IP Library Granted Patent US 12,569,486
Granted Patent B2
US 12,569,486 · App. 18/439,926 · Granted Mar 10, 2026

Calmodulin inhibitors, CHK2 inhibitors and RSK inhibitors for the treatment of ribosomal disorders and ribosomapathies

Inventors: James Bradner (Weston, MA); Jun Qi (Sharon, MA); Dennis Buckley (Cambridge, MA); Leonard I. Zon (Brookline, MA); Elizabeth Macari (Wilmington, MA)
Assignees: THE CHILDREN'S MEDICAL CENTER CORPORATION; DANA-FARBER CANCER INSTITUTE, INC.
A61K31/517A61K31/225A61K31/403A61K31/506A61K31/519A61K31/5415A61K31/55A61K31/7048A61P7/06A61K45/06
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Quick Facts
Patent No.
US 12,569,486
App. No.
18/439,926
Granted
Mar 10, 2026
Kind
B2
Abstract

The present invention relates to methods, compositions and kits for treatment of ribosomal disorders and ribosomopathies, e.g. Diamond Blackfan anemia (DBA). In some embodiments, the invention relates to the use of novel classes of compounds, i.e. inhibitors of RSK (p90S6K); inhibitors of p70S6K; and inhibitors of rps6, to treat ribosomal disorders and ribosomopathies. In some embodiments, the invention relates to the use of specific Chk2 inhibitors and to the use of specific phenothiazine derivatives to treat ribosomal disorders and ribosomopathies, e.g. DBA.

Claims (10)

1 . A method of treating a subject with Diamond Blackfan Anemia (DBA), comprising administering an effective amount of a composition comprising an inhibitor of ribosomal s6 kinase, RSK (p90S6k), to the subject to decrease p90S6k activity and decrease active p53 in at least one of CD34+ cells, erythroid cells or erythroid differentiated cells in the subject, wherein

(i) the inhibitor of p90S6k is SL0101 (SL) and has the following structure:

 or

(ii) the inhibitor of p90S6k is BI-D1870 (BI) and has the following structure

2 . The method of claim 1 , wherein:

the inhibitor of p90S6k is SL0101.

3 . The method of claim 1 , wherein the subject has DBA1, DBA2, DBA3, DBA4, DBA5, DBA6, DBA7, or DBA8.

4 . The method of claim 1 , wherein the subject as a mutation in ribosomal protein 19 (RPS19).

5 . The method of claim 1 , wherein the subject is administered another therapeutic agent to treat the ribosomal protein defect, selected from corticosteroids and blood transfusions.

6 . The method of claim 1 , wherein the inhibitor of p90S6k is BI-D1870 (BI).

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 19, 2024
From: BRADNER, JAMES; QI, JUN; BUCKLEY, DENNIS
To: DANA-FARBER CANCER INSTITUTE, INC.
Reel/Frame 069315/0768 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 19, 2024
From: ZON, LEONARD I.; MACARI, ELIZABETH
To: CHILDREN'S MEDICAL CENTER CORPORATION, THE
Reel/Frame 069315/0889 →
CONFIRMATORY LICENSE Recorded Nov 19, 2024
From: BOSTON CHILDREN'S HOSPITAL
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 069397/0577 →
Continuity (4)
Division 17175079 · Feb 12, 2021
Continuation 16315899
Provisional Application 62361631 · Jul 13, 2016
Related Publication 20240342173A1 · Oct 17, 2024
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