推荐产品
质量水平
方案
≥98% (HPLC)
储存条件
desiccated
颜色
white to beige
溶解性
DMSO: 2 mg/mL, clear
储存温度
−20°C
SMILES字符串
O=C([C@@H]1N[C@@H](CC(C)(C)C)[C@@]2(C(NC3=C2C=CC(Cl)=C3)=O)[C@H]1C4=CC=CC(Cl)=C4F)N[C@@H]5CC[C@H](CC5)O
InChI
1S/C29H34Cl2FN3O3/c1-28(2,3)14-22-29(19-12-7-15(30)13-21(19)34-27(29)38)23(18-5-4-6-20(31)24(18)32)25(35-22)26(37)33-16-8-10-17(36)11-9-16/h4-7,12-13,16-17,22-23,25,35-36H,8-11,14H2,1-3H3,(H,33,37)(H,34,38)/t16-,17-,22-,23-,25+,29+/m0/s1
InChI key
IDKAKZRYYDCJDU-HBMMIIHUSA-N
生化/生理作用
Orally available, highly potent and selective Mdm2 (Hdm2) inhibitor that blocks cancer growth in a wild-type p53-dependent manner both in vitro and in vivo.
SAR405838 (MI-77301) is an orally available (F = 67%/mouse, 48%/rat; 10 mg/kg p.o.), highly potent and selective Mdm2 (Hdm2) inhibitor (human Mdm2 Ki = 0.88 nM; no binding at 10 μM to Bcl-2, Bcl-xL, Mcl-1, Mdmx; no inhibition against >200 receptors/enzymes) that upregulates wild-type p53 activity (EC50 = 300-600 nM; SJSA-1) by blocking Mdm2-p53 interaction and Mdm2-mediated p53 degradation with 5-10-times higher potency than MI-219 and nutlin-3a. SAR405838 inhibits cancer growth in a wild-type p53-dependent manner both in cultures (IC50 = 89 nM/RS4;11, 92 nM/SJSA-1, 200 nM/HCT-116, 270 nM/LANCaP) and in xenograft models in vivo (50-200 mg/kg single or daily p.o. dosing).
储存分类代码
11 - Combustible Solids
WGK
WGK 3
闪点(°F)
Not applicable
闪点(°C)
Not applicable
法规信息
新产品
历史批次信息供参考:
Liye He et al.
Cancer research, 78(9), 2407-2418 (2018-02-28)
The molecular pathways that drive cancer progression and treatment resistance are highly redundant and variable between individual patients with the same cancer type. To tackle this complex rewiring of pathway cross-talk, personalized combination treatments targeting multiple cancer growth and survival
Maja de Jonge et al.
European journal of cancer (Oxford, England : 1990), 76, 144-151 (2017-03-23)
In tumours with wild-type TP53, the tumour-suppressive function of p53 is frequently inhibited by HDM2. This phase I, dose-escalating study investigated the maximum tolerated dose (MTD), safety, pharmacokinetics and pharmacodynamics of SAR405838, an HDM2 inhibitor, in patients with advanced solid tumours (NCT01636479).
A N Hata et al.
Oncogene, 36(47), 6581-6591 (2017-08-08)
There are currently no effective targeted therapies for KRAS mutant cancers. Therapeutic strategies that combine MEK inhibitors with agents that target apoptotic pathways may be a promising therapeutic approach. We investigated combining MEK and MDM2 inhibitors as a potential treatment
Lunxi Liang et al.
Cell chemical biology, 25(6), 761-774 (2018-04-24)
Many cancer-related proteins are controlled by composite post-translational modifications (PTMs), but prevalent strategies only target one type of modification. Here we describe a designed peptide that controls two types of modifications of the p53 tumor suppressor, based on the discovery
Kate Lynn J Bill et al.
Clinical cancer research : an official journal of the American Association for Cancer Research, 22(5), 1150-1160 (2015-10-18)
Dedifferentiated liposarcoma (DDLPS) is an aggressive malignancy that can recur locally or disseminate even after multidisciplinary care. Genetically amplified and expressed MDM2, often referred to as a "hallmark" of DDLPS, mostly sustains a wild-type p53 genotype, substantiating the MDM2:p53 axis
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