ASTX660

SKU: orb1296257

Description

Tolinapant (ASTX660) is an orally active small molecule antagonist of cIAP1/2 and XIAP. It promotes immunogenic cell death (ICD) in sensitive head and neck squamous cell carcinoma (HNSCC) models in vitro, supporting its investigation in cancer immunotherapy and apoptosis research.

Research Area

Cell Biology

Key Properties

• CAS Number: 1799328-86-1
• MW: 539.68
• Purity: 99.85% (May vary between batches)
• Formula: C₃₀H₄₂FN₅O₃
• SMILES: C[C@@H]1CN(CC(=O)N2CC(C)(C)c3nc(CO)c(Cc4ccc(F)cc4)cc23)[C@@H](CN2CCOC[C@H]2C)CN1
• Target: Apoptosis,IAP
• Solubility: 10% DMSO+40% PEG300+5% Tween-80+45% Saline:2 mg/mL (3.71 mM);DMSO:47 mg/mL (87.09 mM)

Bioactivity

• In Vivo:
  METHODS: Tolinapant (ASTX660)(16 mg/kg, oral), XRT (single dose 8 Gy), or a combination of both treated a MEER syngeneic tumor xenograft mouse model. Tumors, spleens, and DLNs were harvested and analyzed for CD8 lymphocytes by flow cytometry. Tumor subpopulations were digested and T cells were magnetically selected and cocultured with inactivated dendritic cells presenting p15E peptide. Subsequent IFN-γ production was quantified using an ELISpot assay. RESULTS The number of CD8+ T cells in the spleen was significantly increased in animals treated with ASTX660 alone and in the subpopulation of animals treated with radiation ± ASTX660 (Figure 3(b)). In the draining lymph nodes of animals treated with XRT alone There was a significant increase in the number of CD8 T lymphocytes and an almost significant increase in the number of CD8 T lymphocytes in animals that received the combination treatment.
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• In Vitro:
  METHODS: Four human HNSCC cell lines (3 HPV-, 1 HPV+) were treated with IFN-γ (positive control, 10 ng/mL), TNFα (20 ng/mL), Tolinapant (ASTX660) (500 nM, 1 μM), and ASTX660 (250 nM, 500 nM, 1 μM) + TNFα for 48 hours, and then the intracellular APM components were analyzed by flow cytometry. RESULTS In all four cell lines, HLA-A, B, and C expression was consistently increased under ASTX660 + TNFα treatment. ASTX660 + TNFα may enhance tumor cell killing. METHODS: DLD1, HCT116, and SW48 were treated with ASTX660 (0.04, 0.2, 1 μM, 24 hours). After washing and cell lysis, western blot analysis was performed using antibodies specific for the indicated proteins. RESULTS ASTX660 concentrations as low as 40 nM were sufficient to rapidly reduce cIAP2 (but not cIAP1) levels.
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Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

XIAP, inhibit, Inhibitor, IAP, ASTX 660, ASTX660, ASTX-660, cIAP

Compound Identifiers

PubChem CID

118169620