TMP195 - HDAC 抑制劑 - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemETMP195Cat. No.: HY-18361CAS No.: 1314891-22-9分式: CHFNO分量: 456.42作靶點(diǎn): HDAC作通路: Cell Cycle/DNA Damage; Epigenetics儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 100 mg/mL (219.10 mM)H2O : 40

2、% PEG300 5% Tween-80 45% salineSolubility: 3 mg/mL (6.57 mM); Clear solution2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 3 mg/mL (6.57 mM); Suspended solution; Need ultrasonic1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE3. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 3 mg/mL (6.57

3、 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 TMP195選擇性的IIa類組蛋脫酰酶 (HDAC) 抑制劑，對(duì)HDAC4，HDAC5，HDAC7，HDAC9的 Ki 值分別為59，60，26，5 nM。IC50 & Target HDAC9 HDAC7 HDAC5 HDAC49 nM (IC50) 46 nM (IC50) 106 nM (IC50) 111 nM (IC50)HDAC8 HDAC611700 nM (IC50) 47800 nM (IC50)體外研究 TMP195 blocks the accumulation of CCL2 prot

4、ein in the supernatants of monocyte-derived macrophagedifferentiation cultures. TMP195 significantly increases the amount of CCL1 protein secreted by themonocytes compared to vehicle group. In the transcriptional profiling data from the PHA-stimulated PBMCexperiments, CCL2 and CCL1 are respectively

5、down- or upregulated by TMP195 1. TMP195 occupies theacetyllysine-binding site of class IIa HDACs. TMP195 competes against binding of HDAC7 to a variety ofside-chain modifications on the same peptide backbone, despite no interference with the activity of otheracetyllysine reader proteins BRD4 (IC505

6、0 M) 2.體內(nèi)研究 TMP195 treatment alters the tumour microenvironment and reduces tumour burden and pulmonarymetastases by modulating macrophage phenotypes. TMP195 induces the recruitment and differentiation ofhighly phagocytic and stimulatory macrophages within tumors. Combining TMP195 with chemotherapyr

7、egimens or T-cell checkpoint blockade in this model significantly enhances the durability of tumour reduction2.PROTOCOLKinase Assay 2 Recombinant HDAC7 catalytic domain (amino acids 483-903) is labeled with DyLight 650 and applied to anarrayed library of 3,868 immobilized 20-mer peptides. Arrays are

8、 conducted using an automated TECANHS4 microarray processing station, initiated by incubation with blocking buffer for 30 min at 30C followed byishing with saline containing 50 mM Tris Base and 0.1% Tween-20 (pH 7.2) before incubation with thelabeled HDAC7 protein for 120 min at 4C. In the case of T

9、MP195 competition experiments, the labeledprotein is pre-incubated with TMP195 for 30 min before application to the array. The microarrays are thenished before being dried and imaged with an scanner 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Anim

10、al Mice: For all mouse experiments, mice are treated with intraperitoneal (i.p.) injections of 50 L of the vehicleAdministration 2 dimethyl sulfoxide (DMSO) or 50 L of TMP195 dissolved in 100% DMSO at a final concentration of 50 mgper kg daily 2.2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEMCE h

11、as not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) J Mol Med (Berl). 2019 Jun 14. Nat Biomed Eng. 2018;2:578-588.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Lobera M, et al. Selective class IIa histone deacetylase inhibition via a nonchelating zinc-binding group. Nat Chem Biol. 2013May;9(5):319-25.2. Guerriero JL, et al. Class IIa HDAC inhibition reduces breast tumors and metastases through anti-tumor macrophages. Nature. 2017Mar 16;543(7645):428-432.McePdfHeightCaution: Prod