IP Library › Granted Patent US 12,465,648
Granted Patent B2
US 12,465,648 · App. 17/604,636 · Granted Nov 11, 2025

Heterobifunctional compounds as degraders of HPK1

Inventors: Jian Jin (New York, NY); Steven Burakoff (New York, NY); H. Umit Kaniskan (New York, NY); Sansana Sawasdikosol (New York, NY); He Chen (New York, NY); Joshua Brody (New York, NY); Nina Bhardwaj (New York, NY)
Assignee: Icahn School of Medicine at Mount Sinai
A61K47/55A61K39/3955A61K47/545A61P35/00C07D401/14C07D403/14C07D417/14C07D487/04
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Quick Facts
Patent No.
US 12,465,648
App. No.
17/604,636
Granted
Nov 11, 2025
Kind
B2
Abstract

Disclosed are Hematopoietic Progenitor Kinase 1 (HPK1) degradation/disruption compounds including a HPK1 ligand, a degradation/disruption tag and a linker, and methods for use of such compounds in the treatment of HPK1-mediated diseases.

Claims (18)

1. A bivalent compound comprising a hematopoietic progenitor kinase 1 (HPK1) ligand conjugated to a degradation/disruption tag, selected from the group consisting of:

2-(2,6-dioxopiperidin-3-yl)-5-((7-(4-(4-(5-(2-fluoro-6-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)phenyl)piperazin-1-yl)-7-oxoheptyl)amino)isoindoline-1,3-dione (HC90-46);

2-(2,6-dioxopiperidin-3-yl)-4-((3-(4-(4-(5-(2-fluoro-6-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)phenyl)piperazin-1-yl)-3-oxopropyl)amino)isoindoline-1,3-dione (HC90-50);

2-(2,6-dioxopiperidin-3-yl)-4-((4-(4-(4-(5-(2-fluoro-6-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)phenyl)piperazin-1-yl)-4-oxobutyl)amino)isoindoline-1,3-dione (HC90-51);

2-(2,6-dioxopiperidin-3-yl)-4-((5-(4-(4-(5-(2-fluoro-6-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)phenyl)piperazin-1-yl)-5-oxopentyl)amino)isoindoline-1,3-dione (HC90-52);

2-(2,6-dioxopiperidin-3-yl)-4-((6-(4-(4-(5-(2-fluoro-6-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)phenyl)piperazin-1-yl)-6-oxohexyl)amino)isoindoline-1,3-dione (HC90-53);

2-(2,6-dioxopiperidin-3-yl)-4-((7-(4-(4-(5-(2-fluoro-6-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)phenyl)piperazin-1-yl)-7-oxoheptyl)amino)isoindoline-1,3-dione (HC90-54);

N-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)ethyl)-2-(4-(4-(5-(2-fluoro-6-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)phenyl)piperazin-1-yl)acetamide (HC90-86);

N-(4-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)butyl)-2-(4-(4-(5-(2-fluoro-6-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)phenyl)piperazin-1-yl)acetamide (HC90-88);

N-(4-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)butyl)-2-(4-(4-(5-(2-fluoro-6-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)phenyl)piperazin-1-yl)acetamide (HC90-104);

2-(2,6-dioxopiperidin-3-yl)-4-((8-(4-(4-(5-(2-fluoro-6-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)phenyl)piperazin-1-yl)-8-oxooctyl)amino)isoindoline-1,3-dione (HC90-117);

and pharmaceutically acceptable salts thereof.

2. A method of treating an HPK1-mediated disease in a subject in need thereof, comprising:

administering to a subject having an HPKI-mediated disease, a bivalent compound according to claim 1 .

3. A method of treating cancer in a subject in need thereof, comprising:

administering to a subject having cancer,

a pharmaceutical composition including a bivalent compound according to claim 1 , and a pharmaceutically acceptable carrier, and

a pharmaceutical composition including a checkpoint inhibitor and a pharmaceutically acceptable carrier.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 7, 2026
From: JIN, JIAN; BURAKOFF, STEVEN; KANISKAN, H. UMIT; SAWASDIKOSOL, SANSANA; CHEN, HE; BRODY, JOSHUA; BHARDWAJ, NINA
To: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
Reel/Frame 073398/0213 →
Continuity (2)
Provisional Application 62843816 · May 6, 2019
Related Publication 20230022524A1 · Jan 26, 2023
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