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UNC-2025
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
UNC-2025图片
CAS NO:1429881-91-3
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW)476.66
FormulaC28H40N6O
CAS No.1429881-91-3
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: > 5 mg/mL
Water: < 4.9 mg/mL
Ethanol: N/A
SMILES CodeO[C@H]1CC[C@H](N2C=C(C3=CC=C(CN4CCN(C)CC4)C=C3)C5=CN=C(NCCCC)N=C52)CC1
SynonymsUNC2025, UNC 2025, UNC2025,

Chemical Name: (1r,4r)-4-(2-(butylamino)-5-(4-((4-methylpiperazin-1-yl)methyl)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclohexanol

Exact Mass: 476.32636

实验参考方法
In Vitro

In vitro activity: UNC-2025 is a novel, potent and orally bioavailable dual inhibitor of MER/FLT3 with IC50 of 0.74 nM and 0.8 nM, respectively, it displayed about 20-fold selectivity over Axl and Tyro3. UNC-2025 is capable of inhibiting Mer phosphorylation in vivo. Kinome profiling versus more than 300 kinases in vitro and cellular selectivity assessments demonstrate that UNC-2025 has similar subnanomolar activity against Flt3, an additional important target in acute myelogenous leukemia (AML), with pharmacologically useful selectivity versus other kinases examined.


Kinase Assay: UNC2025 hydrochloride is a potent and orally bioavailable Mer/Flt3 dual inhibitor with IC50 of 0.8/0.74 nM for Mer/Flt3. UNC2025 was capable of inhibiting Mer phosphorylation in vivo, following oral dosing as demonstrated by pharmaco-dynamic (PD) studies examining phospho-Mer in leukemic blasts from mouse bone marrow. Kinome profiling versus more than 300 kinases in vitro and cellular selectivity assessments demonstrate that 11 has similar subnanomolar activity against Flt3, an additional important target in acute myelogenous leukemia (AML), with pharmacologically useful selectivity versus other kinases examined.


Cell Assay: In 697 B-ALL cells, UNC-2025 potently inhibits Mer phosphorylation with IC50 of 2.7 nM. In A549 NSCLC and Molm-14 AML cell lines, UNC-2025 causes significant inhibition of colony formation dependent on Mer8 and Flt3. In H2228 and H1299 cell lines, UNC-2025 inhibits MERTK oncogenic signaling downstream, such as basal and stimulated pAKT and pERK1/2. In four NSCLC cell lines, UNC-2025 also induces apoptotic cell death, and decreases colony formation.

In VivoIn mice bearing 697 acute leukemia tumors, UNC-2025 (3 mg/kg, p.o.) shows good solubility and DMPK properties, and results in effective target inhibition. In mice bearing H2228 or A549 tumors, UNC-2025 (50 mg/kg, p.o.) inhibits tumor growth
Animal modelNOD/SCID/gamma mice bearing 697 acute leukemia tumor
Formulation & DosageFormulated in 0.5% (w/v) NaCMC with 0.1% (v/v) Tween-80 in water; 3 mg/kg; Oral gavage
ReferencesJ Med Chem. 2014 Aug 28;57(16):7031-41; Mol Cancer Ther. 2015 Sep;14(9):2014-22.