Home Apoptosis MDM2/MDMX inhibitor Siremadlin (HDM201) For research use only.

Siremadlin (HDM201)

Synonyms: NVP-HDM201

Siremadlin (HDM201) is a novel, highly potent and selective inhibitor of the p53-Mdm2 interaction with affinity constant for Mdm2 in the picomolar range and a selectivity ratio greater than 10000-fold vs Mdm4.

Siremadlin (HDM201) Chemical Structure

Siremadlin (HDM201) Chemical Structure

CAS No. 1448867-41-1

Purity & Quality Control

Siremadlin (HDM201) Related Products

Signaling Pathway

MDM2/MDMX Signaling Pathways

MDM2/MDMX Signaling Pathway

Biological Activity

Description Siremadlin (HDM201) is a novel, highly potent and selective inhibitor of the p53-Mdm2 interaction with affinity constant for Mdm2 in the picomolar range and a selectivity ratio greater than 10000-fold vs Mdm4.
Targets
p53-MDM2 interaction [1]
In vitro
In vitro

HDM201 binds to the p53 binding-site of the Mdm2 protein, disrupting the interaction of the two proteins and leading to the activation of the p53 pathway[1].

It induces robust p53-dependent cell cycle arrest and apoptosis in human p53 wild-type tumor cells. HDM201 exhibits highly selectivity across a panel of cancer cell lines[2].
Cell Research Cell lines MES-SA cells
Concentrations 60 nM
Incubation Time 72 h
Method

Cells were treated with the drug for 72 hours.
Experimental Result Images Methods Biomarkers Images PMID
Western blot DUSP6 / p53 / p-p53 / MDM2 / p21 30577494
In Vivo
In vivo

HDM201 displays desirable pharmacokinetic and pharmacodynamic profiles in animals together with excellent oral bioavailability. Application of the compound using various dosing schedules triggers rapid and sustained activation of p53-dependent pharmacodynamic biomarkers resulting in tumor regression in multiple xenografted models of p53 wild-type human cancers[2].
Animal Research Animal Models Uveal melanoma PDX models
Dosages 75 mg/kg
Administration p.o.
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT05447663 Terminated
Acute Myeloid Leukemia|Allogeneic Stem Cell Transplantation
Novartis Pharmaceuticals|Novartis
 February 23 2023 Phase 1|Phase 2
NCT05155709 Active not recruiting
Acute Myeloid Leukemia
Novartis Pharmaceuticals|Novartis
 May 17 2022 Phase 1
NCT05180695 Recruiting
Advanced Soft-tissue Sarcoma|Metastatic Soft-tissue Sarcoma
Centre Leon Berard|Novartis|National Cancer Institute France
 April 15 2022 Phase 1|Phase 2
NCT03940352 Active not recruiting
Acute Myeloid Leukemia (AML)|High-risk Myelodysplastic Syndrome (MDS)
Novartis Pharmaceuticals|Novartis
 June 24 2019 Phase 1

Chemical Information & Solubility

Molecular Weight 555.41 Formula

C26H24Cl2N6O4
CAS No. 1448867-41-1 SDF --
Smiles CC(C)N1C2=C(C(=O)N(C2C3=CC=C(C=C3)Cl)C4=CC(=CN(C4=O)C)Cl)N=C1C5=CN=C(N=C5OC)OC
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 100 mg/mL ( (180.04 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 3 mg/mL

Water : Insoluble


Molecular Weight Calculator

In vivo
Batch:

Add solvents to the product individually and in order.


In vivo Formulation Calculator

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In vivo Formulation Calculator (Clear solution)

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Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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