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In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
HDM201, also known as Siremadlin or NVP-HDM201, inhibits the Mdm2-p53 protein-protein interaction, with affinity constant for Mdm2 in the picomolar range and a selectivity ratio greater than 10000-fold vs. Mdm4. It binds to the p53 binding-site of the Mdm2 protein, disrupting the interaction of the Mdm2 and p53 proteins as well as leading to the activation of the p53 pathway. Currently, interfering the interaction between the tumor suppressor p53 and its main negative regulator MDM2 has become a therapeutic concept explored to treat cancers.
References:
1. Stachyra-Valat T, Baysang F, D’Alessandro AC, et al. Abstract 1239: NVP-HDM201: Biochemical and biophysical profile of a novel highly potent and selective PPI inhibitor of p53-Mdm2. Cancer Research, 2016, 76(14 Suppl): Abstract nr 1239.
2. Jeay S, Ferretti S, Holzer P, et al. Dose and Schedule Determine Distinct Molecular Mechanisms Underlying the Efficacy of the p53-MDM2 Inhibitor HDM201. Cancer Research, 2018, 78(21): 6257-6267.
Cell lines
Human SJSA-1 cancer cells
Reaction Conditions
Continuous low-dose treatment: 1.5 μmol/L for 7 ~ 10 h; pulsed high-dose treatment: 0.1 μmol/L for 48 ~ 72 h
Applications
Continuous exposure of HDM201 resulted in induction of p21 and delayed accumulation of apoptotic cells. In contrast, high-dose pulses of HDM201 were associated with marked induction of PUMA and a rapid onset of apoptosis.
Animal models
SJSA-1 and HSAX2655 tumor-bearing rats
Dosage form
5 or 27 mg/kg
Orally
HDM201 at 27 mg/kg induced robust increases in p21 and PUMA proteins whereas only p21 protein was increased after the low-dose treatment (5 mg/kg). Single high-dose treatment of HDM201 induced PUMA-associated tumor regression in vivo.
Note
The technical data provided above is for reference only.