Siremadlin

CAS号

1448867-41-1

分子式

C26H24Cl2N6O4

主要靶点

E1/E2/E3 Enzyme

仅限科研使用

Cat No : CM05042

Print datasheet

Synonyms

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



产品信息

CAS号 1448867-41-1
分子式 C26H24Cl2N6O4
主要靶点 E1/E2/E3 Enzyme
主要通路 泛素化
分子量 555.41
纯度 98.04%, 此纯度可做参考,具体纯度与批次有关系,可咨询客服
储存条件 Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice.
别名 E3 ligating enzyme|E3Enzyme|E2Enzyme|E3 Enzyme|E2 conjugating enzyme|E2 Enzyme|E1Enzyme|E1/E2/E3 Enzyme|E1 activating enzyme|E1 Enzyme|HDM 201|HDM201|HDM-201|Siremadlin|Ubiquitin activating enzyme|Ubiquitin conjugating enzyme|Ubiquitin ligase|MDM-2/p53|inhibit|Inhibitor|NVP-HDM 201|NVP-HDM201|NVP-HDM-201|p53-MDM2

体内活性

为评价Siremadlin (NVP-HDM201)的药理作用,大批量的小鼠中进行异种移植肿瘤模型研究。21个异种移植模型中有16个对Siremadlin (NVP-HDM201)敏感,但最终在治疗下复发[1]。Siremadlin最近进入了癌症患者的第一阶段临床试验[2]。Siremadlin (NVP-HDM201)以每日低剂量或一次性高剂量给药,揭示了p53分子应答的差异化激活。与每日低剂量给药方案相比,一次性高剂量Siremadlin (NVP-HDM201)方案导致了p53依赖性PUMA表达和细胞凋亡的快速且显著诱导。这与发现一致,一次性高剂量Siremadlin (NVP-HDM201)治疗,无论是口服还是静脉注射,均能导致肿瘤的强效且持续回退。总体而言,每日给药和每三周一次给药方案在临床前研究中显示了相当的长期疗效。正在进行的临床试验旨在比较两种给药方案的疗效和耐受性[3]。

体外活性

Siremadlin有效抑制人类和小鼠的TP53-MDM2相互作用,以纳摩尔级别的细胞IC50值阻止TP53的降解[1]。

溶解度

DMSO:56.75 mg/mL (102.18 mM)

参考文献

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.

The molarity calculator equation

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

质量   浓度   体积   分子量 *
=
×
×

The dilution calculator equation

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
This equation is commonly abbreviated as: C1V1 = C2V2

浓度 (start) × 体积 (start) = 浓度 (final) × 体积 (final)
×
=
×
C1   V1   C2   V2