Siremadlin (HDM201)

Catalog No.S8606 Batch:S860601

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Technical Data

Formula

C26H24Cl2N6O4
Molecular Weight 555.41 CAS No. 1448867-41-1
Solubility (25°C)* In vitro DMSO 100 mg/mL (180.04 mM)
Ethanol 3 mg/mL (5.4 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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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

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].
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)

Cell Assay:

[3]
  • Cell lines

    MES-SA cells

  • Concentrations

    60 nM

  • Incubation Time

    72 h

  • Method

    Cells were treated with the drug for 72 hours.
Animal Study:

[4]
  • Animal Models

    Uveal melanoma PDX models

  • Dosages

    75 mg/kg

  • Administration

    p.o.

Selleck's Siremadlin (HDM201) has been cited by 5 publications

Helicobacter pylori-induced NAT10 stabilizes MDM2 mRNA via RNA acetylation to facilitate gastric cancer progression [ J Exp Clin Cancer Res, 2023, 42(1):9] PubMed: 36609449
Primary head and neck cancer cell cultures are susceptible to proliferation of Epstein-Barr virus infected lymphocytes [ BMC Cancer, 2023, 23(1):47] PubMed: 36639629
p53 Pathway Inactivation Drives SMARCB1-deficient p53-wildtype Epithelioid Sarcoma Onset Indicating Therapeutic Vulnerability Through MDM2 Inhibition [ Mol Cancer Ther, 2022, 21(11):1689-1700] PubMed: 36099437
Tipping Growth Inhibition into Apoptosis by Combining Treatment with MDM2 and WIP1 Inhibitors in p53WT Uterine Leiomyosarcoma [ Cancers (Basel), 2021, 14(1)14] PubMed: 35008180
Preclinical Evaluation of Drug Combinations Identifies Co-Inhibition of Bcl-2/XL/W and MDM2 as a Potential Therapy in Uveal Melanoma [ Eur J Cancer, 2020, 126:93-103] PubMed: 31927215

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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