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HDM201 + cytarabine + anthracycline + midostaurin

Development stage
Unknown
Lead developer
Novartis
Modality
Orthosteric Ligands → Classical Binding Small Molecules → Small Molecules, Reversible Covalent Inhibitors → Covalent Small Molecules → Small Molecules, Allosteric Modulators → Classical Binding Small Molecules → Small Molecules, Irreversible Covalent Inhibitors → Covalent Small Molecules → Small Molecules, Nucleic Acid-Directed Small Molecules → Small Molecules
Administration
Intravenous (cytarabine, Anthracycline), Oral (midostaurin, HDM201)
01

Overview

This drug is a **four-drug combination regimen** composed of HDM201 (siremadlin), cytarabine, an anthracycline (such as daunorubicin or idarubicin), and midostaurin. - **HDM201 (siremadlin)** is a **second-generation MDM2-p53 interaction antagonist** that stabilizes p53, promoting p53-dependent apoptosis in malignant cells with wild-type TP53[1][5][3]. - **Cytarabine** is a **pyrimidine nucleoside antimetabolite** that inhibits DNA synthesis, leading to cell death, especially in rapidly dividing cells. - **Anthracyclines** (e.g., daunorubicin, idarubicin) are **topoisomerase II inhibitors** that intercalate DNA and induce DNA breaks, causing apoptosis in cancer cells. - **Midostaurin** is a **multitargeted kinase inhibitor** that inhibits receptor tyrosine kinases including FLT3, c-KIT, and PDGFR, leading to apoptosis in AML cells, particularly those with FLT3 mutations[4][2][6][8][3]. This regimen's primary indication is **acute myeloid leukemia (AML)**, especially in patients with FLT3 mutations and wild-type TP53[3]. It is currently under evaluation in clinical trials for relapsed/refractory AML, with phase I development status[3]. Developers include Novartis.

Brand names
Rydapt (midostaurin)
Other names
HDM201HDM-201HDM 201siremadlincytarabineanthracycline (e.g., daunorubicin, idarubicin)midostaurinPKC412PKC-412PKC 412NVP-PKC412NVP-PKC-412NVP-PKC 412
02

Targets

DNAKIT (c-KIT proto-oncogene receptor tyrosine kinase)VEGFR2 (Vascular endothelial growth factor receptor 2)MDM2 (Mouse double minute 2 homolog)TOP2A (DNA topoisomerase II)PDGFRA (Platelet-derived growth factor receptor alpha)PRKCA (Protein kinase C alpha)FLT3 (Fms related receptor tyrosine kinase 3)

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