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CHOP + duvelisib + 5-azacitidine

Development stage
Preclinical
Lead developer
Verastem Oncology
Modality
Orthosteric Ligands → Classical Binding Small Molecules → Small Molecules, Covalent Small Molecules → Small Molecules, Nucleic Acid-Directed Small Molecules → Small Molecules
Administration
Intravenous, Oral, Subcutaneous
01

Overview

CHOP + duvelisib + 5-azacitidine is an investigational combination regimen composed of three distinct therapies: - **CHOP** is a standard chemotherapy regimen consisting of cyclophosphamide (an alkylating agent that cross-links DNA), doxorubicin (an anthracycline that intercalates DNA and inhibits topoisomerase II), vincristine (a vinca alkaloid that inhibits microtubule formation), and prednisone or prednisolone (corticosteroids with lympholytic effects)[3][4][5]. - **Duvelisib** is an oral small molecule inhibitor targeting phosphoinositide 3-kinase delta and gamma isoforms, disrupting B-cell and T-cell receptor signaling pathways critical for malignant cell survival[6][9]. - **5-Azacitidine** (azacitidine) is a pyrimidine nucleoside analogue with dual mechanisms as a cytotoxic antimetabolite incorporated into RNA/DNA, disrupting their function, and as a hypomethylating agent inhibiting DNA methyltransferases, leading to impaired gene silencing in cancer cells[7][10]. This combination aims to leverage the cytotoxicity of CHOP, the targeted pathway inhibition by duvelisib, and the epigenetic modulation by azacitidine. It may be under investigation for hematologic malignancies such as lymphoma or leukemia.

Other names
CHOP + duvelisib + 5-azacitidineCHOP + duvelisib + azacitidineCHOP-X2CHOP-X-2CHOP-X 2
02

Targets

TUBB (Tubulin (alpha and beta subunits))TOP2A (DNA topoisomerase II)DNMT (DNA methyltransferase)GR (Glucocorticoid receptor)DNAPIK3CD (Phosphatidylinositol 3-kinase delta)PIK3CG (Phosphatidylinositol 4,5-bisphosphate 3-kinase gamma)

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