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Combinations of AHR inhibitor and PD1 inhibitor antibodies and their use in treatment of cancer

An inhibitor, solvate technology, applied in the treatment or prevention of disease, PD-1 inhibitor, treatment or prevention of cancer in a subject, the field of drugs for the treatment of cancer or tumor, can solve the problem that the curative effect is not sustainable, Disease recurrence, etc.

Pending Publication Date: 2022-07-22
BAYER AG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0027] However, despite the great success of the above-identified approaches, it turns out that the efficacy of some of them is not sustainable, i.e. disease recurrence occurs, and / or they are only effective in certain types of cancer

Method used

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  • Combinations of AHR inhibitor and PD1 inhibitor antibodies and their use in treatment of cancer
  • Combinations of AHR inhibitor and PD1 inhibitor antibodies and their use in treatment of cancer
  • Combinations of AHR inhibitor and PD1 inhibitor antibodies and their use in treatment of cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 17

[1389] It is 6-(4-chlorophenyl)-N-[(2S)-1-hydroxypropan-2-yl]-2-(1-methyl-1H-pyrazol-4-yl)-3-oxo Substituted-2,3-dihydropyridazine-4-carboxamide, the structure is:

[1390]

[1391] or its polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, and their physiologically acceptable Salts and solvates of such salts, and mixtures thereof.

[1392] Component B:

[1393] Component B is either pembrolizumab or nivolumab.

[1394] mixed lymphocyte reaction

[1395] Whole blood samples from healthy donors were collected and PBMCs were isolated using density gradient centrifugation at 800 xg for 15 minutes at room temperature with Biocoll separator (density 1.977 g / mL; Biochrom, #L6115). Discard the supernatant and pour the PBMC into a 50 mL tube with Ca-free + / Mg + were washed with PBS, counted and resuspended in MACS separation buffer (Miltenyi Biotec). Monocytes were isolated from PBMCs using Monocyte Isolation Kit II (miltenyi biote...

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Abstract

The present invention relates to a combination of at least two components, component A and component B, component A being an AhR inhibitor and component B being pemmumab or Nasumab. Another aspect of the invention relates to a combination of three components, component A, component B and component C; the component A is an AhR inhibitor, the component B is pemmumab or Nasumab, and the component C is another agent. The invention further relates to the use of such a combination as described herein for the preparation of a medicament for the treatment or prophylaxis of a disease, the compounds are useful in the treatment or prevention of breast cancer, respiratory tract cancer, brain cancer, reproductive organ cancer, digestive tract cancer, urinary tract cancer, eye cancer, liver cancer, skin cancer, kidney cancer, head and neck cancer, thyroid cancer, parathyroid cancer, and their distal metastases, lymphoma, sarcoma and leukemia.

Description

[0001] The present invention relates to the combination of at least two components (component A and component B), component A being an aryl hydrocarbon receptor (AhR) inhibitor, and component B being a PD-1 inhibitor. [0002] The term "aryl hydrocarbon receptor inhibitor" is abbreviated hereinafter as "AhR inhibitor". [0003] Another aspect of the present invention relates to the use of such a combination as described herein as a medicament for the treatment or prophylaxis of a disease, in particular for the treatment of cancer or tumors; to the use of such a combination as described herein in the manufacture of a treatment Or the use of a drug for the prevention of disease, especially for the treatment of cancer or tumors. [0004] Another aspect of the invention relates to a method of treating or preventing cancer in a subject comprising administering to the subject a therapeutically effective amount of a combination as described herein. [0005] In addition, the present in...

Claims

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Application Information

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IPC IPC(8): A61K31/501A61K31/506A61K39/395A61P35/00
CPCA61K31/501A61K31/506A61K39/3955A61P35/00C07K16/2818C07K2317/21C07K2317/76C07K2317/70C07K2317/73A61K39/39541C07K2317/24A61K2300/00A61K31/381C07K16/2827
Inventor I·古彻
Owner BAYER AG
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