US 2025/0082652 A1 · SIGNALLING-PATHWAY INHIBITOR COMBINATIONS FOR USE IN THE TREATMENT OF CANCER DISEASES

Abstract

The present invention pertains to the treatment of proliferative diseases, such as cancer. In particular, the invention describes a novel combination therapy strategy, comprising a Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) inhibitor, an Inhibitor of κB (IκB) Kinase (IKK)/Nuclear Factor κB (NFκB)-signaling inhibitor, and a B-cell lymphoma 2 (BCL-2) inhibitor for the treatment and/or prevention of proliferative diseases, such as cancer. The invention provides such inhibitory compounds and their combinations for use in medical applications, as well as pharmaceutical compositions comprising the compounds of the invention. The invention further pertains to a method of treatment and/or prevention of a proliferative disease in a subject, the method comprising administering to the subject as single treatments or one or more combinatorial treatments, either sequentially or concomitantly, a therapeutically effective amount of inhibitors of RIPK1, inhibitors of IKK/NFκB-signalling, and inhibitors of BCL-2.

Claims23

Dependent claims

A method of treatment and/or prevention of a proliferative disorder in a subject, the method comprising a step of administering a compound to the subject, wherein the compound is selected from:

(i) A Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) inhibitor;
(ii) An Inhibitor of κKB (IκB) Kinase (IKK)/Nuclear Factor κB (NFκB)-signalling inhibitor;
and
(iii) A B-cell lymphoma 2 (BCL-2) inhibitor,
wherein if the compound is (a), the subject will receive, receives or has received an additional treatment with (b) and (c), or if the compound is (b), the subject will receive, receives or has received an additional treatment with (a) and (c), or if the compound is (c), the subject will receive, receives or has received an additional treatment with (a) and (b).

2 more elements

A method for the identification of a therapeutic combination of candidate molecules that reduces viability of cells involved with, or associated with, a proliferative disorder, the method comprising the steps of

(i) Providing a test cell involved or associated with the proliferative disorder,
(ii) Contacting the test cell with a combination of a first candidate inhibitory molecule targeting IKK1, concomitantly contacting the test cell with a second candidate inhibitory molecule targeting Bcl-2, and concomitantly contacting the test cell with a third candidate inhibitory molecule targeting RIPK1;
(iii) Optionally, providing a control cell which corresponds to the test cell, but is not contacted with one or more of the first candidate inhibitory molecule, the second candidate inhibitory molecule, or the third candidate inhibitory molecule;
(iv) Determining viability and/or proliferation of the test cell, optionally the control cell, subsequently;
Wherein a reduced, preferably synergistically reduced, viability of the test cell, optionally compared to the control cell, indicates that the combination of the first candidate inhibitory molecule, the second candidate inhibitory molecule, and the third candidate inhibitory molecule, is a combination of molecules that reduces viability of cells involved with, or associated with, a proliferative disorder.

2 more elements

Dependencies are inferred from the claim text.

Signalling-pathway inhibitor combinations for use in the treatment of cancer diseases

Life of this patent

Signalling-pathway inhibitor combinations for use in the treatment of cancer diseases

Life of this patent

Abstract

Claims23