 is a humanized IgG1 agonistic monoclonal antibody targeting GITR. It is capable of enhancing the proliferation of both naive T lymphocytes and tumor-infiltrating T lymphocytes.