Size | Price | Stock | Qty |
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5mg |
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10mg |
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25mg |
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50mg |
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100mg |
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250mg |
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Other Sizes |
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Purity: ≥98%
GNE-272 is a novel, potent and selective in vivo chemical probe for and inhibitor of the CBP/EP300 bromodomains with IC50 values of 0.02, 0.03 and 13 μM for CBP, EP300 and BRD4, respectively. The single bromodomain of the closely related transcriptional regulators CBP/EP300 is a target of much recent interest in cancer and immune system regulation. A co-crystal structure of a ligand-efficient screening hit and the CBP bromodomain guided initial design targeting the LPF shelf, ZA loop, and acetylated lysine binding regions. Structure-activity relationship studies allowed us to identify a more potent analogue. Optimization of permeability and microsomal stability and subsequent improvement of mouse hepatocyte stability afforded 59 (GNE-272, TR-FRET IC50 = 0.02 μM, BRET IC50 = 0.41 μM, BRD4(1) IC50 = 13 μM) that retained the best balance of cell potency, selectivity, and in vivo PK. GNE-272 showed a marked antiproliferative effect in hematologic cancer cell lines and modulates MYC expression in vivo that corresponds with antitumor activity in an AML tumor model.
ln Vitro |
GNE-272 is 650 times more selective than BRD4 and has good selectivity for CBP/EP300. Tested at 10 μM across 42 receptor and 35 kinase off-target screens, GNE-272 did not inhibit any target by more than thirty percent. Furthermore, GNE-272 does not inhibit several cytochrome P450s (3A4, 1A2, 2C9, 2C19, 2D6) at concentrations greater than 10 μM. The efficacy of this chemical in BRET cell tests is good. GNE-272 was found to decrease MYC10 (MV4-11 cell line) expression with an EC50 of 0.91 μM in an orthogonal assessment of target engagement, and there was a strong connection between BRET and MYC cell assays [1].
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ln Vivo |
GNE-272 had a good oral bioavailability of 26 μM when given at a dose of 100 mg/kg in mice PK tests, but showed limited clearance following an intravenous injection of 1 mg/kg. not in conjunction with Cmax. GNE-272 influences MYC expression in vivo and exhibits strong anti-proliferative effects in hematological cancer cell lines, both of which are indicative of anti-tumor efficacy in AML tumor models [1].
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References |
[1]. Crawford TD, et al. Discovery of a Potent and Selective in Vivo Probe (GNE-272) for the Bromodomains of CBP/EP300. J Med Chem. 2016 Dec 8;59(23):10549-10563
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Molecular Formula |
C22H25FN6O2
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Molecular Weight |
424.471307516098
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CAS # |
1936428-93-1
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SMILES |
CC(N1CCC2=C(C(NC3=C(F)C=C(C4=CN(C)N=C4)C=C3)=NN2[C@H]5CCOC5)C1)=O
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InChi Key |
NKOJNOBJGYTLLZ-KRWDZBQOSA-N
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InChi Code |
InChI=1S/C22H25FN6O2/c1-14(30)28-7-5-21-18(12-28)22(26-29(21)17-6-8-31-13-17)25-20-4-3-15(9-19(20)23)16-10-24-27(2)11-16/h3-4,9-11,17H,5-8,12-13H2,1-2H3,(H,25,26)/t17-/m0/s1
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Chemical Name |
(S)-1-(3-((2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)phenyl)amino)-1-(tetrahydrofuran-3-yl)-1,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl)ethan-1-one
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Synonyms |
GNE-272; GNE 272; GNE272.
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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)
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Solubility (In Vitro) |
DMSO : ~100 mg/mL (~235.59 mM)
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Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.3559 mL | 11.7794 mL | 23.5588 mL | |
5 mM | 0.4712 mL | 2.3559 mL | 4.7118 mL | |
10 mM | 0.2356 mL | 1.1779 mL | 2.3559 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.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.