Drug intelligence / Profile preview

tolinapant + decitabine + cedazuridine

Development stage
Unknown
Lead developer
Astex Pharmaceuticals
Modality
Small Molecules
Administration
Oral
01

Overview

A combination therapy consisting of **tolinapant**, an oral non-peptidomimetic small-molecule antagonist of cellular/X-linked inhibitors of apoptosis proteins (**cIAP1/2** and **XIAP**), with **oral decitabine/cedazuridine**, a fixed-dose combination of the hypomethylating agent decitabine and the cytidine deaminase inhibitor cedazuridine. **Tolinapant** induces apoptosis and necroptosis in T-cell lymphoma. **Decitabine** is a DNA methyltransferase inhibitor that causes hypomethylation and re-expression of silenced genes in tumor cells. **Cedazuridine** increases the oral bioavailability of decitabine by inhibiting cytidine deaminase in the gastrointestinal tract and liver. The combination is being investigated for the treatment of **relapsed/refractory Peripheral T-cell Lymphoma (PTCL)**, with preclinical data suggesting synergistic anti-tumor activity. Tolinapant is not yet approved, but oral decitabine/cedazuridine is approved for myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML)[1][3][5].

Brand names
Inqovi (for decitabine + cedazuridine)Inaqovi (for decitabine + cedazuridine)
Other names
tolinapant + decitabine/cedazuridineASTX660-03 (study/combination reference)decitabine/cedazuridine + tolinapant
02

Targets

XIAP (Baculoviral IAP repeat-containing protein 4)BIRC3 (Baculoviral IAP repeat-containing protein 3)DNMT1 (DNA (cytosine-5)-methyltransferase 1)BIRC2 (Cellular inhibitor of apoptosis protein 1)CDA (Cytidine deaminase)

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