ASTX-660

dual antagonist of cIAP-XIAP

Also Known As:

ASTX660; ethanone, 1-(6-((4-fluorophenyl)methyl)-2,3-dihydro-5-(hydroxymethyl)-3,3-dimethyl-1H-pyrrolo(3,2-B)pyridin-1-yl)-2-((2R,5R)-5-methyl-2-(((3R)-3-methyl-4-morpholinyl)methyl)-1-piperazinyl)-

Networked: 9 relevant articles (0 outcomes, 5 trials/studies)

Bio-Agent Context: Research Results

Heterocyclic Compounds: 198
- 1-Ring Heterocyclic Compounds

Experts

1.	Smyth, Tomoko: 3 articles (10/2021 - 01/2018)
2.	Schmitt, Nicole C: 3 articles (01/2020 - 01/2018)
3.	Van Waes, Carter: 3 articles (01/2020 - 01/2018)
4.	Ferraldeschi, Roberta: 2 articles (10/2021 - 01/2020)
5.	Jueliger, Simone: 2 articles (10/2021 - 01/2020)
6.	Keer, Harold: 2 articles (10/2021 - 01/2020)
7.	Martins, Vanessa: 2 articles (01/2021 - 01/2018)
8.	Munck, Joanne M: 2 articles (01/2021 - 01/2018)
9.	Allen, Clint T: 2 articles (01/2020 - 01/2018)
10.	Ye, Wenda: 2 articles (01/2020 - 11/2019)

Related Diseases

1.	Squamous Cell Carcinoma of Head and Neck 01/01/2020 - "In this study, we show that ASTX660, an antagonist of cIAP1/2 and XIAP, induces expression of immunogenic cell death (ICD) markers in sensitive HNSCC cell lines in vitro. " 01/01/2020 - "Experiments in syngeneic mouse models of HNSCC showed that ASTX660 can also enhance radiation-induced ICD in vivo. " 11/01/2019 - "IAP1/XIAP antagonist, ASTX660, sensitizes HPV+ HNSCC to TNFα via a mechanism involving restoration of TP53. " 11/01/2019 - "ASTX660 sensitized subsets of HPV- and HPV+ HNSCC cell lines to TNFα and TRAIL. " 01/01/2020 - "Flow cytometry experiments in several human HNSCC cell lines showed that MHC class I (HLA-A,B,C) was reliably upregulated in response to ASTX660 + TNFα, while increases in other antigen processing machinery (APM) components were variable among different cell lines. "
2.	Neoplasms (Cancer) 01/01/2021 - "However, ASTX660 has thus far only been evaluated in few cancer entities. " 01/01/2020 - "These findings suggest that ASTX660 may enhance anti-tumor immunity both by promoting ICD and by enhancing antigen processing and presentation." 01/01/2018 - "Treatment with ASTX660 led to TNFα-dependent induction of apoptosis in various cancer cell lines in vitro, whereas dosing in mice bearing breast and melanoma tumor xenografts inhibited tumor growth. " 01/01/2020 - "On a functional level, ASTX660 also enhanced killing of multiple murine cell lines by cytotoxic tumor-infiltrating lymphocytes, and when combined with XRT, stimulated clonal expansion of antigen-specific T lymphocytes and expression of MHC class I on the surface of tumor cells. " 01/01/2018 - "ASTX660, a Novel Non-peptidomimetic Antagonist of cIAP1/2 and XIAP, Potently Induces TNFα-Dependent Apoptosis in Cancer Cell Lines and Inhibits Tumor Growth."
3.	Colorectal Neoplasms (Colorectal Cancer) 01/01/2021 - "Further clinical studies are warranted to highlight the therapeutic potential of ASTX660 in colorectal cancer." 01/01/2021 - "A novel IAP antagonist tolinapant (ASTX660) potently and rapidly downregulated cIAP1 in colorectal cancer models, demonstrating its robust on-target efficacy. " 01/01/2021 - "Clinical Positioning of the IAP Antagonist Tolinapant (ASTX660) in Colorectal Cancer." 01/01/2021 - "The non-peptidomimetic IAP antagonist ASTX660 sensitizes colorectal cancer cells for extrinsic apoptosis." 01/01/2021 - "Here, we demonstrate that ASTX660 has cell death-promoting activity in colorectal cancer and provide a head-to-head comparison with birinapant, the clinically most advanced peptidomimetic IAP antagonist. "
4.	Lymphoma (Lymphomas) 01/01/2020 - "This first-in-human, phase I study evaluated ASTX660, an oral, small-molecule antagonist of cellular/X-linked inhibitors of apoptosis proteins in patients with advanced solid tumors or lymphoma. " 01/01/2020 - "A Phase I Study of ASTX660, an Antagonist of Inhibitors of Apoptosis Proteins, in Adults with Advanced Cancers or Lymphoma." 01/01/2018 - "ASTX660 is a novel non-peptidomimetic antagonist of cIAP1/2 and XIAP under evaluation in a clinical trial for advanced solid tumors and lymphomas. "
5.	T-Cell Lymphoma (Lymphoma, T Cell) 10/26/2021 - "Tolinapant (ASTX660) is a potent, nonpeptidomimetic antagonist of cellular inhibitor of apoptosis proteins 1 and 2 (cIAP1/2) and X-linked IAP, which is currently being evaluated in a phase 2 study in T-cell lymphoma (TCL) patients. "

Related Drugs and Biologics

1.	Proteins (Proteins, Gene)
2.	Inhibitor of Apoptosis Proteins
3.	Immune Checkpoint Inhibitors
4.	Peptidomimetics
5.	HLA-A Antigens (HLA-A)
6.	Ligands
7.	Cisplatin (Platino)
8.	Antigens
9.	birinapant

Related Therapies and Procedures

1.	Immunotherapy
2.	Radiotherapy
3.	Drug Therapy (Chemotherapy)