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Apoptosis Mdm2 Siremadlin

Siremadlin

Catalog No. T5555   CAS 1448867-41-1
Synonyms: NVP-HDM 201,

Siremadlin is a potent, orally bioavailable and highly specific p53-MDM2 interaction inhibitor.

Siremadlin, CAS 1448867-41-1
Pack Size Availability Price/USD Quantity
1 mg In stock 83.00
5 mg In stock 228.00
10 mg In stock 341.00
25 mg In stock 714.00
50 mg In stock 1148.00
1 mL * 10 mM (in DMSO) In stock 352.00
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Biological Description
Chemical Properties
Storage & Solubility Information
Description Siremadlin is a potent, orally bioavailable and highly specific p53-MDM2 interaction inhibitor.
In vitro Siremadlin inhibits both human and murine TP53- MDM2 interactions, with nanomolar cellular IC50 values, blocking TP53 degradation[1]
In vivo Tumors are allografted in large cohorts of mice to assess the pharmacologic effects of Siremadlin (NVP-HDM201). Sixteen out of 21 allograft models are sensitive to Siremadlin (NVP-HDM201) but ultimately relapse under treatment[1]. Siremadlin has recently entered Phase 1 clinical trials in cancer patients[2]. Siremadlin (NVP-HDM201) administered either daily at a low dose or once at a high dose revealed a differentiated engagement of the p53 molecular response. In contrast to the daily low dose treatment regimen, the single high dose Siremadlin (NVP-HDM201) regimen results in a rapid and dramatic induction of p53-dependent PUMA expression and apoptosis. This is consistent with the finding that a single high dose Siremadlin (NVP-HDM201) treatment, administered orally or intravenously, results in a robust and sustained tumor regression. Overall, both daily and once every 3 weeks dosing regimen shows comparable long term efficacy in preclinical studies. The ongoing clinical trial is currently designed to compare both dosing regimens with regard to efficacy and tolerability[3].
Synonyms NVP-HDM 201 ,
Purity
Molecular Weight 555.41
Formula C26H24Cl2N6O4
CAS No. 1448867-41-1

Storage

0-4℃ for short term (days to weeks), or -20℃ for long term (months).

Solubility Information

DMSO: 56.75 mg/mL (102.18 mM)

( < 1 mg/ml refers to the product slightly soluble or insoluble )

Citations

References and Literature
1. Chapeau EA, et al. Resistance mechanisms to TP53-MDM2 inhibition identified by in vivo piggyBac transposon mutagenesis screen in an Arf-/- mouse model. Proc Natl Acad Sci U S A. 2017 Mar 21;114(12):3151-3156. 2. Furet P, et al. Discovery of a novel class of highly potent inhibitors of the p53-MDM2 interaction by structure-based design starting from a conformational argument. Bioorg Med Chem Lett. 2016 Oct 1;26(19):4837-41. 3. Stéphane F, et al. Abstract 1224: Insights into the mechanism of action of NVP-HDM201, a differentiated and versatile Next-Generation small-molecule inhibitor of Mdm2, under evaluation in phase I clinical trials. Insights into the mechanism of action of NVP-HDM201, a differentiated and versatile Next-Generation small-molecule inhibitor of Mdm2, under evaluation in phase I clinical trials. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1224.

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