HDM-201

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

HDM-201 (NVP-HDM 201, Siremadlin) 是一种高效的 p53-MDM2 相互作用抑制剂，生化 IC50 为 0.13 nM，细胞 IC50 为 90 nM。

HDM-201 (NVP-HDM 201, Siremadlin)?is a highly potent p53-MDM2 interaction inhibitor with biochemical IC50 of 0.13 nM, cellular IC50 of 90 nM; a second generation p53-MDM2 inhibitor that recently entered phase I clinical trial.

Siremadlin (NVP-HDM201) disrupts both human and murine TP53- MDM2 interactions, with nanomolar cellular IC50 values, blocking TP53 degradation.

Siremadlin (NVP-HDM201) is an imidazolopyrrolidinone analogue, showing a very advantageous in vivo profile. NVP-HDM201 has recently entered Phase 1 clinical trials in cancer patients. Constitutive PB mutagenesis in Arf?/? mice provides a collection of spontaneous tumors with characterized insertional genetic landscapes. 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. A comparison of tumors with acquired resistance to Siremadlin (NVP-HDM201) and untreated tumors identified 87 genes that are differentially and significantly targeted by the PB transposon. 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.

NVP-HDM 201 | NVP HDM201 | Siremadlin

Apoptosis

MDM2-p53

MDM2-p53

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1448867-41-1

555.4125

C26H24Cl2N6O4

>98% (HPLC)

DMSO : ≥ 56.75 mg/mL 102.18 mM

O=C1N(C2=CC(Cl)=CN(C)C2=O)[C@@H](C3=CC=C(Cl)C=C3)C4=C1N=C(C5=CN=C(OC)N=C5OC)N4C(C)C

(S)-5-(5-chloro-1-methyl-2-oxo-1,2-dihydropyridin-3-yl)-6-(4-chlorophenyl)-2-(2,4-dimethoxypyrimidin-5-yl)-1-isopropyl-5,6-dihydropyrrolo[3,4-d]imidazol-4(1H)-one

(-20℃)

With Ice Pack

≥ 2 years