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Combination of a CDK inhibitor and mitoxantrone

A technology of mitoxantrone and inhibitors, applied in the combined field of CDK inhibitors and mitoxantrone

Inactive Publication Date: 2005-12-14
CYCLACEL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Indeed, early results suggest that transformed and normal cells differ in their requirements for e.g. cyclin A / CDK2, thus opening up the possibility of developing new antineoplastic agents that are not observed with conventional cytotoxic and cytostatic drugs Common Host Toxicity

Method used

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  • Combination of a CDK inhibitor and mitoxantrone
  • Combination of a CDK inhibitor and mitoxantrone
  • Combination of a CDK inhibitor and mitoxantrone

Examples

Experimental program
Comparison scheme
Effect test

Embodiment Construction

[0073] The growth inhibitory activity of roscovitine alone and in combination with mitoxantrone on the PC-3 prostate cell line was determined using a monolayer assay and a tumor stem cell assay.

[0074] Methods and materials

[0075] compound

[0076] Stock solutions of CDK inhibitors (eg roscovitine) were prepared in DMSO and aliquots were stored at -20°C. Final dilutions were prepared in culture medium (Iscove's Modified Dulbecco's Medium; Life Technologies, Karlsruhe) immediately before use.

[0077] clonogenic analysis

[0078] Preparation of Single Cell Suspensions from Human Tumor Xenografts

[0079] Solid human tumor xenografts grown in subcutaneous serial passages in nude mice with thymic hypoplasia (NMRI, Naval Medical Research Institute, USA, nu / nu strain, obtained from our own breeding facility) were excised under sterile conditions, mechanically. Decomposition, followed by incubation at 37°C for 30 minutes with an enzyme mixture consisting of collagenase (...

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Abstract

A first aspect of the invention relates to a combination comprising a CDK inhibitor and mitoxantrone. A second aspect of the invention relates to a pharmaceutical product comprising a CDK inhibitor and mitoxantrone as a combined preparation for simultaneous, sequential or separate use in therapy. A third aspect of the invention relates to a method of treating a proliferative disorder, said method comprising simultaneously, sequentially or separately administering a CDK inhibitor and mitoxantrone to a subject.

Description

field of invention [0001] The present invention relates to drug combinations suitable for the treatment of cancer and other proliferative diseases. Background of the invention [0002] Initiation, progression, and termination of the mammalian cell cycle are regulated by various cyclin-dependent kinase (CDK) complexes that are critical for cell growth. These complexes include at least one catalytic subunit (CDK itself) and one regulatory subunit (cyclins). Some of the more important complexes for cell cycle regulation include cyclin A (CDK1 - also known as cdc2, and CDK2), cyclins B1-B3 (CDK1), cyclin C (CDK8), cyclin D1 - D3 (CDK2, CDK4, CDK5, CDK6), cyclin E (CDK2), cyclins K and T (CDK9) and cyclin H (CDK7). Each of these complexes is involved in a specific phase of the cell cycle. [0003] The activity of CDKs is regulated post-translationally through transient associations with other proteins and changes in their intracellular localization. Tumor development is stron...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/137A61K31/52A61P35/00
CPCA61K31/52A61K31/137A61P35/00A61P43/00Y02A50/30A61K2300/00
Inventor 阿索斯·贾内拉-博尔-拉多里
Owner CYCLACEL