ORIC-101
目录号 : GC65370
ORIC-101 是一种有效、选择性的糖皮质激素受体 (glucocorticoid receptor) 拮抗剂，EC50 值为 5.6 nM。抗癌作用。
Cas No.:2222344-98-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
ORIC-101 is a highly potent and selective glucocorticoid receptor antagonist, with an EC50 of 5.6 nM. Anti-cancer activity.
ORIC-101 shows markedly reduced androgen receptor agonism (EC50, 2500 nM) and CYP2C8 and CYP2C9 inhibition profiles (IC50, >10 μM)[1].ORIC-101 (1-1000 nM) dose-dependently reduces the expression of n GR-mediated target gene (FKBP5 and GILZ), with IC50s of 17.2 and 21.2 nM, respectively[1].
ORIC-101 (75 mg/kg, P.O. twice a day for 16-22 days) enhances the anti-tumor activity in combination with gemcitabine and carboplatin in OVCAR5 xenograft tumor in cortisol-treated mice[1].
[1]. Rew Y, et al. Discovery of a Potent and Selective Steroidal Glucocorticoid Receptor Antagonist (ORIC-101). J Med Chem. 2018 Sep 13;61(17):7767-7784.
| Cas No. | 2222344-98-9 | SDF | Download SDF |
| 分子式 | C34H47NO2 | 分子量 | 501.74 |
| 溶解度 | 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 | 1.9931 mL | 9.9653 mL | 19.9306 mL |
| 5 mM | 0.3986 mL | 1.9931 mL | 3.9861 mL |
| 10 mM | 0.1993 mL | 0.9965 mL | 1.9931 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。
Discovery of a Potent and Selective Steroidal Glucocorticoid Receptor Antagonist (ORIC-101)
J Med Chem 2018 Sep 13;61(17):7767-7784.PMID:30091920DOI:10.1021/acs.jmedchem.8b00743.
The glucocorticoid receptor (GR) has been linked to therapy resistance across a wide range of cancer types. Preclinical data suggest that antagonists of this nuclear receptor may enhance the activity of anticancer therapy. The first-generation GR antagonist mifepristone is currently undergoing clinical evaluation in various oncology settings. Structure-based modification of mifepristone led to the discovery of ORIC-101 (28), a highly potent steroidal GR antagonist with reduced androgen receptor (AR) agonistic activity amenable for dosing in androgen receptor positive tumors and with improved CYP2C8 and CYP2C9 inhibition profile to minimize drug-drug interaction potential. Unlike mifepristone, 28 could be codosed with chemotherapeutic agents readily metabolized by CYP2C8 such as paclitaxel. Furthermore, 28 demonstrated in vivo antitumor activity by enhancing response to chemotherapy in the GR+ OVCAR5 ovarian cancer xenograft model. Clinical evaluation of safety and therapeutic potential of 28 is underway.
In Vivo Profiling with 18F-YJH08 Reveals Diverse Tissue Patterns of Antagonist/Glucocorticoid Receptor Interactions
Mol Pharm 2022 Feb 7;19(2):704-709.PMID:35049307DOI:10.1021/acs.molpharmaceut.1c00833.
Demonstrating target engagement in vivo is an important milestone in drug development, both to establish on target, on tissue interactions but also to identify potentially undesirable off tissue binding. The glucocorticoid receptor (GR) is a long-studied yet vexing drug target that has recently re-emerged as a potential druggable driver of many solid tumor types including breast and prostate cancer, and several antagonists are currently in early phase clinical trials. Since GR is also ubiquitously expressed in normal tissues, understanding antagonist/GR interactions in normal tissues and tumor is crucial to defining a therapeutic index. Herein, we demonstrate that the GR radioligand 18F-YJH08 can map drug/GR engagement in vivo. Profiling target engagement in vivo showed that the GR antagonists RU486 (mifepristone) and CORT125281 engaged GR in fewer normal tissues compared to ORIC-101 or the agonist dexamethasone. Furthermore, 18F-YJH08 detected GR in human prostate cancer tumor models and measured receptor binding by RU486. In summary, these data show for the first time that antagonist/GR interactions can be measured in vivo with 18F-YJH08, a finding with clinical relevance as GR antagonists and 11C-YJH08 are currently in clinical trials.