[CAS NO. 1936421-41-8] GNE-049
PRODUCTS SPECIFICATIONS [1936421-41-8]
DESCRIPTION [1936421-41-8]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 510.58 |
| Molecular Formula | C27H32F2N6O2 |
| SMILES | CC(N1CCC(N(C2CCOCC2)N=C3N4CCCC5=C4C=C(C(F)F)C(C6=CN(C)N=C6)=C5)=C3C1)=O |
2 Publications Citing Use of MCE
Summary
GNE-049 is a highly potent and selective CBP inhibitor with an IC 50 of 1.1 nM in TR-FRET assay. GNE-049 also inhibits BRET and BRD4(1) with IC 50 s of 12 nM and 4200 nM, respectively [1] .
IC50 & Target
IC50: 1.1 nM (CBP), 12 nM (BRET), 4200 nM (BRD4(1)) [1]
In Vitro
GNE-049 is selected for further profiling as it has the best balance of liver microsomes (LM) stability, selectivity, and cellular potency GNE-049 has excellent potency in the BRET cellular assay and, in an orthogonal measure of the target engagement, GNE-049 is shown to inhibit the expression of MYC (MV4-11 cell line) with an EC 50 of 14 nM [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
GNE-049 demonstrates acceptable PK in mouse, rat, dog, and monkey. Determination of potency versus a selection of bromodomains revealed that GNE-049 is selective for CBP/P300 and, importantly, quite selective (3820-fold) over BRD4(1). GNE-049 is further evaluated in a rat single dose (30-250 mg/kg QD) toxicokinetic study. Adverse central nervous system (CNS)-related signs (e.g., marked hyperactivity and vocalization) are observed in several of the rats at the 250 mg/kg dose level. Furthermore, at the 250 mg/kg dose level, the ratio of the unbound drug concentration in brain to unbound drug concentration in plasma (K p,uu ) 3 h post dose is determined to be 0.43, indicating that GNE-049 is penetrating into the CNS and potentially resulting in the observed toxicity [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
-20°C, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
Solvent & Solubility
DMSO : 100 mg/mL ( 195.86 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.9586 mL | 9.7928 mL | 19.5856 mL |
| 5 mM | 0.3917 mL | 1.9586 mL | 3.9171 mL |
| 10 mM | 0.1959 mL | 0.9793 mL | 1.9586 mL |
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Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 2.5 mg/mL (4.90 mM); Clear solution
