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.
GDC-9545 structure
CAS No.: 1953133-47-5
Pack sizes & pricing
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