BI-4924
目录号 : GC35515
BI-4924 是一种亲脂性，与血浆蛋白高度结合的选择性磷酸甘油酸脱氢酶 (PHGDH) 抑制剂 (IC50=3 nM)，具有优异的微粒体和肝细胞稳定性。胞内捕获 BI-4924 可破坏丝氨酸生物合成，作用 72 小时的 IC50 为 2200 nM。
Cas No.:2244452-09-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
BI-4924 is a lipophilic, highly plasma protein bound selective phosphoglycerate dehydrogenase (PHGDH) inhibitor (IC50=3 nM) with excellent microsomal, as well as hepatocytic stability. Intracellular trapping of BI-4924 disrupts serine biosynthesis with an IC50 of 2200 nM at 72 h[1]. PHGDH[1]
BI-4924 is a highly potent co-factor nicotinamide adenine dinucleotide (NADH/NAD+)-competitive PHGDH inhibitor. BI-4924 shows high selectivity against the majority of other dehydrogenase targets[1].
[1]. Weinstabl H, et al. Intracellular Trapping of the Selective Phosphoglycerate Dehydrogenase (PHGDH) Inhibitor BI-4924 Disrupts Serine Biosynthesis. J Med Chem. 2019 Jul 31.
| Cas No. | 2244452-09-1 | SDF | |
| Canonical SMILES | O=C(O)CS(=O)(C1=CC=C([C@H](NC(C(N2C)=CC3=C2C=C(C)C(Cl)=C3Cl)=O)CO)C=C1)=O | ||
| 分子式 | C21H20Cl2N2O6S | 分子量 | 499.36 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
| General tips | 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。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.0026 mL | 10.0128 mL | 20.0256 mL |
| 5 mM | 0.4005 mL | 2.0026 mL | 4.0051 mL |
| 10 mM | 0.2003 mL | 1.0013 mL | 2.0026 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Intracellular Trapping of the Selective Phosphoglycerate Dehydrogenase (PHGDH) Inhibitor BI-4924 Disrupts Serine Biosynthesis
J Med Chem 2019 Sep 12;62(17):7976-7997.PMID:31365252DOI:10.1021/acs.jmedchem.9b00718
Phosphoglycerate dehydrogenase (PHGDH) is known to be the rate-limiting enzyme in the serine synthesis pathway in humans. It converts glycolysis-derived 3-phosphoglycerate to 3-phosphopyruvate in a co-factor-dependent oxidation reaction. Herein, we report the discovery of BI-4916, a prodrug of the co-factor nicotinamide adenine dinucleotide (NADH/NAD+)-competitive PHGDH inhibitor BI-4924, which has shown high selectivity against the majority of other dehydrogenase targets. Starting with a fragment-based screening, a subsequent hit optimization using structure-based drug design was conducted to deliver a single-digit nanomolar lead series and to improve potency by 6 orders of magnitude. To this end, an intracellular ester cleavage mechanism of the ester prodrug was utilized to achieve intracellular enrichment of the actual carboxylic acid based drug and thus overcome high cytosolic levels of the competitive cofactors NADH/NAD+.