I-CBP112

A p300 and CBP inhibitor

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1mg

￥1087.00

870.00

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5mg

￥3012.00

2410.00

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10mg

￥5350.00

4280.00

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50mg

￥19062.00

15250.00

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100mg

￥29675.00

23740.00

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Background

I-CBP112 is an inhibitor of p300 and CREB-binding protein (CBP) histone acetyltransferases.¹ It binds to the p300 and CBP bromodomains (K_ds = 167 and 151 nM, respectively) and is selective for p300 and CBP over BRD4, as well as a panel of 104 nuclear receptors and ion channels and a panel of 32 enzymes at 10 ?M. I-CBP112 displaces acetylated histones from CBP in a cell-free assay (IC₅₀ = 170 nM). It reduces colony formation and increases differentiation of primary murine leukemic blasts and delays disease initiation following leukemic blast transplantation into sub-lethally irradiated mice when used at concentrations of 5 and 10 ?M.

1.Picaud, S., Fedorov, O., Thanasopoulou, A., et al.Generation of a selective small molecule inhibitor of the CBP/p300 bromodomain for leukemia therapyCancer Res.75(23)5106-5119(2015)

Protocol

Cell experiment:

I-CBP112 is dissolved in DMSO and diluted with appropriate medium before use. Cells (6000 KG1a and 13000 LNCaP cells/well) are plated in 96-well flat-bottom plates approximately 24 h prior to drug treatment. After 24 h, 10–20% fetal bovine serum-containing medium is replaced with 2.5% serum medium, and cells are treated with I-CBP112 in 0.18% DMSO; 0.18% DMSO is shown to have negligible cell growth effects under the conditions used in our experiments. After being exposed to I-CBP112 for 66 h, cells are subjected to a final concentration of 0.476% [3H]thymidine per well and allowed to proliferate for an additional 6 h (exposure to I-CBP112 for a total of 72 h). Cells are harvested, and the counts of 3H in each well are taken relative to those treated with vehicle alone to quantify the effect of the ligand on proliferation[1].

Animal experiment:

Mice: Leukemic blasts expressing MLL-AF9 are treated in liquid culture with 5 μM of I-CBP112 for 3 days. Control cells are exposed to the corresponding concentration of the DMSO vehicle. Treated cells are then transplanted into sublethally irradiated syngeneic mice via tail vein injection. Upon the development of signs of disease the mice are sacrificed and analysed[2].

参考文献:

[1]. Zucconi BE, et al. Modulation of p300/CBP Acetylation of Nucleosomes by Bromodomain LigandI-CBP112. Biochemistry. 2016 Jul 12;55(27):3727-34.
[2]. Picaud S, et al. Generation of a Selective Small Molecule Inhibitor of the CBP/p300 Bromodomain for Leukemia Therapy. Cancer Res. 2015 Dec 1;75(23):5106-19.