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Novel combinations of a tubulin polymerization inhibitor and a poly (adp-ribose) polymerase (PARP) inhibitor for use in the treatment of cancer

A technology of polymerization inhibitor and tubulin, which can be used in medical preparations containing active ingredients, anti-tumor drugs, anti-infective drugs, etc., and can solve problems such as unmet medical needs.

Pending Publication Date: 2020-11-13
NOVIGA RES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Therefore, there is a gap in the market to address this large unmet medical need for novel second-line therapies targeting this patient population

Method used

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  • Novel combinations of a tubulin polymerization inhibitor and a poly (adp-ribose) polymerase (PARP) inhibitor for use in the treatment of cancer
  • Novel combinations of a tubulin polymerization inhibitor and a poly (adp-ribose) polymerase (PARP) inhibitor for use in the treatment of cancer
  • Novel combinations of a tubulin polymerization inhibitor and a poly (adp-ribose) polymerase (PARP) inhibitor for use in the treatment of cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0200] Antitumor Efficacy of NOV202 Alone and in Combination with Olaparib in Patient-Derived Ovarian Cancer Xenografts (Ov10584)

[0201] NMRI was used as follows: nu / nu female (Janvier) mice (8 weeks old): 4 animals in the vehicle group, 4 animals each in the NOV202 group, olaparib group, and the combination group of NOV202 and olaparib. only animals. NOV202 was synthesized as described in WO2012 / 127032. Olaparib was purchased from LC Laboratories. Patient-derived xenograft Ov10584 was used at passage number 7. On day 0, all mice received 2x2mm tissue fragments subcutaneously and tumors were allowed to reach 118mm before starting treatment 3 (average) palpable size (study day 8). The NOV202 group was administered PO at a dose of 30 mg / kg, and the olaparib group was administered PO at a dose of 100 mg / kg. The combination arm of NOV202 and olaparib has the same dose and schedule as monotherapy. NOV202 (5ml / kg) was administered in the morning and olaparib (10ml / kg) in the...

Embodiment 2

[0205] Antitumor Efficacy of NOV202 in Combination with Olaparib and Combination of Plinabulin and Olaparib in Patient-Derived Ovarian Cancer Xenografts (Ov10584)

[0206] NMRI was used as follows: nu / nu female (Janvier) mice (8 weeks old): 4 animals in the vehicle group, in the NOV202, olaparib, plinabulin, NOV202 and olaparib groups There were 4 animals in the combination group of Plinabulin and Olaparib respectively. NOV202 was synthesized as described in WO 2012 / 127032. Olaparib was purchased from LC Laboratories and Plinabulin was purchased from Sellechem. Patient-derived xenograft Ov10584 was used at passage number 4. On day 0, all mice received 2x2mm tissue fragments subcutaneously into the left flank, and tumors were allowed to reach 108mm before starting treatment 3 (average) palpable size (study day 6). The NOV202 group was administered PO at a dose of 30 mg / kg, and the olaparib group was administered PO at a dose of 100 mg / kg, and Plinabulin was administered int...

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Abstract

Methods and combination therapies for treating, preventing, and / or delaying the onset and / or development of cancer using a tubulin polymerization inhibitor such as a compound of formula I, or a pharmaceutically acceptable salt thereof, and a poly (ADP-ribose) polymerase (PARP) inhibitor,or a pharmaceutically acceptable salt thereof, are provided.

Description

technical field [0001] Provided are methods and combination therapies for treating, preventing and / or delaying the onset and / or progression of cancer, using a compound of formula I or a pharmaceutically acceptable salt thereof and poly (ADP-ribose) polymerase (PARP) Inhibitors or pharmaceutically acceptable salts thereof. Background technique [0002] Cancer is a phrase used to describe a wide variety of diseases, each characterized by the uncontrolled growth of a particular type of cell. It begins in tissue that contains these cells and can be treated with, for example, surgery, radiation, or another type of local therapy if the cancer has not spread to any other tissue at the time of diagnosis. However, when there is evidence that the cancer has metastasized from its tissue of origin, different treatments are typically used. Indeed, since the extent of metastases cannot be determined with certainty, systemic treatment is usually employed when any signs of spread are dete...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/506A61K31/497A61P31/00
CPCA61K31/506A61K45/06A61K31/496A61K31/502A61P35/00A61K2300/00A61P35/04
Inventor M·赫格伯格S·雷恩马克
Owner NOVIGA RES
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