Drug intelligence / Profile preview

HDM201 + cytarabine + posaconazole

Development stage
Discontinued
Lead developer
Novartis
Modality
Small Molecules
Administration
Oral (HDM201, Posaconazole), Intravenous (cytarabine; Posaconazole Also Available Iv)
01

Overview

This combination regimen consists of **HDM201 (siremadlin)**, **cytarabine (Ara-C)**, and **posaconazole (Noxafil)**. - **HDM201** is a selective, potent small-molecule inhibitor of the MDM2–p53 protein–protein interaction, stabilizing and activating p53 in wild-type p53 cancer cells, leading to induction of p53 target genes (such as p21 and PUMA), cell cycle arrest, and apoptosis, especially with high-dose pulsed regimens[1][3][5]. - **Cytarabine** (Ara-C) is a cytotoxic antimetabolite chemotherapeutic, inhibiting DNA synthesis by incorporation as a nucleoside analog, leading to cell death primarily in rapidly dividing cells. - **Posaconazole** is a broad-spectrum systemic triazole antifungal agent, inhibiting the enzyme lanosterol 14-alpha demethylase, which is crucial for fungal ergosterol synthesis, used for treatment and prophylaxis of various invasive fungal infections[2][4][6]. This regimen may be used in contexts where intensive chemotherapy is likely to induce severe neutropenia and risk of fungal infections, such as acute myeloid leukemia. It combines targeted therapy (HDM201) and traditional cytotoxic chemotherapy (cytarabine) with antifungal prophylaxis (posaconazole)[1][2][4].

Other names
siremadlincytosine arabinosideAra-Cposaconazole AHCL
02

Targets

DNACYP51A1 (Sterol 14α-demethylase)MDM2 (Mouse double minute 2 homolog)TP53 (Cellular Tumor Antigen p53 R175H)

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