Giredestrant

Giredestrant
Identifiers
  • 3-[(1R,3R)-1-[2,6-difluoro-4-[[1-(3-fluoropropyl)azetidin-3-yl]amino]phenyl]-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl]-2,2-difluoro-propan-1-ol
CAS Number
PubChem CID
UNII
KEGG
ChEMBL
Chemical and physical data
FormulaC27H31F5N4O
Molar mass522.564 g·mol−1
3D model (JSmol)
  • C[C@@H]1CC2=C([C@H](N1CC(CO)(F)F)C3=C(C=C(C=C3F)NC4CN(C4)CCCF)F)NC5=CC=CC=C25
  • InChI=InChI=1S/C27H31F5N4O/c1-16-9-20-19-5-2-3-6-23(19)34-25(20)26(36(16)14-27(31,32)15-37)24-21(29)10-17(11-22(24)30)33-18-12-35(13-18)8-4-7-28/h2-3,5-6,10-11,16,18,26,33-34,37H,4,7-9,12-15H2,1H3/t16-,26-/m1/s1
  • Key:GQCXHIKRWBIQMD-AKJBCIBTSA-N

Giredestrant is an investigational oral selective estrogen receptor degrader (SERD) being developed for the treatment of estrogen receptor-positive (ER+) breast cancer.[1][2] It is a potent, nonsteroidal compound that antagonizes estrogen effects by competitively binding to both wild-type and mutant estrogen receptors with nanomolar potency.[1][3] Giredestrant works by inducing an inactive conformation of the estrogen receptor ligand-binding domain and promoting proteasome-mediated degradation of the receptor protein.[1][4][5]

Research

In clinical trials, giredestrant has been evaluated in patients with ER+ breast cancer, including those with ESR1 mutations, both as a single agent and in combination with other therapies.[2][6] Its orally bioavailable.[3][4]

References

  1. ^ a b c "Giredestrant (GDC-9545)". NCI Formulatry. U.S. National Cancer Institute.
  2. ^ a b Malhi V, Agarwal P, Gates MR, Liu L, Wang J, De Bruyn T, et al. (December 2023). "Optimizing Early-stage Clinical Pharmacology Evaluation to Accelerate Clinical Development of Giredestrant in Advanced Breast Cancer". Cancer Research Communications. 3 (12): 2551–2559. doi:10.1158/2767-9764.CRC-23-0324. PMC 10722959. PMID 38019116.
  3. ^ a b "A clinical study to compare giredestrant with fulvestrant, both combined with a targeted therapy (CDK4/6 inhibitor) in people with ER‑positive, HER2-negative breast cancer that has come back after adjuvant hormone therapy". Roche.
  4. ^ a b Jhaveri KL, Bellet M, Turner NC, Loi S, Bardia A, Boni V, et al. (February 2024). "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. 30 (4): 754–766. doi:10.1158/1078-0432.CCR-23-1796. PMC 10870118. PMID 37921755.
  5. ^ Liang J, Zbieg JR, Blake RA, Chang JH, Daly S, DiPasquale AG, et al. (August 2021). "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. 64 (16): 11841–11856. doi:10.1021/acs.jmedchem.1c00847. PMID 34251202.
  6. ^ Lawrence L (25 July 2024). "Giredestrant Bests Anastrozole in ER+, HER2- Early Breast Cancer".

Further reading

Stub icon

This pharmacology-related article is a stub. You can help Wikipedia by expanding it.