Siremadlin 是一种有效的、可口服的、高度特异性的 p53-Mdm2 相互作用抑制剂。

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

Siremadlin inhibits both human and murine TP53- MDM2 interactions, with nanomolar cellular IC50 values, blocking TP53 degradation[1]

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].

1448867-41-1

C26H24Cl2N6O4

555.42

NVP-HDM 201

DMSO:56.75 mg/mL (102.18 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years