CB-1158 (INCB01158)
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| Catalog No. | APIM050027 |
|---|---|
| Product Name | CB-1158 (INCB01158) |
Description
Background Information:
CB-1158 (INCB01158) is an orally bioavailable, potent (IC50 = 98 nM), and selective (minimal off-target activity at 50000 nM) inhibitor of human arginase I, an immune-mediated anti-tumor agent. L-arginine is a critical metabolite for T-cell receptor signaling and subsequent T-cell proliferation, and depletion of arginine arrests T-cell growth. In the tumor microenvironment, infiltrating myeloid-derived suppressor cells (MDSCs), macrophages, and neutrophils produce arginase, which depletes local arginine concentrations and dampens T cell-mediated immune surveillance. Pharmacological inhibition of arginase is expected to restore arginine levels and allow T-cells to proliferate, thereby leading to an immune-mediated anti-tumor response. In culture, human granulocytes release arginase and deplete media arginine to levels that inhibit T-cell proliferation. In a co-culture system of human granulocytes and T-cells, CB-1158 potently blocks granulocyte-derived arginase activity, maintains extracellular arginine levels, and restores proliferation of T-cells (ref. 1). CB-1158 has single agent efficacy in mouse tumor models and synergistically enhances the antitumor efficacy of checkpoint inhibitors (ref. 2).
Reference:
1. M Works, et al, Abstract 552: Immuno-oncology agent CB-1158 is a potent and selective arginase inhibitor and causes an immune-mediated anti-tumor response, AACR; Cancer Res 2016; 76(14 Suppl): Abstract No 552.
2. K. P. Papadopoulos, et al, A first-in-Human Phase 1 Study of CB-1158, a Small Molecule Inhibitor of Arginase, as Monotherapy and in Combination with an Anti-PD-1 Checkpoint Inhibitor in Patients (pts) with Solid Tumors, J Clin Oncol 35, 2017 (suppl; abstr 3005).
3. Validated by a quantitative elemental analysis.
APIM050027: CB-1158 (INCB01158)
CAS No.: 2095732-06-0.
Molecular Formula: C11H22BN3O5.
Molecular Weight: 287.1 (or refer to Certificate of Analysis, batch-spedific).
Purity: 99% by achiral and chiral HPLCs ( detected at 210 nm wavelength).
QC: Achiral and Chiral HPLCs, MS, NMR and Quantitative Elemental Analysis.
Solubility: >100mM in Water
Storage: Refer to Certificate of Analysis.
