Drug intelligence / Profile preview

AMG 397 + azacitidine

Development stage
Unknown
Lead developer
Amgen
Modality
Small Molecules
Administration
Oral (amg 397), Subcutaneous (azacitidine), Intravenous (azacitidine)
01

Overview

AMG 397 + azacitidine is a combination investigational therapy for hematological malignancies such as acute myeloid leukemia (AML). **AMG 397** (murizatoclax) is an orally bioavailable, potent and selective small molecule inhibitor of myeloid cell leukemia 1 (**MCL-1**), an antiapoptotic protein frequently overexpressed in cancer that promotes cell survival. By inhibiting MCL-1, AMG 397 induces apoptosis in malignant cells via activation of BAX and caspase-3[3][2][5]. Azacitidine is a hypomethylating agent that incorporates into DNA and RNA, leading to DNA hypomethylation and cytotoxicity, primarily in abnormal hematopoietic cells. Azacitidine is approved as a standard therapy for myelodysplastic syndromes and for AML in adults unfit for intensive chemotherapy[1]. The combination is studied to exploit potential synergistic effects against AML by targeting two complementary pathways: apoptotic evasion and aberrant epigenetic regulation. *The development of AMG 397 is currently on clinical hold due to a safety signal for cardiac toxicity*[3][5].

Other names
murizatoclaxAMG-397 + azacitidine
02

Targets

DNA/RNA (Cellular Nucleic Acids (DNA and RNA))MCL1 (Myeloid cell leukemia sequence 1)DNMT (DNA methyltransferase)

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