BRD0705

Catalog No.S9638 Batch:S963801

Technical Data

Formula	C₂₀H₂₃N₃O
Molecular Weight	321.42	CAS No.	2056261-41-5
Solubility (25°C)*	In vitro	DMSO	64 mg/mL (199.11 mM)
		Ethanol	64 mg/mL (199.11 mM)
		Water	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description

BRD0705 is a potent, paralog selective and orally active inhibitor of GSK3α (Glycogen synthase kinase 3α) with IC50 of 66 nM and Kd of 4.8 μM. BRD0705 also inhibits GSK3β with IC50 of 515 nM. BRD0705 can be used for acute myeloid leukemia (AML).

Targets

GSK3α ^[1] (Cell-free assay)	GSK3β ^[1] (Cell-free assay)	GSK3α ^[1] (Cell-free assay)
66 nM	515 nM(Kd)	4.8 μM(Kd)

In vitro

BRD0705 inhibits kinase function and does not stabilize β-catenin, mitigating potential neoplastic concerns. BRD0705 induces myeloid differentiation and impairs colony formation in AML cells while no effect is observed on normal hematopoietic cells.^[1]

In vivo

BRD0705 impairs leukemia initiation and prolongs survival in AML mouse models.^[1]

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines HEK 293T, HL-60, U937, TF-1, NB-4, MV4–11, MOLM-13, Mononuclear cells Concentrations 20 μM Incubation Time 24 hours Method After 24 hours of treatment with DMSO or BRD0705 at 20 μM, 30,000 to 50,000 cells are washed in PBS/2%FBS and then cytospun onto poly-L-Lysine coated slides (EMS). Cells are fixed in 4% paraformaldehyde (EMS) for 20 minutes, permeabilized in 0.2% Triton X-100 (RPI) for 30 minutes at 4°C, blocked in 1% BSA/0.05% triton for 1 hour at room temperature and then incubated for 1 hour at room temperature with primary anti-β-catenin (1/500) and then secondary antibody. Three 5 minute washes are performed after each antibody incubation. Slides are mounted with Prolong (R) Gold Antifade with DAPI and imaged with Yokogawa Spinning Disk Confocal / TIRF system. Representative images of three independent experiments are analyzed with Image-J software.
Animal Study:^{^[1]}	Animal Models 8-week-old male NSG mice Dosages 15 mg/kg, 30 mg/kg Administration Oral gavage

Cell Assay:^{^[1]}

Cell lines
HEK 293T, HL-60, U937, TF-1, NB-4, MV4–11, MOLM-13, Mononuclear cells
Concentrations
20 μM
Incubation Time
24 hours
Method
After 24 hours of treatment with DMSO or BRD0705 at 20 μM, 30,000 to 50,000 cells are washed in PBS/2%FBS and then cytospun onto poly-L-Lysine coated slides (EMS). Cells are fixed in 4% paraformaldehyde (EMS) for 20 minutes, permeabilized in 0.2% Triton X-100 (RPI) for 30 minutes at 4°C, blocked in 1% BSA/0.05% triton for 1 hour at room temperature and then incubated for 1 hour at room temperature with primary anti-β-catenin (1/500) and then secondary antibody. Three 5 minute washes are performed after each antibody incubation. Slides are mounted with Prolong (R) Gold Antifade with DAPI and imaged with Yokogawa Spinning Disk Confocal / TIRF system. Representative images of three independent experiments are analyzed with Image-J software.

Animal Study:^{^[1]}

Animal Models
8-week-old male NSG mice
Dosages
15 mg/kg, 30 mg/kg
Administration
Oral gavage

References

[1] Florence F Wagner, et al. Sci Transl Med. 2018 Mar 7;10(431):eaam8460.

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SHIPPING AND STORAGE
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