CHM 1 - CAS 154554-41-3
Category: Inhibitor
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Molecular Formula:
C16H10FNO3
Molecular Weight:
283.25
COA:
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Targets:
Microtubule/Tubulin
Description:
CHM 1 is an apoptosis inducer with potent antitumor activity in human hepatocellular carcinoma. It inhibits tubulin polymerization in vitro and in vivo, and results in cell cycle arrest at G2/M phase by activating Cdc2 kinase activity. CHM 1 also exhibits vascular targeting activity via upregulation of p53 and induction of death receptor (DR5)-mediated apoptosis in HUVEC cells.
Brife Description:
apoptosis inducer
Purity:
≥99% by HPLC
Synonyms:
CHM-1; CHM 1; CHM1; NSC 656158; NSC-656158; NSC656158; 6-(2-Fluorophenyl)-1,3-dioxolo[4,5-g]quinolin-8(5H)-one
MSDS:
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Application:
antitumor agent
InChIKey:
ZMYDAPJHGNEFGQ-UHFFFAOYSA-N
InChI:
InChI=1S/C16H10FNO3/c17-11-4-2-1-3-9(11)12-6-14(19)10-5-15-16(21-8-20-15)7-13(10)18-12/h1-7H,8H2,(H,18,19)
Canonical SMILES:
C1OC2=C(O1)C=C3C(=C2)C(=O)C=C(N3)C4=CC=CC=C4F
1.Design and synthesis of 2-(3-benzo[b]thienyl)-6,7-methylenedioxyquinolin-4-one analogues as potent antitumor agents that inhibit tubulin assembly.
Chang YH;Hsu MH;Wang SH;Huang LJ;Qian K;Morris-Natschke SL;Hamel E;Kuo SC;Lee KH J Med Chem. 2009 Aug 13;52(15):4883-91. doi: 10.1021/jm900456w.
As part of our continuing investigation of azo-flavonoid derivatives as potential anticancer drug candidates, a series of 2-aryl-6,7-methylenedioxyquinolin-4-one analogues was designed and synthesized. The design combined structural features of 2-(2-fluorophenyl)-6,7-methylenedioxyquinolin-4-one (CHM-1), a previously discovered compound with potent in vivo antitumor activity, and 2-arylquinolin-4-ones, identified by CoMFA models. The newly synthesized analogues were evaluated for cytotoxicity against seven human cancer cell lines, and structure-activity relationship (SAR) correlations were established. Analogues 1, 37, and 39 showed potent cytotoxicity against different cancer cell lines. Compound 1 demonstrated selective cytotoxicity against Hep 3B (hepatoma) cells. Compound 37 was cytotoxic against HL-60 (leukemia), HCT-116 (colon cancer), Hep 3B (hepatoma), and SK-MEL-5 (melanoma) cells. Compound 39 exhibited broad cytotoxicity against all seven cancer cell lines, with IC50 values between 0.07 and 0.19 microM. Results from mechanism of action studies revealed that these new quinolone derivatives function as antitubulin agents.
2.CHM-1, a novel synthetic quinolone with potent and selective antimitotic antitumor activity against human hepatocellular carcinoma in vitro and in vivo.
Wang SW;Pan SL;Huang YC;Guh JH;Chiang PC;Huang DY;Kuo SC;Lee KH;Teng CM Mol Cancer Ther. 2008 Feb;7(2):350-60. doi: 10.1158/1535-7163.MCT-07-2000.
Hepatocellular carcinoma is highly chemoresistant to currently available chemotherapeutic agents. In this study, 2'-fluoro-6,7-methylenedioxy-2-phenyl-4-quinolone (CHM-1), a synthetic 6,7-substituted 2-phenyl-4-quinolone, was identified as a potent and selective antitumor agent in human hepatocellular carcinoma. CHM-1 induced growth inhibition of HA22T, Hep3B, and HepG2 cells in a concentration-dependent manner but did not obviously impair the viability of normal cells at the IC(50) for liver cancer cells. CHM-1-induced apoptosis was also characterized by immunofluorescence microscopy. CHM-1 interacted with tubulin at the colchicine-binding site, markedly inhibited tubulin polymerization both in vitro and in vivo, and disrupted microtubule organization. CHM-1 caused cell cycle arrest at G(2)-M phase by activating Cdc2/cyclin B1 complex activity. CHM-1-induced cell death, activation of Cdc2 kinase activity, and elevation of MPM2 phosphoepitopes were profoundly attenuated by roscovitine, a specific cyclin-dependent kinase inhibitor. CHM-1 did not modulate the caspase cascade, and the pan-caspase-inhibitor z-VAD-fmk did not abolish CHM-1-induced cell death. However, CHM-1 induced the translocation of apoptosis-inducing factor (AIF) from mitochondria to the nucleus.
3.Inhibition of the insulin-like growth factor 1 receptor by CHM-1 blocks proliferation of glioblastoma multiforme cells.
Lin YC;Hou SC;Hung CM;Lin JN;Chen WC;Ho CT;Kuo SC;Way TD Chem Biol Interact. 2015 Apr 25;231:119-26. doi: 10.1016/j.cbi.2015.01.016. Epub 2015 Jan 30.
The insulin-like growth factor-1 receptor (IGF-1R) plays a pivotal role in transformation, growth, and survival of glioblastoma multiforme (GBM) cells, and has emerged as a general and promising target for cancer treatment. In this study, we examined the anti-tumor effects of CHM-1, a synthetic 6,7-methylenedioxy substituted 2-phenyl-4-quinolone derivative, on GBM cells in vitro and in vivo. CHM-1 selectively blocked IGF-1R auto-phosphorylation, with an ability to distinguish between IGF-1R and related tyrosine kinase receptors, such as insulin receptor (IR), epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR), and fibroblast growth factor receptor (FGFR). Further investigation revealed that, the phosphorylation of ERK1/2 as well as Akt was inhibited in CHM-1 treated GBM8401 cells possibly through the selective blockage of IGF-1R auto-phosphorylation. Our study also showed that p.o. treatment with the hydrophilic dihydrogen phosphate CHM-1P reduced the tumor volumes of the GBM8401 derived tumors in mouse brain and also prolonged the survival rate. The results provided potential opportunities for effective chemotherapy for GBM.
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CAS 154554-41-3 CHM 1

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