AZD-0284 is a novel, potent, selective, inverse agonist of the nuclear receptor RORγ. It is in development for the treatment of plaque psoriasis vulgaris and respiratory tract disorders.

Physicochemical Properties

Molecular Formula	C21H18F6N2O5S
Molecular Weight	524.433445453644
Exact Mass	524.084
CAS #	2101291-07-8
PubChem CID	129205086
Appearance	White to off-white solid powder
LogP	2.3
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	11
Rotatable Bond Count	4
Heavy Atom Count	35
Complexity	910
Defined Atom Stereocenter Count	1
SMILES	S(C)(C1C=CC2=C(C=1)CN(C(C)=O)[C@H]2C(NC1C=CC(=CC=1)C(C(F)(F)F)(C(F)(F)F)O)=O)(=O)=O
InChi Key	QYYZXEPEVBXNNA-QGZVFWFLSA-N
InChi Code	InChI=1S/C21H18F6N2O5S/c1-11(30)29-10-12-9-15(35(2,33)34)7-8-16(12)17(29)18(31)28-14-5-3-13(4-6-14)19(32,20(22,23)24)21(25,26)27/h3-9,17,32H,10H2,1-2H3,(H,28,31)/t17-/m1/s1
Chemical Name	(R)-2-acetyl-N-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl)-5-(methylsulfonyl)isoindoline-1-carboxamide
Synonyms	AZD-0284; AZD 0284; AZD0284.
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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.
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	In human TH17 cells, AZD0284 (0.37 μM; 5 days) suppresses the synthesis of IL-17A [1]. TH17 polarization into pathogenic TH17/1 cells is decreased by AZD0284. Both the frequency of double-positive TH17/1 cells and single IL-17+ cells are decreased by AZD0284. AZD0284 decreases the expression of IL-17A, IL-17F, IL-22, and IL-23R on RNA [1][2].
References	[1]. The discovery of AZD0284, an inverse agonist of the nuclear receptor RORg. American Chemical Society, 2017 Drug Design and Delivery Symposium 26 October 2017. [2]. Pharmacokinetics, pharmacodynamics and safety of the inverse retinoic acid-related orphan receptor γ agonist AZD0284 [published online ahead of print, 2020 Feb 17]. Br J Clin Pharmacol. 2020;10.1111/bcp.14253.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~190.68 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 0.83 mg/mL (1.58 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 8.3 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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: ≥ 0.83 mg/mL (1.58 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 8.3 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: ≥ 0.83 mg/mL (1.58 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 8.3 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	1.9068 mL	9.5342 mL	19.0683 mL
	5 mM	0.3814 mL	1.9068 mL	3.8137 mL
	10 mM	0.1907 mL	0.9534 mL	1.9068 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.