Color Card 1.17985 - MQuant Potassium Test / Kalium-Test (Don't use printout for evaluation)
- Document Type:
- Technical Information
kalium
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114562 - Certificate of Quality - Spectroquant Potassium Cell Test / Kalium-Küvettentest / Test en cubetas Potasio
- Document Type:
- Certificate
- Product Catalog Number:
- 114562
- Product Catalog Name:
- Potassium Cell Test
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100615 - Certificate of Quality - Spectroquant Potassium Cell Test / Kalium-Küvettentest / Test en cubetas Potasio
- Document Type:
- Certificate
- Product Catalog Number:
- 100615
- Product Catalog Name:
- Potassium Cell Test
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Impact of terminal dimethylation on the resistance profile of α-N-heterocyclic thiosemicarbazones.
- Triapine is an α-N-heterocyclic thiosemicarbazone with promising anticancer activity against hematologic malignancies but widely ineffective against solid tumor types in clinical trials. The anticancer activity of thiosemicarbazones can be dramatically increased by terminal dimethylation. KP1089 is a gallium compound containing two terminal dimethylated thiosemicarbazone ligands. To gain insights on the vulnerability of this highly active terminal dimethylated thiosemicarbazone to drug resistance mechanisms, a new cell model with acquired resistance against the lead compound KP1089 was established. Subsequent genomic analyses (arrayCGH and FISH) revealed amplification of the ABCC1 gene on double minute chromosomal DNA in KP1089-resistant cells as well as overexpression of ABCC1 and ABCG2 on the protein level. KP1089 was further confirmed as a substrate of ABCC1 and ABCG2 but not of ABCB1 using a panel of ABC transporter-overexpressing cell models as well as ABC transporter inhibitors. Moreover, glutathione depletion strongly enhanced KP1089 activity, although no glutathione conjugate formation by glutathione-S-transferase was observed. Thus, a co-transport of KP1089 together with glutathione is suggested. Finally, a panel of thiosemicarbazone derivatives was tested on the new KP1089-resistant cell line. Notably, KP1089-resistant cells were not cross-resistant against thiosemicarbazones lacking terminal dimethylation (e.g. Triapine) which are less active than KP1089. This suggests that terminal dimethylation of thiosemicarbazones - linked with distinctly enhanced anticancer activity - leads to altered resistance profiles compared to classical thiosemicarbazones making this compound class of interest for further (pre)clinical evaluation.
- Document Type:
- Reference
- Product Catalog Number:
- MAB4146
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Color Card 109512 - Potassium iodide-starch paper / Kaliumiodid-Stärke-Papier Reag. Ph Eur (Don't use printout for evaluation!)
- Document Type:
- User Guide
- Product Catalog Number:
- 109512
- Product Catalog Name:
- Potassium iodide-starch paper