Dp44mT

Dp44mT is an iron chelator, possessing DNA-damaging activity mediated by top2a inhibition.

Product information

CAS Number: 152095-12-0

Molecular Weight: 285.37

Formula: C14H15N5S

Synonym:

Iron Chelator

ACMC-20f6dm

HY-18973

Dp44mT

152095-12-0

Iron Chelator, Dp44mT

3-(Dipyridin-2-ylmethylideneamino)-1,1-dimethylthiourea

Hydrazinecarbothioamide, 2-(di-2-pyridinylmethylene)-N,N-dimethyl-

2,N-dimethylsemicarbazone

Dp-44mT

2,2′-Dipyridyl-N,N-dimethylsemicarbazone

CHEMBL385064

SCHEMBL1025308

CTK0B1402

DTXSID80438322

BCP15939

EX-A2542

ZINC3986690

Dp44mT, &gt

NSC744381

s7909

CCG-267326

NSC-744381

AK647019

BS-15546

CS-0014820

di-2-pyridyl ketone 4,4-dimethylthiosemicarbazone

J-008883

3-[bis(2-pyridyl)methyleneamino]-1,1-dimethyl-thiourea

2-(Di(pyridin-2-yl)methylene)-N,N-dimethylhydrazinecarbothioamide

2-[di(Pyridin-2-yl)methylidene]-N,N-dimethylhydrazinecarbothioamide

Chemical Name: 3-(Dipyridin-2-ylmethylideneamino)-1,1-dimethylthiourea

Smiles: CN(C)C(=S)NN=C(C1=CC=CC=N1)C1=CC=CC=N1

InChiKey: XOBIGRNRXCAMJQ-UHFFFAOYSA-N

InChi: 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)

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

Dp44mT is cytotoxic to breast cancer cells, at least in part, due to selective inhibition of top2α. Dp44mT alone induced selective cell killing in the breast cancer cell line MDA-MB-231 when compared with healthy mammary epithelial cells (MCF-12A). It induces G1 cell cycle arrest and reduces cancer cell clonogenic growth at nanomolar concentrations. Dp44mT, but not the iron chelator desferal, induces DNA double-strand breaks quantified as S139 phosphorylated histone foci (γ-H2AX) and Comet tails induced in MDA-MB-231 cells. Doxorubicin-induced cytotoxicity and DNA damage are both enhanced significantly in the presence of low concentrations of Dp44mT. The chelator caused selective poisoning of DNA topoisomerase IIα (top2α) as measured by an in vitro DNA cleavage assay and cellular topoisomerase-DNA complex formation. Dp44mT targets lysosome integrity through copper binding. Copper binding is essential for the potent antitumor activity of Dp44mT, as coincubation with nontoxic copper chelators markedly attenuated its cytotoxicity.

References:

1. Al-Akra L, Bae DH, Sahni S, Huang MLH, Park KC, Lane DJR, Jansson PJ, Richardson DR. Tumor stressors induce two mechanisms of intracellular p-glycoprotein-mediated resistance that are overcome by lysosomal-targeted thiosemicarbazones. J Biol Chem. 2018 Jan 5. pii: jbc.M116.772699. doi: 10.1074/jbc.M116.772699. [Epub ahead of print] PubMed PMID: 29305422.
2. Kang YJ, Kuo CF, Majd S. Nanoparticle-based delivery of an anti-proliferative metal chelator to tumor cells. Conf Proc IEEE Eng Med Biol Soc. 2017 Jul;2017:309-312. doi: 10.1109/EMBC.2017.8036824. PubMed PMID: 29059872.
3. Moussa RS, Kovacevic Z, Bae DH, Lane DJR, Richardson DR. Transcriptional regulation of the cyclin-dependent kinase inhibitor, p21(CIP1/WAF1), by the chelator, Dp44mT. Biochim Biophys Acta. 2017 Oct 13. pii: S0304-4165(17)30330-6. doi: 10.1016/j.bbagen.2017.10.009. [Epub ahead of print] PubMed PMID: 29032246.

Products are for research use only. Not for human use.