SX-682

Agent Description

SX-682 is an oral allosteric small-molecule that inhibits CXCR1 and CXCR2 (CXCR1/2). Inhibiting both human isoforms is believed essential. CXCR1/2 are a combined "master switch" of the tumor microenvironment, where they control tumor cell metastasis, the epithelial to mesenchymal transition, the influx of immunosuppressive MDSCs and neutrophils and angiogenesis. Many human carcinomas, including breast, colon, cervical, gastric, lung, ovarian, and chordoma, among others, express high levels of CXCR1/2 ligands relative to normal tissues. Additionally, multiple clinical studies in melanoma, breast, ovarian, prostate and colon cancer have shown a direct correlation between serum levels of CXCR1/2 ligands and disease progression. SX-682 has been extensively validated in numerous preclinical tumor models, where it exhibits mono-agent anti-tumor activity, blocks metastasis, activates tumor killing by effector cells, reverses chemo-resistance, and potently synergizes with anti-CTLA-4 and anti-PD1.

Mechanism of Action

Allosteric inhibitor of CXCR1 and CXCR2

Classification

CXCR1 and CXCR2 inhibitor

Molecular Targets

CXCR1 and CXCR2 expressing cells

Monograph

SX-682 has been extensively validated in numerous preclinical tumor models, where it exhibits mono-agent anti-tumor activity, blocks metastasis, activates tumor killing by effector cells, reverses resistance to chemotherapy (e.g., carboplatin), and potently synergizes with anti-CTLA-4 and anti-PD1. Its activity in castrate-resistant metastatic prostate cancer was reported (Nature. 2017 Mar 30;543(7647):728-732). SX-682 is being studied in combination with pembrolizumab in newly diagnosed melanoma (NCT03161431).

Studies of Interest

SX-682 is expected to be broadly active across solid and hematologic cancers when combined with chemotherapy or immuno-therapy (e.g. checkpoint inhibitors, CAR-T, vaccines, and other inhibitors of the microenvironment). Studies of interest include proof-of-concept open-label phase 1 trials applying SX-682 in combination therapy or monotherapy. Investigators are encouraged to contact the Collaborator in advance of a formal LOI.

Information collaborator would like included in investigator proposals

N/A