CAS NO: | 1448867-41-1 |
包装 | 价格(元) |
10 mM * 1 mL in DMSO | 电议 |
1mg | 电议 |
5mg | 电议 |
10mg | 电议 |
50mg | 电议 |
100mg | 电议 |
200mg | 电议 |
500mg | 电议 |
生物活性 | Siremadlin (NVP-HDM201) is a potent, orally bioavailable and highly specificp53-MDM2interaction inhibitor. | ||||||||||||||||
体外研究 (In Vitro) | Siremadlin (NVP-HDM201) disrupts both human and murine TP53- MDM2 interactions, with nanomolar cellular IC50values, blocking TP53 degradation[1]. | ||||||||||||||||
体内研究 (In Vivo) | Siremadlin (NVP-HDM201) is an imidazolopyrrolidinone analogue, showing a very advantageousin vivoprofile. NVP-HDM201 has recently entered Phase 1 clinical trials in cancer patients[2]. 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[1]. 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]. | ||||||||||||||||
Clinical Trial | |||||||||||||||||
分子量 | 555.41 | ||||||||||||||||
性状 | Solid | ||||||||||||||||
Formula | C26H24Cl2N6O4 | ||||||||||||||||
CAS 号 | 1448867-41-1 | ||||||||||||||||
运输条件 | Room temperature in continental US; may vary elsewhere. | ||||||||||||||||
储存方式 |
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溶解性数据 | In Vitro: DMSO : ≥ 56.75 mg/mL(102.18 mM) *"≥" means soluble, but saturation unknown. 配制储备液
* 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液,再依次添加助溶剂: ——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议您现用现配,当天使用;
以下溶剂前显示的百
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