152095-12-0 Usage
Description
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
Uses
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].
References
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
Check Digit Verification of cas no
The CAS Registry Mumber 152095-12-0 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,5,2,0,9 and 5 respectively; the second part has 2 digits, 1 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 152095-12:
(8*1)+(7*5)+(6*2)+(5*0)+(4*9)+(3*5)+(2*1)+(1*2)=110
110 % 10 = 0
So 152095-12-0 is a valid CAS Registry Number.
152095-12-0Relevant articles and documents
Dipyridyl thiosemicarbazone chelators with potent and selective antitumor activity form iron complexes with redox activity
Richardson, Des R.,Sharpe, Philip C.,Lovejoy, David B.,Senaratne, Dakshita,Kalinowski, Danuta S.,Islam, Mohammad,Bernhardt, Paul V.
, p. 6510 - 6521 (2006)
There has been much interest in the development of iron (Fe) chelators for the treatment of cancer. We developed a series of di-2-pyridyl ketone thiosemicarbazone (HDpT) ligands which show marked and selective antitumor activity in vitro and in vivo. In t
Semicarbazide derivatives and pharmaceutical compositions and uses thereof
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Paragraph 0169-0171, (2020/05/11)
The invention relates to a selenosemicarbazone derivative, and a pharmaceutical composition and an application thereof. Specifically, the invention relates to a compound shown as a formula I or an isomer thereof, a pharmaceutically acceptable salt, a composition comprising the compound shown as the general formula I or the isomer thereof, the pharmaceutically acceptable salt and a pharmaceutically acceptable vector, and applications of the compound shown as the general formula I or the isomer thereof and the pharmaceutically acceptable salt in preparing drugs for resisting tumor or treating diseases or symptoms related to the tumor. The formula I is shown in the description.
A copper metal complex and its and human serum albumin complex and their synthetic method and application
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Paragraph 0033; 0034; 0035; 0036; 0037; 0051-0052; 0054-0055, (2017/08/26)
The invention discloses a copper metal complex and a compound of copper metal complex and human serum albumin, as well as synthesis methods and application of the copper metal complex and the compound. The synthesis method for the copper metal complex comprises the following steps of reacting 2-di-pyridyl ketone with 4,4minute-dimethyl-3-thiosemicarbazide to generate precipitates by taking an alcohol substance as a solvent, and collecting and washing the precipitates to obtain ligands; reacting the ligands with CuCl2.2H2O by taking an alcohol substance as a solvent, standing and crystallizing a reaction product, and collecting crystals to obtain the copper metal complex. The compound is obtained by incubating the copper metal complex and the human serum albumin by adopting a solution method. The structure of the copper metal complex is shown in Formula (I).
