CUDC-101 - EGFR 抑制劑 - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemECUDC-101Cat. No.: HY-10223CAS No.: 1012054-59-9分式: CHNO分量: 434.49作靶點(diǎn): EGFR; HDAC作通路: JAK/STAT Signaling; Protein Tyrosine Kinase/RTK; CellCycle/DNA Damage; Epigenetics儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20

2、C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 25 mg/mL (57.54 mM; Need ultrasonic)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.75 mM); Clear solution2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (5.75 mM); Suspended solution; Need ultrasonic1/3 Master of Small Molecules 您邊的抑制

3、劑師www.MedChemEBIOLOGICAL ACTIVITY物活性 CUDC-101種效的 HDAC、EGFR 和 HER2 抑制劑，對(duì)應(yīng)的 IC50 值分別為 4.4、2.4 和 15.7 nM。IC50 & Target EGFR HER2 HDAC HDAC12.4 nM (IC50) 15.7 nM (IC50) 4.4 nM (IC50) 4.5 nM (IC50)HDAC2 HDAC3 HDAC4 HDAC612.6 nM (IC50) 9.1 nM (IC50) 13.2 nM (IC50) 5.1 nM (IC50)HDAC5 HDAC9 HDAC10 HDAC811.4

4、 nM (IC50) 67.2 nM (IC50) 26.1 nM (IC50) 79.8 nM (IC50)HDAC7373 nM (IC50)體外研究 CUDC-101 inhibits both class I and class II HDACs, but not class III, Sir-type HDACs. CUDC-101 displaysbroad antiproliferative activity in many human cancer cell types. CUDC-101 is a potent and selective HDAC,EGFR, and HER

5、2 inhibitor with only weak inhibition of the following protein kinases (IC50): KDR (VEGFR2)(849 nM), Src (11000 nM), Lyn (840 nM), Lck (5910 nM), Abl-1 (2890 nM), FGFR-2 (3430 nM), Flt-3 (1500nM), and Ret (3200 nM) 1. CUDC-101 (300 nM) inhibits both the full length AR (flAR) and the AR variantAR-V7

6、2. CUDC-101 is the most active agent in all three ATC cell lines screened for inhibitors of EGFR andHDACs, with half-maximal inhibitory concentration (IC50) at 0.15 M for 8505c, and 1.66 M for both C-643and SW-1736 cells. CUDC-101 inhibits cancer cell migration and modulates epithelial-mesenchymaltr

7、ansition marker expression in ATC cells. CUDC-101 also inhibits HDAC and MAPK pathway, induces p21,and decreases survivin and XIAP expression in ATC cells 3. CUDC-101 (1 M) increases the acetylation ofp53 and -tubulin, nonhistone substrates of HDAC, in treated cancer cells. CUDC-101 modulates RTKact

8、ivity and expression and exhibits immediate and stable inhibition of RTK and downstream Akt signaling4.體內(nèi)研究 CUDC-101 (120 mg/kg, iv, daily) induces tumor regression in the Hep-G2 liver cancer model and is moreefficacious than erlotinib at its maximum tolerated dose (MTD). In the erlotinib-resistant

9、A549 NSCLCxenograft model, CUDC-101 (120 mg/kg) shows potent inhibition of tumor growth. In the erlotinib-sensitiveH358 NSCLC models, CUDC-101 (15, 30, 60 mg/kg, i.v.) inhibits tumor growth in a dose-dependent manner.CUDC-101 (120 mg/kg) causes significant tumor regression in the lapatinib-resistant

10、, HER2-negative, EGFR-overexpressing MDA-MB-468 breast cancer model and the EGFR-overexpressing CAL-27 head and necksquamous cell carcinoma (HNSCC) model. CUDC-101 (120 mg/kg) also inhibits tumor growth in the K-rasmutant HCT116 colorectal and EGFR/HER2 (neu)-expressing HPAC pancreatic cancer models

11、 1. In an invivo mouse model of metastatic ATC, CUDC-101 inhibits tumor growth and metastases, and significantlyprolongs survival 3. CUDC-101 (120 mg/kg) is effective against a broad range of tumor types in xenograftmodels 4.PROTOCOL2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEKinase Assay 1 The

12、 activities of Class I and II HDACs are assessed using the Biomol Color de Lys system. Briefly, HeLa cellnuclear extracts are used as a source of HDACs. Different concentrations of drugs are added to HeLa cellnuclear extracts in the presence of a colorimetric artificial substrate. Developer is added

13、 at the end of theassay and enzyme activity is measured in the Wallac Victor II 1420 microplate reader at 405 nM.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 1 Cancer cell lines are plated at 5000 to 10000 cells per well in 96-well flat-bo

14、ttomed plates with varyingconcentrations of compounds. The cells are incubated with compounds for 72 h in the presence of 0.5% offetal bovine serum. Growth inhibition is assessed by an adenosine triphosphate (ATP) content assay usingthe Perkin-Elmer ATPlite kit.MCE has not independently confirmed th

15、e accuracy of these methods. They are for reference only.Animal Four- to six-week-old female athymic mice (nude nu/nu CD-1) are inoculated subcutaneously into the rightAdministration 1 hind flank region with 1 to 5106 cells in a medium suspension of 100200 L. For orthotopic implantation ofbreast can

16、cer cells, a cell suspension in 100 L of medium is injected directly into the mammary fat padsthrough a 27G needle. Different doses of CUDC-101, standard anticancer agents and vehicle areadministered orally, intraperitoneally, or via tail vein injection as indicated.MCE has not independently confirm

17、ed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093. Am J Cancer Res. 2018 Dec 1;8(12):2402-2418 Patent. US20180263995A1.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Xiong Cai et al Discovery of 7-(4-(3

18、-Ethynylphenylamino)-7-methoxyquinazolin-6-yloxy)-N-hydroxyheptanamide (CUDC-101) as a PotentMulti-Acting HDAC, EGFR, and HER2 Inhibitor for the Treatment of Cancer J. Med. Chem., 2010, 53 (5), pp 200020092. Sun H, et al. CUDC-101, a Novel Inhibitor of Full-Length Androgen Receptor (flAR) and Androgen Receptor Variant 7 (AR-V7) Activity:Mechanism of Action and In Vivo Efficacy. Horm Cancer. 2016 Jun;7(3):196-210.3. Zhang L, et al. Dual inhibition of HDAC