Siremadlin

SKU: orb1301697

Description

Siremadlin (NVP-HDM201) is a potent, specific, and orally bioavailable small molecule inhibitor of the p53-MDM2 interaction. It is used in cancer research to reactivate p53 in vitro and has demonstrated antitumor efficacy in vivo in xenograft models of wild-type p53 tumors.

Research Area

Cell Biology, Protein Biochemistry

Key Properties

• CAS Number: 1448867-41-1
• MW: 555.41
• Purity: 97.77% (May vary between batches)
• Formula: C₂₆H₂₄Cl₂N₆O₄
• SMILES: COc1ncc(-c2nc3C(=O)N([C@H](c3n2C(C)C)c2ccc(Cl)cc2)c2cc(Cl)cn(C)c2=O)c(OC)n1
• Target: MDM-2/p53,E1/E2/E3 Enzyme
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (3.6 mM);DMSO:56.75 mg/mL (102.18 mM)

Bioactivity

• 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. Siremadlin has recently entered Phase 1 clinical trials in cancer patients. 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.
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• In Vitro:
  Siremadlin inhibits both human and murine TP53- MDM2 interactions, with nanomolar cellular IC50 values, blocking TP53 degradation

Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

E1Enzyme, E2 conjugating enzyme, E2 Enzyme, E1/E2/E3 Enzyme, E1 Enzyme, E1 activating enzyme, inhibit, p53-MDM2, NVP-HDM 201, NVP-HDM201, NVP-HDM-201, HDM201, HDM-201, HDM 201, Inhibitor, MDM-2/p53, E3 Enzyme, E2Enzyme, E3 ligating enzyme, E3Enzyme, Siremadlin, Ubiquitin ligase, Ubiquitin conjugating enzyme, Ubiquitin activating enzyme

Compound Identifiers

PubChem CID

71678098