Dp44mT is an iron chelator, possessing DNA-damaging activity mediated by top2a inhibition.
CAS Number: 152095-12-0
Molecular Weight: 285.37
Iron Chelator, Dp44mT
di-2-pyridyl ketone 4,4-dimethylthiosemicarbazone
Chemical Name: 3-(Dipyridin-2-ylmethylideneamino)-1,1-dimethylthiourea
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
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.
- 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.
- 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.
- 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.
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