GDC-9545 free base · Synonyms: Giredestrant | RG 6171

Giredestrant (GDC-9545 and RG6171) is a SERD.

For research use only. Not for human or veterinary use.

Target Estrogen Receptor/ERR

Research area Endocrinology Cancer

Purity >98% Stock Inquire

Data Sheet SDS COA

GDC-9545 structure

CAS No.: 1953133-47-5

Download structure (.mol)

Pack sizes & pricing

Size	Price	SKU	Stock
50 mg	USD 498.00	BP-01954-50mg	In stock	Get quote
100 mg	USD 760.00	BP-01954-100mg	In stock	Get quote
250 mg	USD 1,260.00	BP-01954-250mg	In stock	Get quote
500 mg	Inquire	BP-01954-500mg	In stock	Inquire
1 g	Inquire	BP-01954-1g	In stock	Inquire

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Description

Giredestrant (GDC-9545 and RG6171) is a SERD. GDC-9545 is an orally available selective estrogen receptor degrader/downregulator (SERD), with potential antineoplastic activity. Giredestrant has anti-tumor activity.

Biological activity

In Vitro Giredestrant potently inhibits ERα-mediated luciferase activity in T-47D wild-type breast cancer cells, with an IC50 of 0.05 nM[1]. Giredestrant potently degrades ERα in MCF-7 wild-type breast cancer cells, with a DC50 of 0.03 nM and a maximum degradation efficiency of 101%[1]. Giredestrant inhibits the proliferation of MCF-7 wild-type breast cancer cells, with an EC50 of 0.4 nM[1]. Giredestrant (0.1 nM-1 μM; 24 h) induces significant ERα degradation in ER+ breast cancer cell lines including CAMA-1, EFM-19, HCC1500, MCF-7, MDA-MB-134VI, MDA-MB-330 and T-47D starting at a concentration of 0.1 nM, and exhibits higher efficiency than GDC-0810 (HY-12864) and GDC-0927 (HY-111484)[1]. Giredestrant (1 nM; 0.5-24 h) promotes rapid degradation of ERα in MCF-7 breast cancer cells, with a half-life of 1.8 h[1]. In Vivo Giredestrant (0.1-10 mg/kg; p.o.; once daily; for 4 consecutive days) acts as an ERα inverse agonist in vivo, which is evidenced by reduced uterine wet weight and a low cuboidal morphology of uterine epithelial cells at the oral dose of 10 mg/kg per day[1]. Giredestrant (0.1-1 mg/kg; p.o.; once daily; for 29 consecutive days) induces tumor regression in the ESR1Y537S-mutant ER+ breast cancer PDX model, even when administered at a daily oral dose as low as 0.1 mg/kg[1]. Giredestrant (3 mg/kg; p.o.; once daily; for 26 consecutive days) inhibits the growth of wild-type ER+ breast cancer xenografts by up to 79%; when combined with Palbociclib (HY-50767), it induces a maximum tumor regression of 108%[1].

Identifiers

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
InChIKey: GQCXHIKRWBIQMD-AKJBCIBTSA-N

Specifications

MW (average): 522.5533
Formula: C₂₇H₃₁F₅N₄O
CAS No.: 1953133-47-5
Physical state: Solid
Color: Light yellow to yellow
Shipping: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage: Powder -20℃ 2 years; In solvent -20℃ 1 month;

Solubility

Soluble in DMSO, not in water

Documents

References

[1]. 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. J Med Chem. 2021;64(16):11841-11856. doi:10.1021/acs.jmedchem.1c00847

[2]. Liang J, Ingalla ER, Yao X, et al. Giredestrant reverses progesterone hypersensitivity driven by estrogen receptor mutations in breast cancer. Sci Transl Med. 2022;14(663):eabo5959. doi:10.1126/scitranslmed.abo5959

[3]. Chen YC, Yu J, Metcalfe C, et al. Latest generation estrogen receptor degraders for the treatment of hormone receptor-positive breast cancer. Expert Opin Investig Drugs. 2022;31(6):515-529. doi:10.1080/13543784.2021.1983542

[4]. C Metcalfe, et al. Abstract P5-04-07: GDC-9545: A novel ER antagonist and clinical candidate that combines desirable mechanistic and pre-clinical DMPK attributes

Same target

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Same research area

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