(Rac)-BRD0705 is a low-activity racemate of BRD0705, a potent, paraselective and orally bioactive GSK3α inhibitor (antagonist) with IC50 of 66 nM and Kd of 4.8 μM. BRD0705 is more selective (8-fold) for GSK3α than GSK3β (IC50 of 515 nM). BRD0705 is indicated for acute myeloid leukemia.

Physicochemical Properties

Molecular Formula	C20H23N3O
Molecular Weight	321.416124582291
Exact Mass	321.184
CAS #	1597440-03-3
Related CAS #	BRD0705;2056261-41-5;BRD5648;2056261-42-6
PubChem CID	136980454
Appearance	Light yellow to yellow solid powder
LogP	4.2
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	2
Heavy Atom Count	24
Complexity	561
Defined Atom Stereocenter Count	0
SMILES	O=C1CC(C)(C)CC2=C1C(C1C=CC=CC=1)(CC)C1C=NNC=1N2
InChi Key	NCKLQXXBRWCYMA-UHFFFAOYSA-N
InChi Code	InChI=1S/C20H23N3O/c1-4-20(13-8-6-5-7-9-13)14-12-21-23-18(14)22-15-10-19(2,3)11-16(24)17(15)20/h5-9,12H,4,10-11H2,1-3H3,(H2,21,22,23)
Chemical Name	4-ethyl-7,7-dimethyl-4-phenyl-1,6,8,9-tetrahydropyrazolo[3,4-b]quinolin-5-one
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

References

[1]. Exploiting an Asp-Glu "switch" in glycogen synthase kinase 3 to design paralog-selective inhibitors for use in acute myeloid leukemia. Sci Transl Med. 2018 Mar 7;10(431). pii: eaam8460. [2]. Uses of paralog-selective inhibitors of gsk3 kinases. US20160375006A1.

Solubility Data

Solubility (In Vitro)

DMSO : ~250 mg/mL (~777.80 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (6.47 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 20.8 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: ≥ 2.08 mg/mL (6.47 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 20.8 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: ≥ 2.08 mg/mL (6.47 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 20.8 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	3.1112 mL	15.5560 mL	31.1119 mL
	5 mM	0.6222 mL	3.1112 mL	6.2224 mL
	10 mM	0.3111 mL	1.5556 mL	3.1112 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.