BRD0705

SKU: orb1309904

Description

BRD0705 is a potent, orally bioavailable small molecule inhibitor with significant selectivity for GSK3α over GSK3β. It is a valuable research tool for investigating the distinct roles of GSK3 paralogs in cellular signaling, proliferation, and in vivo models of disease.

Research Area

Signal Transduction, Stem Cell & Developmental Biology

Key Properties

• CAS Number: 2056261-41-5
• MW: 321.42
• Purity: 99.59% (May vary between batches)
• Formula: C₂₀H₂₃N₃O
• SMILES: CC[C@@]1(C2=CNNC2=NC2=C1C(=O)CC(C)(C)C2)c1ccccc1
• Target: GSK-3
• Solubility: DMSO:300 mg/mL (933.36 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:5 mg/mL (15.56 mM)

Bioactivity

• Target IC50:
  GSK-3α:4.8 μM (Kd)|GSK-3α:66 nM|GSK-3β (WT):515 nM
• In Vivo:
  In AML mouse models, BRD0705 (30 mg/kg; oral gavage; twice daily; NSG mice) treatment impairs leukemia initiation and prolongs survival.
• In Vitro:
  BRD0705 displays excellent selectivity in a penal of 311 kinases, the CDK family of kinases (CDK2, 3 and 5) are next most potently inhibits at values of 6.87 μM, 9.74 μM and 9.20 μM (87-fold, 123-fold and 116-fold selectivity relative to GSK3α). BRD0705 (10-40 μM; 2-24 hours; U937 cells) treatment impairs GSK3α Tyr279 phosphorylation in a time-and concentration-dependent manner without affecting GSK3β Tyr216 phosphorylation. BRD0705 impairs AML colony formation in all six tested cell lines, MOLM13, TF-1, U937, MV4-11, HL-60, and NB4, in a concentration-dependent manner, as opposed to BRD3731 which impairs colony formation in TF-1 while increasing colony-forming ability in the MV4-11 cell line.
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Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

β-catenin, survival, GSK-3β(WT), GSK-3α, GSK3α, GSK-3, GSK3, Glycogen synthase kinase-3, Glycogen synthase kinase 3, leukemia, Inhibitor, oral, inhibit, kinase, myeloid, BRD 0705, BRD0705, BRD-0705, bioavailability, Acute

Compound Identifiers

PubChem CID

136980453