product name UNC-2025 HCl
Description: UNC-2025 HCl is a novel, potent and orally bioavailable dual MER/FLT3 inhibitor 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.
References: J Med Chem. 2014 Aug 28;57(16):7031-41; Mol Cancer Ther. 2015 Sep;14(9):2014-22.
513.12
Formula
C28H41ClN6O
CAS No.
1429881-91-3 (free base)
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 25 mg/mL (48.7 mM)
Water: 100 mg/mL (194.9 mM)
Ethanol: 8 mg/mL (15.6 mM)
Solubility (In vivo)
Synonyms
UNC-2025 hydrochloride
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19421151
| In Vitro |
In vitro activity: 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. Kinase Assay: Cell Assay: |
|---|---|
| In Vivo | In 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 model | NOD/SCID/gamma mice bearing 697 acute leukemia tumor |
| Formulation & Dosage | Formulated in 0.5% (w/v) NaCMC with 0.1% (v/v) Tween-80 in water; 3 mg/kg; Oral gavage |
| References | J Med Chem. 2014 Aug 28;57(16):7031-41; Mol Cancer Ther. 2015 Sep;14(9):2014-22. |
