Giredestrant
(Synonyms: GDC-9545) 目录号 : GC39630
Giredestrant是一种口服选择性雌激素（ER）受体降解剂。Giredestrant可以诱导雌激素受体配体结合域失活构象，并促进蛋白酶体介导的受体蛋白降解。Giredestrant用于治疗雌激素受体阳性(ER+)乳腺癌。
Cas No.:1953133-47-5
Sample solution is provided at 25 µL, 10mM.
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Giredestrant is an oral selective estrogen receptor (ER) degrader. Giredestrant can induce an inactive conformation of the estrogen receptor ligand binding domain and promoting proteasome-mediated degradation of the receptor protein. Giredestrant is used to treat estrogen receptor-positive (ER+) breast cancer [1-5].
Giredestrant significantly degraded ERα protein and inhibited proliferation at low nanomolar concentrations (0.1nM, 1nM, 10nM, 100nM and 1μM, 24h) in a variety of ER+ breast cancer cell lines (MCF-7, T-47D, CAMA-1 and HCC1500) [5]. In T47D cells, treatment with Giredestrant (50nM, 6d) reduced T47D cell viability [6].
In the HCI-013PDX animal model, Giredestrant (1mg/kg, po, 29d) can strongly induce tumor regression, showing excellent anti-tumor potential [5]. In the HCI-013 PDX model, Giredestrant (30mg/kg, po, 28d) suppressed the mutant ERα-PR proliferation in the mammary gland more so than the standard-of-care agents, tamoxifen and fulvestrant [7]. In the transgenic Esr1 animal model, Giredestrant (30mg/kg, po, 4d) exhibited an antiproliferative response against ESR1 mutant tumors [8].
References:
[1]. Malhi V, Agarwal P, Gates MR, et al. Optimizing Early-stage Clinical Pharmacology Evaluation to Accelerate Clinical Development of Giredestrant in Advanced Breast Cancer. Cancer Research Communications. 2023 Dec 15; 3(12): 2551-2559.
[2]. Martín M, Lim E, Chavez-MacGregor M, et al. Giredestrant for estrogen receptor–positive, HER2-negative, previously treated advanced breast cancer: Results from the randomized, phase II acelERA breast cancer study. Journal of Clinical Oncology. 2024 Jun 20; 42(18): 2149-2160.
[3]. Jhaveri KL, Bellet M, Turner NC, et al. Phase Ia/b study of giredestrant±palbociclib and±luteinizing hormone-releasing hormone agonists in estrogen receptor–positive, HER2-negative, locally advanced/metastatic breast cancer. Clinical Cancer Research. 2024 Feb 16; 30(4): 754-766.
[4]. Pathak N, Oliveira M. New Oral Selective Estrogen Receptor Degraders Redefine Management of Estrogen Receptor–Positive Breast Cancer. Annual Review of Medicine. 2025 Jan 27; 76(1): 243-255.
[5]. Liang J, Zbieg JR, Blake RA, et al. GDC-9545 (Giredestrant): a potent and orally bioavailable selective estrogen receptor antagonist and degrader with an exceptional preclinical profile for ER+ breast cancer. Journal of Medicinal Chemistry. 2021 Jul 12; 64(16): 11841-11846.
[6]. Herrera-Abreu MT, Guan J, Khalid U, et al. Inhibition of GPX4 enhances CDK4/6 inhibitor and endocrine therapy activity in breast cancer. Nature Communications. 2024 Nov 5; 15(1): 9550.
[7]. Liang J, Ingalla ER, Yao X, et al. Giredestrant reverses progesterone hypersensitivity driven by estrogen receptor mutations in breast cancer. Science Translational Medicine. 2022 Sep 21; 14(663): eabo5959.
[8]. Liang J, Yao X, Aouad P, et al. ERα dysfunction caused by ESR1 mutations and therapeutic pressure promotes lineage plasticity in ER+ breast cancer. Nature Cancer. 2025 Jan 13: 1-5.
Giredestrant是一种口服选择性雌激素（ER）受体降解剂。Giredestrant可以诱导雌激素受体配体结合域失活构象，并促进蛋白酶体介导的受体蛋白降解。Giredestrant用于治疗雌激素受体阳性(ER+)乳腺癌 [1-5]。
Giredestrant在低纳摩尔浓度（0.1nM、1nM、10nM、100nM和1μM，24h）下，显著降解ERα蛋白，并抑制多种ER+乳腺癌细胞系（MCF-7、T-47D、CAMA-1 和 HCC1500）的增殖 [5]。在T47D细胞中，用Giredestrant（50nM，6d）治疗可使T47D细胞活力降低 [6]。
在HCI-013PDX动物模型中，Giredestrant（1mg/kg，po，29d）可强烈诱导肿瘤消退，显示出优异的抗肿瘤潜力 [5]。在HCI-013PDX模型中，Giredestrant（30mg/kg，po，28d）对乳腺中突变型ERα-PR增殖的抑制作用优于标准治疗药物他莫昔芬和氟维司群 [7]。在转基因Esr1动物模型中，Giredestrant（30mg/kg，po，4d）表现出对ESR1突变型肿瘤的抗增殖作用 [8]。
| Cell experiment [1]: | |
Cell lines | MCF-7 cells |
Preparation Method | MCF-7 cells were cultured in RPMI 1640 containing 10% FBS, in poly-lysine coated 384 well tissue culture plates for 24h and then treated with different concentrations of Giredestrant for 24h. |
Reaction Conditions | 0.1nM, 1nM, 10nM, 100nM and 1μM; 24h |
Applications | Giredestrant significantly degraded ERα protein and inhibited proliferation at low nanomolar concentrations (0.1nM, 1nM, 10nM, 100nM and 1μM, 24h) in MCF-7. |
| Animal experiment [2]: | |
Animal models | HCI-013 PDX model |
Preparation Method | Giredestrant was administered by oral gavage in HCI-013 PDX model at a dose of 30mg/kg once daily in a volume of 100μL per mouse for 28d. |
Dosage form | 30mg/kg; po; 28d |
Applications | Giredestrant suppressed the mutant ERα-PR proliferation in the mammary gland more so than the standard-of-care agents, tamoxifen and fulvestrant. |
References: | |
| Cas No. | 1953133-47-5 | SDF | |
| 别名 | GDC-9545 | ||
| Canonical SMILES | OCC(F)(F)CN([C@@H]1C2=C(F)C=C(NC3CN(CCCF)C3)C=C2F)[C@H](C)CC4=C1NC5=C4C=CC=C5 | ||
| 分子式 | C27H31F5N4O | 分子量 | 522.55 |
| 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 | 1.9137 mL | 9.5685 mL | 19.1369 mL |
| 5 mM | 0.3827 mL | 1.9137 mL | 3.8274 mL |
| 10 mM | 0.1914 mL | 0.9568 mL | 1.9137 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。
Quality Control & SDS
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- Purity: >99.50%
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