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Onalespib lactate
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。
Onalespib lactate图片
CAS NO:1019889-35-0
规格:≥98%
包装与价格:
包装价格(元)
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


Name: Onalespib lactate
CAS#: 1019889-35-0 (lactate)
Chemical Formula: C27H37N3O6
Exact Mass:
Molecular Weight: 499.608
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Technical InformationSynonym: Onalespib lactate; AT-13387 lactate; ATI 13387; ATI-13387A; ATI-13387; ATI-13387AU; ATI13387.
Chemical Name: (2,4-dihydroxy-5-isopropylphenyl)(5-((4-methylpiperazin-1-yl)methyl)isoindolin-2-yl)methanone (S)-2-hydroxypropanoate
InChi Key: VYRWEWHOAMGLLW-WNQIDUERSA-N
InChi Code: InChI=1S/C24H31N3O3.C3H6O3/c1-16(2)20-11-21(23(29)12-22(20)28)24(30)27-14-18-5-4-17(10-19(18)15-27)13-26-8-6-25(3)7-9-26;1-2(4)3(5)6/h4-5,10-12,16,28-29H,6-9,13-15H2,1-3H3;2,4H,1H3,(H,5,6)/t;2-/m.0/s1
SMILES Code: C[C@H](O)C(O)=O.O=C(N1CC2=C(C=C(CN3CCN(C)CC3)C=C2)C1)C4=CC(C(C)C)=C(O)C=C4O
实验参考方法

In Vitro

In vitro activity: The Kd for AT13387 binding is 0.7 nM. This compares to a Kd of 6.7 nM for the binding of the ansamycin 17-AAG to the same site. The mean stoichio metry of binding for AT13387 is 1.03. The inhibition of a number of isolated kinases by AT13387 is also investigated including CDK 1, CDK 2, CDK4, FGFR3, PKB-b, JAK2, VEGFR2, PDGFRβ and Aurora B. None of the tested kinases are significantly inhibited at concentrations below 30 μM. AT13387 is a potent inhibitor of the proliferat ion and survival of many different cell lines (such as MES-SA cell line) from a variety of different tumor types. Across a panel of 30 tumor cell lines, AT13387 potently inhibits cell proliferation with GI50 values in the range 13-260 nM. AT13387 inhibits proliferation of the non-tumorigenic human prostate epithelial cell line PNT2 with a GI50 value of 480 NM.


Kinase Assay: Kd values for AT13387 binding to HSP90 are determined with a competition Isothermal Calorimetry (ITC) format. ITC experiments are performed on a Micro Cal VP-ITC at 25 °C in a buffer comprising 25 mM Tris, 100 mM NaCl, 1 mM MgCl2 and 1 mM Tris(2-carboxy- ethyl)phosphine at pH 7.4 in order to maintain the higher affinity.


Cell Assay: The human cell lines including A375, 22RV1, T474, DU1 45, LNCa P, MCF-7, DA-MB-468 are seeded into 96-well plates before the addition of AT13387 in 0.1% (v/v) DMSO. GI50 are determined using a 10-point dose response curve for three cell doubling times. After AT13387 incubation 10% (v/v), Alamar blueis added, and cells are incubated for a further 4 hours. Fluorescence is read.

In VivoWhen given on an intermittent basis, AT13387 could be tolerated at doses of up to 70 mg/kg twice weekly or 90 mg/kg once weekly. Body weight loss in mice does not exceed 20% before recovering in all cases except one, and loss is highest following the second dose. Tumor growth inhibition is similar in NCI-H1975 for both dosing regimens. The maintenance of antitumor effects with such a prolonged off-treatment period is consistent with the extended pharmacodynamic action of AT13387 observed for mutant EGFR and other biomarkers in vitro and in vivo and the extended retention of AT13387 in tumors.
Animal modelAthymic BALB /c mice
Formulation & DosageDissolved in 17.5% cyclodextrin; 80 mg/kg; i.p. injection
References

Cancer Sci. 2012 Mar;103(3):522-7.