Giredestrant (GDC-9545) is a non-steroidal estrogen receptor (ER) ligand, orally bioavailable, selective ER antagonist. Giredestrant can compete with estradiol (Estradiol) for binding within the ER ligand-binding domain and induce conformational changes. Giredestrant has anti-tumor effects.

Physicochemical Properties

Molecular Formula	C₂₇H₃₁F₅N₄O
Molecular Weight	522.55
Exact Mass	522.24
Elemental Analysis	C, 62.06; H, 5.98; F, 18.18; N, 10.72; O, 3.06
CAS #	1953133-47-5
Related CAS #	Giredestrant tartrate;2407529-33-1
PubChem CID	121410806
Appearance	Light yellow to yellow solid powder
Density	1.333±0.06 g/cm3(Predicted)
Boiling Point	618.8±55.0 °C(Predicted)
LogP	4.8
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	9
Rotatable Bond Count	9
Heavy Atom Count	37
Complexity	746
Defined Atom Stereocenter Count	2
SMILES	FC(C([H])([H])O[H])(C([H])([H])N1[C@]([H])(C([H])([H])[H])C([H])([H])C2C3=C([H])C([H])=C([H])C([H])=C3N([H])C=2[C@@]1([H])C1C(=C([H])C(=C([H])C=1F)N([H])C1([H])C([H])([H])N(C([H])([H])C([H])([H])C([H])([H])F)C1([H])[H])F)F
InChi Key	GQCXHIKRWBIQMD-AKJBCIBTSA-N
InChi Code	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
Chemical Name	3-((1R,3R)-1-(2,6-difluoro-4-((1-(3-fluoropropyl)azetidin-3-yl)amino)phenyl)-3-methyl-1,3,4,9-tetrahydro-2H-pyrido[3,4-b]indol-2-yl)-2,2-difluoropropan-1-ol
Synonyms	GDC-9545 RG6171GDC9545 RG-6171GDC 9545 RG 6171Giredestrant
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	Giredestrant (GDC-9545) is a new ER antagonist with favorable preclinical and mechanistic DMPK characteristics. Giredestrant's high ER binding capacity, total suppression of ER signaling, and enhanced DMPK profile could all contribute to its great in vivo efficacy [1].
References	[1]. Abstract P5-04-07: GDC-9545: A novel ER antagonist and clinical candidate that combines desirable mechanistic and pre-clinical DMPK attributes.
Additional Infomation	Giredestrant is an orally available selective estrogen receptor degrader/downregulator (SERD), with potential antineoplastic activity. Upon oral administration, giredestrant specifically targets and binds to the estrogen receptor (ER) and induces a conformational change that promotes ER degradation. This prevents ER-mediated signaling and inhibits both the growth and survival of ER-expressing cancer cells.

Solubility Data

Solubility (In Vitro)

DMSO : ~50 mg/mL (~95.68 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (4.78 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 (4.78 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (4.78 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.9137 mL	9.5685 mL	19.1369 mL
	5 mM	0.3827 mL	1.9137 mL	3.8274 mL
	10 mM	0.1914 mL	0.9568 mL	1.9137 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.