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Siremadlin (HDM201) MDM2/MDMX inhibitor

Name: Siremadlin (HDM201)
Brand: Selleck Chemicals
SKU: S8606
Availability: InStock
Rating: 5 (6 reviews)

Cat.No.S8606

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

Chemical Structure

Molecular Weight: 555.41

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Quality Control

Batch: Purity: 99.83%

99.83

Related Targets	Bcl-2 Caspase PD-1/PD-L1 Ferroptosis p53 Apoptosis related Synthetic Lethality STAT TNF-alpha Ras
Other MDM2/MDMX Inhibitors	Nutlin-3 RG-7112 Nutlin-3a Brigimadlin Idasanutlin (RG7388) SAR405838 NSC 207895 NVP-CGM097 Nutlin-3b YH239-EE

Solubility

In vitro
Batch:

DMSO : 100 mg/mL (180.04 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 3 mg/mL

Water : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
Mass value Mass unit	Concentration value Concentration unit	Volume value Volume unit	Molecular weight (g/mol)

Dilution Calculator Molecular Weight Calculator

In vivo batch selection In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	5.000mg/ml (9.00mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL PEG300, mix evenly to clarify it; add 50 μL Tween80 to the above system, mix evenly to clarify it; then continue to add 500 μL ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	1.250mg/ml (2.25mM)	Taking the 1 mL working solution as an example, add 50 μL of 25 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg

Average weight of animals: g

Dosing volume per animal: μL

Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO

% Tween 80

% ddH₂O

% DMSO

Calculation results:

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.

Chemical Information, Storage & Stability

Molecular Weight	555.41	Formula	C₂₆H₂₄Cl₂N₆O₄	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	1448867-41-1	--		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	NVP-HDM201			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

Read more about storage stability stock solution CAS number SMILES

Mechanism of Action

Targets/IC₅₀/Ki	p53-MDM2 interaction
In vitro	Siremadlin (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. It induces robust p53-dependent cell cycle arrest and apoptosis in human p53 wild-type tumor cells, and exhibits highly selectivity across a panel of cancer cell lines.
In vivo	Siremadlin (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.
References	[1] http://cancerres.aacrjournals.org/content/76/14_Supplement/1239 [2] http://cancerres.aacrjournals.org/content/76/14_Supplement/4855 [3] https://pubmed.ncbi.nlm.nih.gov/35008180/ [4] https://pubmed.ncbi.nlm.nih.gov/31927215/

Applications

Methods	Biomarkers	Images	PMID
Western blot	DUSP6 / p53 / p-p53 / MDM2 / p21		30577494

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2026-06-22)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT05180695	ACTIVE_NOT_RECRUITING	Advanced Soft-tissue Sarcoma; Metastatic Soft-tissue Sarcoma	Centre Leon Berard	2022-04-15	PHASE1; PHASE2
NCT04116541	RECRUITING	Malignant Solid Tumor	Centre Leon Berard	2020-01-28	PHASE2
NCT03940352	TERMINATED	Acute Myeloid Leukemia (AML); High-risk Myelodysplastic Syndrome (MDS)	Novartis Pharmaceuticals	2019-06-24	PHASE1
NCT05155709	COMPLETED	Acute Myeloid Leukemia	Novartis Pharmaceuticals	2022-05-17	PHASE1
NCT05447663	TERMINATED	Acute Myeloid Leukemia; Allogeneic Stem Cell Transplantation	Novartis Pharmaceuticals	2023-02-23	PHASE1; PHASE2
NCT05599932	COMPLETED	Hepatic Impairment	Novartis Pharmaceuticals	2022-12-02	PHASE1

Tech Support

Handling Instructions

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