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CX-6258 HCl
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。
CX-6258 HCl图片
CAS NO:1353859-00-3
规格:≥98%
包装与价格：
包装价格(元)
5mg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)498.40
FormulaC26H24ClN3O3.HCl
CAS No.1353859-00-3
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 89 mg/mL (178.6 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Other info

Chemical Name: (3E)-5-Chloro-3-[[5-[3-[(hexahydro-4-methyl-1H-1,4-diazepin-1-yl)carbonyl]phenyl]-2-furanyl]methylene]-1,3-dihydro-2H-indol-2-one hydrochloride

InChi Key: YYIMMVXTWBIEAG-YHLMHSEJSA-N

InChi Code: InChI=1S/C26H24ClN3O3.ClH/c1-29-10-3-11-30(13-12-29)26(32)18-5-2-4-17(14-18)24-9-7-20(33-24)16-22-21-15-19(27)6-8-23(21)28-25(22)31;/h2,4-9,14-16H,3,10-13H2,1H3,(H,28,31);1H/b22-16+;

SMILES Code: O=C1NC2=C(C=C(Cl)C=C2)/C1=C\C3=CC=C(C4=CC=CC(C(N5CCN(C)CCC5)=O)=C4)O3.[H]Cl

SynonymsCX 6258 HCl; CX6258 HCl; CX-6258 HCl; CX 6258 Hydrochloride; CX6258 Hydrochloride; CX-6258 Hydrochloride;
实验参考方法
In Vitro

In vitro activity: CX-6258 shows antiproliferative activity against a panel of human cancer cell lines with IC50 of 0.02-3.7 μM, mostly sensitive to acute leukemia cell lines. Combinations of CX-6258 with doxorubicin (10:1 molar ratio) and CX-6258 with paclitaxel (100:1 molar ratio) produces synergistic cell killing with combination index (CI50) values equal to 0.4 and 0.56, respectively. CX-6258 causes dose dependent inhibition of the phosphorylation of two pro-survival proteins, Bad and 4E-BP1, at the Pim kinase specific sites S112 and S65 and T37/46, respectively.

Kinase Assay: Pim-1 and Pim-2 inhibitions are measured in radiometric assays using human recombinant Pim-1 at [ATP] = 30 μM (substrate RSRHSSYPAGT) and human recombinant Pim-2 at [ATP] = 5 μM (substrate RSRHSSYPAGT). The radiometric assay for Pim-3 uses RSRHSSYPAGT as a substrate in the presence of [ATP] = 155 μM.

Cell Assay: CX-6258 showed robust antiproliferative potencies against all cell lines tested derived from human solid tumors and hematological malignancies. In mechanistic cellular assays with MV-4-11 human AML cells, (13) caused dose-dependent inhibition of the phosphorylation of 2 pro-survival proteins, Bad and 4E-BP1, at the Pim kinase specific sites S112 and S65 and T37/46, respectively[1]. Pim-1 inhibition using the small molecule inhibitor CX-6258 (12 mM, 3 h) diminishes endogenous NKX3.1 steady state levels in 22RV1 and LNCaP cells. CX-6258 treatment (12 mM, 3 h) treatment diminished steady-state levels of ectopic NKX3.1 in PC3 cells. CX-6258 treatment resulted in a significant reduction in NKX3.1 half-life. While ectopically expressed NKX3.1 in control cells had a half-life of _90 min, Pim-1 inhibition reduced the half-life to _52 min

In VivoCX-6258 exhibits dose dependent efficacy in suppressing tumor growth in mice carrying MV-4-11 xenografts, with a 50 mg/kg dose producing 45% tumor growth inhibition (TGI) and a 100 mg/kg dose producing 75% TGI
Animal modelMice carrying MV-4-11 xenografts
Formulation & Dosage50 and 100 mg/kg/day; p.o.
References

ACS Med. Chem. Lett., 2012, 3 (2), pp 135–139.