AZD9567 is a novel, potent, oral bioactive, non-steroidal and selective glucocorticoid receptor modulator (SGRM) with an IC50 of 3.8 nM. AZD9567 has excellent in vivo efficacy when dosed orally in a rat model of joint inflammation. AZD9567 exhibits excellent efficacy in the streptococcal cell wall (SCW) reactivation model of joint inflammation. It is currently being evaluated in clinical trials comparing the efficacy and side effect markers with those of prednisolone.

Physicochemical Properties

Molecular Formula	C27H28F2N4O3
Molecular Weight	494.533033370972
Exact Mass	494.212
CAS #	1893415-00-3
PubChem CID	121248172
Appearance	Off-white to light brown solid powder
LogP	4.7
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	8
Heavy Atom Count	36
Complexity	871
Defined Atom Stereocenter Count	2
SMILES	FC(C)(C(N[C@@H]([C@H](C1C=CC=CC=1)OC1C=CC2=C(C=NN2C2C=CC(N(C)C=2)=O)C=1)C(C)C)=O)F
InChi Key	ZQFNDBISEYQVRR-LOSJGSFVSA-N
InChi Code	InChI=1S/C27H28F2N4O3/c1-17(2)24(31-26(35)27(3,28)29)25(18-8-6-5-7-9-18)36-21-11-12-22-19(14-21)15-30-33(22)20-10-13-23(34)32(4)16-20/h5-17,24-25H,1-4H3,(H,31,35)/t24-,25+/m0/s1
Chemical Name	2,2-difluoro-N-[(1R,2S)-3-methyl-1-[1-(1-methyl-6-oxopyridin-3-yl)indazol-5-yl]oxy-1-phenylbutan-2-yl]propanamide
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 Vivo	In a rat model of joint inflammation, mizakola treatment (15 mg/kg/day, orally delivered daily for 8 days) demonstrated great in vivo efficacy [1].
Animal Protocol	Animal/Disease Models: Female Lewis rats (175-200 g) antigen-induced joint inflammation model, sensitized by intra-articular injection of 5 μg SCW [1]. Doses: 15 mg/kg/day. Route of Administration: Daily oral administration for 8 days. Experimental Results: Inhibition of ankle joint swelling in rat SCW model.
References	[1]. Discovery of a Novel Oral Glucocorticoid Receptor Modulator (AZD9567) with Improved Side Effect Profile. J Med Chem. 2018 Mar 8;61(5):1785-1799.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~202.21 mM) H2O : ~0.67 mg/mL (~1.35 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.06 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 (5.06 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 (5.06 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	2.0221 mL	10.1106 mL	20.2212 mL
	5 mM	0.4044 mL	2.0221 mL	4.0442 mL
	10 mM	0.2022 mL	1.0111 mL	2.0221 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.