CUDC-101

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

一种有效的多靶点 HDAC、EGFR 和 HER2 抑制剂，IC50 分别为 4.4、2.4 和 15.7 nM。

A potent, multi-targeted HDAC, EGFR and HER2 inhibitor with IC50 of 4.4, 2.4, and 15.7 nM, respectively; Exhibits efficient antiproliferative activity with greater potency (IC50<1 uM) than Vorinostat (SAHA), Erlotinib, Lapatinib; Promotes tumor regression or inhibition in various cancer xenograft models including NSCLC, liver, breast, head and neck, colon, and pancreatic cancers. Solid TumorsPhase 1 Discontinued(In Vitro):CUDC-101 inhibits both class I and class II HDACs, but not class III, Sir-type HDACs. CUDC-101 displays broad antiproliferative activity in many human cancer cell types. CUDC-101 is a potent and selective HDAC, EGFR, and HER2 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 (1500 nM), and Ret (3200 nM). CUDC-101 (300 nM) inhibits both the full length AR (flAR) and the AR variant AR-V7. CUDC-101 is the most active agent in all three ATC cell lines screened for inhibitors of EGFR and HDACs, with half-maximal inhibitory concentration (IC50) at 0.15 μM for 8505c, and 1.66 μM for both C-643 and SW-1736 cells. CUDC-101 inhibits cancer cell migration and modulates epithelial-mesenchymal transition marker expression in ATC cells. CUDC-101 also inhibits HDAC and MAPK pathway, induces p21, and decreases survivin and XIAP expression in ATC cells. CUDC-101 (1 μM) increases the acetylation of p53 and α-tubulin, nonhistone substrates of HDAC, in treated cancer cells. CUDC-101 modulates RTK activity and expression and exhibits immediate and stable inhibition of RTK and downstream Akt signaling. (In Vivo):CUDC-101 (120 mg/kg, iv, daily) induces tumor regression in the Hep-G2 liver cancer model and is more efficacious than erlotinib at its maximum tolerated dose (MTD). In the erlotinib-resistant A549 NSCLC xenograft model, CUDC-101 (120 mg/kg) shows potent inhibition of tumor growth. In the erlotinib-sensitive H358 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, HER2-negative, EGFR-overexpressing MDA-MB-468 breast cancer model and the EGFR-overexpressing CAL-27 head and neck squamous cell carcinoma (HNSCC) model. CUDC-101 (120 mg/kg) also inhibits tumor growth in the K-ras mutant HCT116 colorectal and EGFR/HER2 (neu)-expressing HPAC pancreatic cancer models. In an in vivo mouse model of metastatic ATC, CUDC-101 inhibits tumor growth and metastases, and significantly prolongs survival. CUDC-101 (120 mg/kg) is effective against a broad range of tumor types in xenograft models.

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CUDC101 | CUDC 101

Cell Cycle/DNA Damage

HDAC

EGFR|HDAC|HDAC1|HDAC10|HDAC2|HDAC3|HDAC4|HDAC5|HDAC6|HDAC7|HDAC8|HDAC9|HER2

Cancer

Solid Tumors

1012054-59-9

434.4876

C24H26N4O4

>98% (HPLC)

10 mM in DMSO

O=C(NO)CCCCCCOC1=CC2=C(NC3=CC=CC(C#C)=C3)N=CN=C2C=C1OC

Heptanamide, 7-[[4-[(3-ethynylphenyl)amino]-7-methoxy-6-quinazolinyl]oxy]-N-hydroxy-

(-20℃)

With Ice Pack

≥ 2 years