Drug intelligence / Profile preview

decitabine + venetoclax + selinexor

Development stage
Unknown
Lead developer
Karyopharm Therapeutics
Modality
Small Molecules
Administration
Intravenous, Oral
01

Overview

This drug is a combination therapy consisting of three agents—decitabine, venetoclax, and selinexor—used primarily in the treatment of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), particularly in patients who are newly diagnosed but unfit for intensive chemotherapy or those with relapsed/refractory disease. - Decitabine is a hypomethylating agent that incorporates into DNA and inhibits DNA methyltransferase, leading to hypomethylation of DNA and reactivation of silenced genes involved in cell cycle regulation. - Venetoclax is a selective BCL-2 inhibitor that promotes apoptosis by inhibiting the anti-apoptotic protein BCL-2, which is often overexpressed in cancer cells. - Selinexor is an oral selective inhibitor of nuclear export (SINE) compound that specifically blocks exportin 1 (XPO1/CRM1), resulting in nuclear retention and activation of tumor suppressor proteins, cell cycle arrest, inhibition of DNA damage repair, modulation of NF-kB expression, and induction of apoptosis. The combination has shown promising efficacy with manageable safety profiles; reported adverse events include mild to moderate pulmonary infection, thrombocytopenia, pancytopenia, and diarrhea[2][6]. The regimen aims to exploit synergistic mechanisms for improved outcomes in high-risk hematologic malignancies.

Other names
DVS
02

Targets

DNMT1 (DNA (cytosine-5)-methyltransferase 1)XPO1 (Exportin-1)BCL-2 (BCL-2 family)

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