AG-636
目录号 : GC62470
A DHODH inhibitor
Cas No.:1623416-31-8
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
AG-636 is a dihydroorotate dehydrogenase (DHODH) inhibitor (IC50 = 17 nM).1 It increases levels of ureidosuccinic acid and DHO, pyrimidine biosynthesis metabolites upstream of DHODH, in a panel of six cell lines when used at a concentration of 1 ?M. AG-636 (100 mg/kg) induces complete tumor stasis in an OCI-Ly19 diffuse large B cell lymphoma (DLBCL) mouse xenograft model and complete tumor regression in a Z-138 ibrutinib-resistant mantle cell lymphoma mouse xenograft model. It also increases DHO levels and reduces pyrimidine levels in Z-138 and JeKo-1 lymphoma mouse xenograft models.
1.McDonald, G., Chubukov, V., Coco, J., et al.Selective vulnerability to pyrimidine starvation in hematologic malignancies revealed by AG-636, a novel clinical-stage inhibitor of dihydroorotate dehydrogenaseMol. Cancer Ther.19(12)2502-2515(2020)
| Cas No. | 1623416-31-8 | SDF | |
| 分子式 | C21H17N3O2 | 分子量 | 343.38 |
| 溶解度 | DMSO : 31.25 mg/mL (91.01 mM; Need ultrasonic) | 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 | 2.9122 mL | 14.5611 mL | 29.1223 mL |
| 5 mM | 0.5824 mL | 2.9122 mL | 5.8245 mL |
| 10 mM | 0.2912 mL | 1.4561 mL | 2.9122 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。
Selective Vulnerability to Pyrimidine Starvation in Hematologic Malignancies Revealed by AG-636, a Novel Clinical-Stage Inhibitor of Dihydroorotate Dehydrogenase
Mol Cancer Ther 2020 Dec;19(12):2502-2515.PMID:33082276DOI:10.1158/1535-7163.MCT-20-0550
Agents targeting metabolic pathways form the backbone of standard oncology treatments, though a better understanding of differential metabolic dependencies could instruct more rationale-based therapeutic approaches. We performed a chemical biology screen that revealed a strong enrichment in sensitivity to a novel dihydroorotate dehydrogenase (DHODH) inhibitor, AG-636, in cancer cell lines of hematologic versus solid tumor origin. Differential AG-636 activity translated to the in vivo setting, with complete tumor regression observed in a lymphoma model. Dissection of the relationship between uridine availability and response to AG-636 revealed a divergent ability of lymphoma and solid tumor cell lines to survive and grow in the setting of depleted extracellular uridine and DHODH inhibition. Metabolic characterization paired with unbiased functional genomic and proteomic screens pointed to adaptive mechanisms to cope with nucleotide stress as contributing to response to AG-636. These findings support targeting of DHODH in lymphoma and other hematologic malignancies and suggest combination strategies aimed at interfering with DNA-damage response pathways.