HDM201 (Siremadlin)

Catalog No.S8606 Synonyms: NVP-HDM201

For research use only.

HDM201 (Siremadlin, NVP-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.

HDM201 (Siremadlin) Chemical Structure

CAS No. 1448867-41-1

Selleck's HDM201 (Siremadlin) has been cited by 2 Publications

Purity & Quality Control

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Biological Activity

Description HDM201 (Siremadlin, NVP-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

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].

Assay
Methods Test Index PMID
Western blot DUSP6 / p53 / p-p53 / MDM2 / p21 30577494
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].

Protocol (from reference)

Solubility (25°C)

In vitro

Chemical Information

Molecular Weight 555.41
Formula

C26H24Cl2N6O4

CAS No. 1448867-41-1
Storage 3 years -20°C powder
2 years -80°C in solvent
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

In vivo Formulation Calculator (Clear solution)

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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.

Molarity Calculator

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Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT05180695 Recruiting Drug: Pazopanib|Drug: HDM201 Advanced Soft-tissue Sarcoma|Metastatic Soft-tissue Sarcoma Centre Leon Berard|Novartis|National Cancer Institute France April 15 2022 Phase 1|Phase 2
NCT03940352 Recruiting Drug: HDM201|Biological: MBG453|Drug: Venetoclax Acute Myeloid Leukemia (AML)|High-risk Myelodysplastic Syndrome (MDS) Novartis Pharmaceuticals|Novartis June 24 2019 Phase 1
NCT02601378 Terminated Drug: LXS196|Drug: LXS196 and HDM201 Uveal Melanoma Novartis Pharmaceuticals|Novartis February 1 2016 Phase 1
NCT02343172 Completed Drug: HDM201|Drug: LEE011 Liposarcoma Novartis Pharmaceuticals|Novartis March 13 2015 Phase 1

(data from https://clinicaltrials.gov, updated on 2022-08-01)

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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