Iron Chelator, Dp44mT Struktur

Iron Chelator, Dp44mT

Bezeichnung:Iron Chelator, Dp44mT

CAS-Nr152095-12-0

Englisch Name:Iron Chelator, Dp44mT

CBNumberCB52524488

SummenformelC14H15N5S

Molgewicht285.37

MOL-Datei152095-12-0.mol

Iron Chelator, Dp44mT physikalisch-chemischer Eigenschaften

storage temp.	2-8°C
Löslichkeit	DMSO: ≥5mg/mL
Aggregatzustand	powder
Farbe	yellow to orange
Sensitive	Light Sensitive
Stabilität	Stable for 1 year from date of purchase as supplied. Solutions in DMSO may ne stored at -20°C for 1 month.

Sicherheit

Kennzeichnung gefährlicher	Xn
R-Sätze:	22
RIDADR	UN 2811 6.1 / PGIII
WGK Germany	3
HazardClass	6.1

Gefahreninformationscode (GHS)

Iron Chelator, Dp44mT Chemische Eigenschaften,Einsatz,Produktion Methoden

Beschreibung
Dp44mT (152095-12-0) is a metal chelator with potent antitumor activity.1,2?It displayed an average IC50?of 30 nM over 28 cancer cell lines (IC50?range was 5 nM to 400 nM).2?Dp44mT retained its antiproliferative activity in both etoposide-resistant MCF-7/VP clones (MCF-7 breast cancer cells) and vinblastine-resistant KB-VB1 clones (KB3-1 epidermoid carcinoma cells) with an IC50?= 12 nM for both lines.2?The potency of Dp44mT has been attributed to the high redox activity of the Dp44mT-Fe complex leading to cytotoxic ROS generation. The antitumor activity of Dp44mT may also be mediated by a redox active copper complex that causes cellular glutathione depletion and lysosomal damage.3,4?It also inhibited T-cell activation and prevented CD25 up-regulation?via?a copper-dependent mechanism.5?Dp44mT has recently been shown to effectively inhibit c-Met though metalloprotease-mediated cleavage and lysosomal degradation.6
Verwenden
Iron Chelator, Dp44mT is a cell-permeable di-2-pyridyl thiosemicarbazone (DpT) based tridentate ligand.
Biochem/physiol Actions
Dp44mT (di-2-pyridylketone-4,4,-dimethyl-3-thiosemicarbazone) influences lysosome integrity through copper binding. It induces reactive oxygen species (ROS) generation by redox cycling of iron complex. Dp44mT exhibits anti cancer action by attenuating Ndrg-1 (N-myc downstream regulated 1), a metastasis suppressor protein. It also alters the cyclin family of proteins (A, B, D1, D2,D3 and cyclin-dependent kinase 2) known for cell-cycle regulation. Dp44mT is known to promote apoptosis in neuroepithelioma, melanoma and breast cancer.
in vivo
6 and 24 hours after the treatment with 0.1 and 1 μmol/l of dp44mt, the treatment resulted in the covalent complex formation between dna and top2α. no complex formation was found after the treatment when probed for top1 or top2β. caspase inhibitor pretreatment did not rescue the formation of top2α complex, so the formed top2α-dna complexes were not the secondary effect of apoptosis [1].
Einzelnachweise
1) Yuan?et al.?(2004),?Novel di-2-pyridyl-derived iron chelators with marked and selective antitumor activity: in vitro and in vivo assessment;?Blood,?104?1450 2) Whitnall?et al.?(2006),?A class of iron chelators with a wide spectrum of potent antitumor activity that overcomes resistance to chemotherapeutics., Proc. Natl. Acad. Sci. USA?103?14910 3) Lovejoy?et al. (2011),?Antitumor activity of metal-chelating compound Dp44mT is mediated by formation of a redox-active copper complex that accumulates in lysosomes; Cancer Res.,?71?5871 4) Gutierrez?et al.?(2014),?The anticancer agent di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbzone (Dp44mT) overcomes prosurvival autophagy by two mechanisms: persistent reduction of autophagosome synthesis and impairment of lysosomal integrity; J. Biol. Chem.,?289?33568 5) Gundelach?et al.?(2013),?The anticancer drug Dp344mT inhibits T-cell activation and CD25 through a copper-dependent mechanism; FASEB J.,?27?782 6)Park?et al. (2020),?Thiosemicarbazones suppress expression of the c-Met oncogene by mechanisms involving lysosomal degradation and intracellular shedding;?J. Biol.Chem.,?295?481

Iron Chelator, Dp44mT Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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