Rintodestrant (G1T48) is an orally bioactive, nonsteroidal, selective estrogen receptor degrader. Rintodestrant (G1T48) is also an inhibitor (blocker/antagonist) of CDK4/6.

Physicochemical Properties

Molecular Formula	C26H19FO5S
Molecular Weight	462.489469766617
Exact Mass	462.093
CAS #	2088518-51-6
Related CAS #	2088518-51-6;
PubChem CID	129205616
Appearance	Solid powder
LogP	6.6
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	6
Heavy Atom Count	33
Complexity	724
Defined Atom Stereocenter Count	0
SMILES	S1C2C=C(C=CC=2C(=C1C(C1C(C)=CC(=CC=1C)F)=O)OC1C=CC(/C=C/C(=O)O)=CC=1)O
InChi Key	KOAITBOFZOEDOC-BJMVGYQFSA-N
InChi Code	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+
Chemical Name	(E)-3-[4-[[2-(4-fluoro-2,6-dimethylbenzoyl)-6-hydroxy-1-benzothiophen-3-yl]oxy]phenyl]prop-2-enoic acid
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	Rintodestrant (G1T48), like pure antiestrogen fulvestrant, is a strong and effective inhibitor of estrogen-mediated transcription and proliferation in ER-positive breast cancer cells[1]. Only ER-positive breast cancer cells are preferentially inhibited in their proliferation by rindodestrant (G1T48)[1].
ln Vivo	In endocrine-resistant breast cancer models, rimodestrant (G1T48, 30 or 100 mg/kg) blocks estrogen signaling[1].
Cell Assay	Cell Viability Assay[1] Cell Types: MCF7 cells. Tested Concentrations: 1 pM-1 μM. Incubation Duration: 18 h. Experimental Results: Downregulates the estrogen receptor in breast cancer cells. Dramatically inhibited estrogen-mediated growth of MCF7 cells demonstrating approximately threefold higher potency when compared to Fulvestrant. Does not impact apoptosis in MCF7 breast cancer cells.
Animal Protocol	Animal/Disease Models: MCF7 xenograft tumors[1] ]. Doses: 30 or 100 mg/kg. Route of Administration: PO daily for 28 days. Experimental Results: Demonstrated dose-dependent inhibition of TamR tumor growth.
References	[1]. 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 Res Treat. 2020 Apr;180(3):635-646.
Additional Infomation	Rintodestrant is an orally available selective estrogen receptor degrader/downregulator (SERD), with potential antineoplastic activity. Upon oral administration, rintodestrant specifically targets and binds to the estrogen receptor alpha (ERalpha; ERa; ESR1) and induces a conformational change that promotes ERalpha degradation and downregulation. This prevents ERalpha-mediated signaling and inhibits both the growth and survival of ERalpha-expressing cancer cells.

Solubility Data

Solubility (In Vitro)

DMSO : 50 mg/mL (108.11 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.41 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.41 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.1622 mL	10.8110 mL	21.6221 mL
	5 mM	0.4324 mL	2.1622 mL	4.3244 mL
	10 mM	0.2162 mL	1.0811 mL	2.1622 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.