Rintodestrant

Rintodestrant
Clinical data
Other names	G1T48
Identifiers
	IUPAC name (E)-3-[4-[2-(4-fluoro-2,6-dimethyl-benzoyl)-6-hydroxy-benzothiophen-3-yl]oxyphenyl]prop-2-enoic acid;
CAS Number	2088518-51-6;
PubChem CID	129205616;
ChemSpider	76743881;
UNII	W3Y784Y0ES;
KEGG	D11736;
ChEMBL	ChEMBL4059888;
Chemical and physical data
Formula	C26H19FO5S
Molar mass	462.49 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC1=CC(=CC(=C1C(=O)C2=C(C3=C(S2)C=C(C=C3)O)OC4=CC=C(C=C4)/C=C/C(=O)O)C)F;
	InChI InChI=InChI=1S/C26H19FO5S/c1-14-11-17(27)12-15(2)23(14)24(31)26-25(20-9-6-18(28)13-21(20)33-26)32-19-7-3-16(4-8-19)5-10-22(29)30/h3-13,28H,1-2H3,(H,29,30)/b10-5+; Key:KOAITBOFZOEDOC-BJMVGYQFSA-N;

Rintodestrant (G1T48) is an orally bioavailable selective estrogen receptor degrader (SERD) discovered in Greg Thatcher's lab at UIC^[1] and developed by G1 Therapeutics for the treatment of estrogen receptor-positive (ER+) breast cancer^[2]. Structurally inspired by the 6-OH-benzothiophene scaffold used in arzoxifene and raloxifene, rintodestrant selectively binds to the estrogen receptor and inhibits ER signaling, demonstrating efficacy in endocrine-resistant tumors.^[3]

A phase I clinical trial evaluated rintodestrant as monotherapy and in combination with the CDK4/6 inhibitor palbociclib in patients with ER+/HER2- advanced breast cancer.^[4]

References

↑ Xiong R, Zhao J, Gutgesell LM, Wang Y, Lee S, Karumudi B, et al. (February 2017). "Novel Selective Estrogen Receptor Downregulators (SERDs) Developed against Treatment-Resistant Breast Cancer". Journal of Medicinal Chemistry. 60 (4): 1325–1342. doi:10.1021/acs.jmedchem.6b01355. PMID 28117994.
↑ Andreano KJ, Wardell SE, Baker JG, Desautels TK, Baldi R, Chao CA, et al. (April 2020). "G1T48, an oral selective estrogen receptor degrader, and the CDK4/6 inhibitor lerociclib inhibit tumor growth in animal models of endocrine-resistant breast cancer". Breast Cancer Research and Treatment. 180 (3): 635–646. doi:10.1007/s10549-020-05575-9. PMC 7103015. PMID 32130619.
↑ Gheysen M, Punie K, Wildiers H, Neven P (November 2024). "Oral SERDs changing the scenery in hormone receptor positive breast cancer, a comprehensive review". Cancer Treatment Reviews. 130 102825. doi:10.1016/j.ctrv.2024.102825. PMID 39293125.
↑ Clinical trial number NCT03455270 for "G1T48, an Oral SERD, Alone and in Combination With Palbociclib in ER-Positive, HER2-Negative Advanced Breast Cancer" at ClinicalTrials.gov

[1] Xiong R, Zhao J, Gutgesell LM, Wang Y, Lee S, Karumudi B, et al. (February 2017). "Novel Selective Estrogen Receptor Downregulators (SERDs) Developed against Treatment-Resistant Breast Cancer". Journal of Medicinal Chemistry. 60 (4): 1325–1342. doi:10.1021/acs.jmedchem.6b01355. PMID 28117994.

[2] Andreano KJ, Wardell SE, Baker JG, Desautels TK, Baldi R, Chao CA, et al. (April 2020). "G1T48, an oral selective estrogen receptor degrader, and the CDK4/6 inhibitor lerociclib inhibit tumor growth in animal models of endocrine-resistant breast cancer". Breast Cancer Research and Treatment. 180 (3): 635–646. doi:10.1007/s10549-020-05575-9. PMC 7103015. PMID 32130619.

[Gheysen_2024-3] Gheysen M, Punie K, Wildiers H, Neven P (November 2024). "Oral SERDs changing the scenery in hormone receptor positive breast cancer, a comprehensive review". Cancer Treatment Reviews. 130 102825. doi:10.1016/j.ctrv.2024.102825. PMID 39293125.

[4] Clinical trial number NCT03455270 for "G1T48, an Oral SERD, Alone and in Combination With Palbociclib in ER-Positive, HER2-Negative Advanced Breast Cancer" at ClinicalTrials.gov

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