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Description
Overview
A cell-permeable furopyrimidine that acts as a potent, ATP-binding site-targeting, Ack1-selective inhibitor (IC50 = 22 nM) and effectively prevents receptor-mediated Ack1 activation (by >90% in MEF & LAPC4 cultures; 16 h 800 nM), while exhibiting much reduced potency against Lyn, Lck, Abl1 and BTK (IC50 ≥346.7 nM) and no inhibitory activity toward 25 other kinases. Shown to completely inhibit EGF-induced, but not androgen DHT- (dihydrotestosterone) stimulated, AR transcription activity in serum- and androgen-deprived prostate cancer LAPC4 cutlures. Effectively inhibits androgen-independent LNCaP prostate cancer growth both in vitro (by 60%; 72 h 8 µM) and in castrated mice in vivo (4 mg/kg/96 h injections on day 7/11/15/19/23/27 post tumor transplant).
Mahajan, K., et al. 2012. J. Biol. Chem.287, 22112. Mahajan, K., et al. 2012. Am. J. Pathol.180, 1386. Mahajan, K., et al. 2010. Prostate70, 1274. DiMauro, E.F., et al. 2007. Bioorg. Med. Chem. Lett.17, 2305.
Product Information
CAS number
873305-35-2
Form
Yellow solid
Hill Formula
C₂₃H₂₁N₃O₂
Chemical formula
C₂₃H₂₁N₃O₂
Reversible
Y
Applications
Biological Information
Primary Target
Ack1
Primary Target IC<sub>50</sub>
22 nM for Ack1
Secondary target
Lck, Lyn
Purity
≥98% by Chiral HPLC Enantiomeric excess (ee): 98.29% (based on the ee of (S)-(+)-Tetrahydrofurfurylamine, as determined using Chiral HPLC column)
Physicochemical Information
Cell permeable
Y
Dimensions
Materials Information
Toxicological Information
Safety Information according to GHS
Safety Information
Product Usage Statements
Storage and Shipping Information
Ship Code
Ambient Temperature Only
Toxicity
Standard Handling
Storage
-20°C
Protect from Light
Protect from light
Avoid freeze/thaw
Avoid freeze/thaw
Do not freeze
Ok to freeze
Special Instructions
Following reconstitution, aliquot and freeze (-20°C. Stock solutions are stable for up to 6 months at -20°C.
Mahajan, K., et al. 2012. J. Biol. Chem.287, 22112. Mahajan, K., et al. 2012. Am. J. Pathol.180, 1386. Mahajan, K., et al. 2010. Prostate70, 1274. DiMauro, E.F., et al. 2007. Bioorg. Med. Chem. Lett.17, 2305.
Data Sheet
Note that this data sheet is not lot-specific and is representative of the current specifications for this product. Please consult the vial label and the certificate of analysis for information on specific lots. Also note that shipping conditions may differ from storage conditions.
A cell-permeable furopyrimidine that acts as a potent, ATP-binding site-targeting, Ack1-selective inhibitor (IC50 = 22 nM) and effectively prevents receptor-mediated Ack1 activation (>90% of 10 ng/mL EGF-induced Ack1 Tyr284 phosphorylation in MEF and LAPC4 cells with 16 h 800 nM inhibitor pretreatment), while exhibiting much reduced potency against Lyn, Lck, Abl1 and BTK (IC50 = 346.7, 432.3, 705.9 and 871.7 nM, respectively) and no inhibitory activity toward 25 other kinases. Shown to completely inhibit EGF-induced, but not androgen DHT (dihydrotestosterone)-stimulated, AR (androgen receptor) transcription activity in serum- and androgen-deprived prostate cancer LAPC4 cutlures by preventing Ack1 activation-dependent AR Tyr267 phosphorylation. Effectively inhibits androgen-independent prostate cancer growth both in vitro (by 60% in 72 h 8 µM-treated LNCaP and 108 h 4 µM-treated LAPC4 cultures) and in castrated mice in vivo (18% and 51% of control tumor size on day 27, respectively, of irradiated and non-irradiated active Ack1-expressing LNCaP; Six 4 mg/kg/96 h injections on day 7/11/15/19/23/27 post tumor transplant).
Form
Yellow solid
Intert gas (Yes/No)
Packaged under inert gas
CAS number
873305-35-2
Chemical formula
C₂₃H₂₁N₃O₂
Purity
≥98% by Chiral HPLC Enantiomeric excess (ee): 98.29% (based on the ee of (S)-(+)-Tetrahydrofurfurylamine, as determined using Chiral HPLC column)
Solubility
DMSO (100 mg/ml)
Storage
-20°C
Protect from light
Avoid freeze/thaw
Do Not Freeze
Ok to freeze
Special Instructions
Following reconstitution, aliquot and freeze (-20°C. Stock solutions are stable for up to 6 months at -20°C.
Toxicity
Standard Handling
References
Mahajan, K., et al. 2012. J. Biol. Chem.287, 22112. Mahajan, K., et al. 2012. Am. J. Pathol.180, 1386. Mahajan, K., et al. 2010. Prostate70, 1274. DiMauro, E.F., et al. 2007. Bioorg. Med. Chem. Lett.17, 2305.
