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| | Iron Chelator, Dp44mT Basic information |
| Product Name: | Iron Chelator, Dp44mT | | Synonyms: | Iron Chelator, Dp44mT;2-(Di-2-pyridinylmethylene)-N,N-dimethyl-hydrazinecarbothioamide;Di-2-pyridylketone-4,4,-dimethyl-3-thiosemicarbazone;Dp44mT;de44mt;CS-2521;Iron Chelator;Hydrazinecarbothioamide, 2-(di-2-pyridinylmethylene)-N,N-dimethyl- | | CAS: | 152095-12-0 | | MF: | C14H15N5S | | MW: | 285.37 | | EINECS: | 694-427-5 | | Product Categories: | | | Mol File: | 152095-12-0.mol |  |
| | Iron Chelator, Dp44mT Chemical Properties |
| storage temp. | 2-8°C | | solubility | DMSO: ≥5mg/mL | | form | powder | | color | yellow to orange | | Sensitive | Light Sensitive | | Stability: | Stable for 1 year from date of purchase as supplied. Solutions in DMSO may ne stored at -20°C for 1 month. | | InChI | 1S/C14H15N5S/c1-19(2)14(20)18-17-13(11-7-3-5-9-15-11)12-8-4-6-10-16-12/h3-10H,1-2H3,(H,18,20) | | InChIKey | XOBIGRNRXCAMJQ-UHFFFAOYSA-N | | SMILES | CN(C)C(=S)N\N=C(\c1ccccn1)c2ccccn2 |
| Hazard Codes | Xn | | Risk Statements | 22 | | RIDADR | UN 2811 6.1 / PGIII | | WGK Germany | 3 | | HazardClass | 6.1 | | Storage Class | 6.1C - Combustible acute toxic Cat.3
toxic compounds or compounds which causing chronic effects | | Hazard Classifications | Acute Tox. 3 Oral |
| | Iron Chelator, Dp44mT Usage And Synthesis |
| Description | Dp44mT (152095-12-0) is a metal chelator with potent antitumor activity.1,2It displayed an average IC50of 30 nM over 28 cancer cell lines (IC50range was 5 nM to 400 nM).2Dp44mT 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.2The 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.3,4It also inhibited T-cell activation and prevented CD25 up-regulationviaa copper-dependent mechanism.5Dp44mT 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] JUN YUAN Des R R David B Lovejoy. Novel di-2-pyridyl-derived iron chelators with marked and selective antitumor activity: in vitro and in vivo assessment.[J]. Blood, 2004, 104 5: 1450-1458. DOI:10.1182/blood-2004-03-0868
[2] MEGAN WHITNALL. A class of iron chelators with a wide spectrum of potent antitumor activity that overcomes resistance to chemotherapeutics.[J]. ACS Catalysis , 2006: 14901-14906. DOI:10.1073/pnas.0604979103
[3] DAVID B LOVEJOY. Antitumor activity of metal-chelating compound Dp44mT is mediated by formation of a redox-active copper complex that accumulates in lysosomes.[J]. Cancer research, 2011, 71 17: 5871-5880. DOI:10.1158/0008-5472.can-11-1218
[4] ELAINE GUTIERREZ P J J Des R Richardson. The anticancer agent di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT) overcomes prosurvival autophagy by two mechanisms: persistent induction of autophagosome synthesis and impairment of lysosomal integrity.[J]. The Journal of Biological Chemistry, 2014, 289 48: 33568-33589. DOI:10.1074/jbc.m114.599480
[5] JUSTIN H. GUNDELACH. The anticancer drug Dp44mT inhibits T-cell activation and CD25 through a copper-dependent mechanism[J]. FASEB Journal, 2012, 27 2: 782-792. DOI:10.1096/fj.12-215756
[6] K. PARK. Thiosemicarbazones suppress expression of the c-Met oncogene by mechanisms involving lysosomal degradation and intracellular shedding[J]. The Journal of Biological Chemistry, 2019, 110 1: 481-503. DOI:10.1074/jbc.ra119.011341 |
| | Iron Chelator, Dp44mT Preparation Products And Raw materials |
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