152095-12-0

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
• CAS NO: 152095-12-0
• Molecular Formula: C14H15N5S
• Molecular Weight: 285.3674
• EINECS: -0
• Mol File: 152095-12-0.mol

Chemical Properties

• Appearance: yellow to orange/
• Storage Temp.: 2-8°C
• Solubility: DMSO: ≥5mg/mL
• 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.
• CAS DataBase Reference: Iron Chelator, Dp44mT(CAS DataBase Reference)
• NIST Chemistry Reference: Iron Chelator, Dp44mT(152095-12-0)
• EPA Substance Registry System: Iron Chelator, Dp44mT(152095-12-0)

Safety Data

• Hazard Codes: Xn
• Statements: 22
• RIDADR: UN 2811 6.1 / PGIII
• WGK Germany: 3
• HazardClass: 6.1
• Hazardous Substances Data: 152095-12-0(Hazardous Substances Data)

Usage

Uses

Used in Anticancer Applications:
Iron Chelator, Dp44mT is used as an antitumor agent for its potent activity against various cancer cell lines. The expression is: Iron Chelator, Dp44mT is used as an antitumor agent for its ability to generate cytotoxic ROS and cause cellular glutathione depletion and lysosomal damage.
Used in Overcoming Drug Resistance:
Iron Chelator, Dp44mT is used as a chemosensitizer for its ability to retain antiproliferative activity in 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 of 12 nM for both lines. The expression is: Iron Chelator, Dp44mT is used as a chemosensitizer for its effectiveness in overcoming drug resistance in cancer cells.
Used in Immunomodulation:
Iron Chelator, Dp44mT is used as an immunomodulatory agent for its ability to inhibit T-cell activation and prevent CD25 up-regulation via a copper-dependent mechanism. The expression is: Iron Chelator, Dp44mT is used as an immunomodulatory agent for its role in regulating immune cell activation and function.
Used in Targeting c-Met:
Iron Chelator, Dp44mT is used as a targeting agent for its ability to effectively inhibit c-Met through metalloprotease-mediated cleavage and lysosomal degradation. The expression is: Iron Chelator, Dp44mT is used as a targeting agent for its effectiveness in inhibiting c-Met, a key player in cancer progression and metastasis.
Used in Pharmaceutical Industry:
Iron Chelator, Dp44mT is used as a key component in the development of novel anticancer drugs and therapies due to its multifaceted mechanisms of action and potential to overcome drug resistance. The expression is: Used in Pharmaceutical Industry, Iron Chelator, Dp44mT is used as a key component in the development of novel anticancer drugs and therapies for its diverse applications in cancer treatment.

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

Upstream product

• 19437-26-4 2,2'-dipyridyl ketone 
• 6926-58-5 4,4-dimethylthiosemicarbazide 

Relevant articles and documents

Dipyridyl thiosemicarbazone chelators with potent and selective antitumor activity form iron complexes with redox activity

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

Analysis of the interaction of Dp44mT with human serum albumin and calf thymus DNA using molecular docking and spectroscopic techniques

Di-2-pyridylketone-4,4,-dimethyl-3-thiosemicarbazone (Dp44mT) exhibits significant antitumor activity. However, the mechanism of its pharmacological interaction with human serum albumin (HSA) and DNA remains poorly understood. Here, we aimed to elucidate the interactions of Dp44mT with HSA and DNA using MTT assays, spectroscopic methods, and molecular docking analysis. Our results indicated that addition of HSA at a ratio of 1:1 did not alter the cytotoxicity of Dp44mT, but did affect the cytotoxicity of the Dp44mT-Cu complex. Data from fluorescence quenching and UV-VIS absorbance measurements demonstrated that Dp44mT could bind to HSA with a moderate affinity (Ka = approximately 104 M-1). CD spectra revealed that Dp44mT could slightly disrupt the secondary structure of HSA. Dp44mT could also interact with Ct-DNA, but had a moderate binding constant (KEB = approximately 104 M-1). Docking studies indicated that the IB site of HSA, but not the IIA and IIIA sites, could be favorable for Dp44mT and that binding of Dp44mT to HSA involved hydrogen bonds and hydrophobic force, consistent with thermodynamic results from spectral investigations. Thus, the moderate binding affinity of Dp44mT with HSA and DNA partially contributed to its antitumor activity and may be preferable in drug design approaches.

Semicarbazide derivatives and pharmaceutical compositions and uses thereof

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.

Anticancer activity of the thiosemicarbazones that are based on di-2-pyridine ketone and quinoline moiety

Thiosemicarbazones (TSC) are a subclass of iron-chelating agents that are believed to have an anticancer activity. The high potential for the application of this compound class can be illustrated by a fact that three TSC have entered clinical trials. The ability to chelate metal ions results in several biochemical changes in the cellular metabolism and growth. An important factor that determines the antitumor activity of TSC is a level of iron regulatory proteins and the antioxidant potential that is specific for each type of cancer cell. However, despite the increasing interest in TSC, their mechanism of anticancer activity is still unclear. For a more effective and rational design, it is crucial to determine and describe the abovementioned issues. In this report, we describe a series of new TSC that are designed on the four main structural scaffolds. The anticancer activity of these compounds was evaluated against a panel of cancer cell lines including colon and breast cancers and gliomas. Special attention was paid to the metal-dependent proteins. The impact of the tested TSC on the cell cycle and redox homeostasis was also determined. These results confirm a p53-independent mechanism of apoptosis.

A copper metal complex and its and human serum albumin complex and their synthetic method and application

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).

Improved cytotoxicity of pyridyl-substituted thiosemicarbazones against MCF-7 when used as metal ionophores

Zinc is the second most abundant transition metal in the human body, between 3 and 10 % of human genes encoding for zinc binding proteins. We have investigated the interplay of reactive oxygen species and zinc homeostasis on the cytotoxicity of the thiose

METAL ION CHELATORS AND THERAPEUTIC USE THEREOF

The present invention relates to compounds which are capable of chelating metal ions. In particular, the present invention relates to (thio)semicarbazone compounds and (thio)hydrazone compounds which are capable of chelating metal ions, including iron ions. Also disclosed are therapeutic use of such compounds and/or their metal ion complexes, including methods of treating diseases associated with cell proliferation.