Innovative Drug Discovery: Targeting Cancer, Neurological Disorders, and Obesity

Abstract

The landscape of therapeutic innovation is rapidly evolving, with significant advances in cancer treatment, obesity management, and the modulation of protein interactions in neurodegenerative disorders. This Patent Highlight explores the scientific breakthroughs described in four recent patents covering novel therapeutic compounds, advanced methods for identifying E3 ligase substrates, and developing new strategies for combating obesity and its related metabolic disorders. These innovations, focusing on specific molecular targets and pathways, promise more effective and personalized treatment options, addressing unmet needs in oncology, neurology, and metabolic health.

Important Compound Classes

Titles

Diacylglycerol Acyl Transferase 2 Inhibitors; Systems, Compositions and Methods for identifying E3 Ligase Substrates by Ubiquitin Biotinylation; Bicyclic-Substituted Glutarimide Cereblon Binders; and Solid Forms of a Thienopyrimidinedione ACC Inhibitor and Methods for Production Thereof

Patent Publication Numbers

US 2024/0140937 A1 (URL: https://patents.google.com/patent/US20240140937A1/en?oq=US+2024%2f0140937+A1);

WO 2023/235313 A2 (URL: https://patents.google.com/patent/WO2023235313A2/en?oq=WO+2023%2f235313+A2);

WO 2023/239750 A1 (URL: https://patents.google.com/patent/WO2023239750A1/en?oq=WO+2023%2f239750+A1); and

EP 4364795 A2 (URL: https://patents.google.com/patent/EP4364795A2/en?oq=EP+4364795+A2)

Publication Dates

May 2, 2024; December 7, 2023; December 14, 2023; August 5, 2024

Priority Applications

US 18/520,638; US 63/347,802; US 63/349,509; US 201662303237 P

Priority Dates

November 28, 2023; June 1, 2022; June 6, 2022; March 3, 2016

Inventors

Boehm, M.; Cabral, S.; Dowling, M. S.; Yin Lee, E. C.; Polivkova, J.; Price, D. A.; Li, Q. (US 2024/0140937 A1); Sellers, W.; Huang, H. (WO 2023/235313 A2); Nasveschuk, C. G.; Lazarski, K.; Hird, A. W.; Yin, N.; Good, A. C.; Huang, H.; Eron, S. J.; Veits, G. K. (WO 2023/239750 A1); and Patent EP 4364795 A2 lists a pending inventor designation.

Assignee Companies

Pfizer Inc., New York, NY (US) (US 2024/0140937 A1); The Broad Institute, Inc. [US/US], 415 Main Street, Cambridge, Massachusetts 02142 (US); Dana-Farber Cancer Institute, Inc. [US/US], 450 Brookline Avenue, Boston, Massachusetts 02215 (US) (WO 2023/235313 A2); C4 Therapeutics, Inc., [US/US], 490 Arsenal Way, Suite 120, Watertown, MA 02472 (US) (WO 2023/239750 A1); Gilead Apollo, LLC, Foster City, CA 97704 (US) (EP 4364795 A2)

Disease Area

Cancer, neurological disorders, obesity, and metabolic disorders

Biological Targets

Kinase and signaling pathways in cancer, E3 ligases in protein homeostasis and protein–protein interactions

Summary

In recent years, the need for novel therapeutic strategies has become increasingly urgent as traditional treatments face limitations in efficacy, safety, and patient outcomes. This Patent Highlight reviews four important patents representing cutting-edge developments in drug discovery and therapeutic approaches across various medical fields, including cancer, obesity, and neurodegenerative diseases.

Targeting Key Proteins and Pathways in Cancer Therapy. Cancer remains a leading cause of mortality worldwide, driving ongoing research into more effective treatments. The patent application US 20240140937 A1 introduces a new class of compounds designed to target specific proteins or pathways essential for cancer cell survival. These compounds act as inhibitors of kinases or other critical molecules in the signaling pathways that regulate tumor growth and proliferation. By disrupting these pathways, these compounds offer the potential for halting disease progression, particularly in cancers resistant to existing therapies.

The innovation described in this patent application highlights the importance of personalized medicine, where treatments are tailored based on the genetic and molecular profile of a patient’s tumor. This approach could significantly enhance the effectiveness of cancer therapies, offering hope for improved patient outcomes in the face of challenging and aggressive cancers.

Neurological Disorders and Protein Modulation. The patent application WO 2023/235313 A2 focuses on identifying substrates of E3 ligases, enzymes that play a crucial role in cellular protein homeostasis through ubiquitination. This process is particularly relevant in diseases such as cancer and neurological disorders, where protein misfolding and degradation can lead to pathogenesis.

The method described in the patent application involves the biotinylation of ubiquitinated substrates by a biotin ligase fused to an E3 ligase. This innovative technique allows for the specific and efficient identification of substrates, overcoming previous limitations such as low throughput and bias. The ability to isolate and study these substrates provides valuable insights into the role of ubiquitination in disease mechanisms, paving the way for developing targeted therapies that can modulate protein homeostasis.

Bicyclic-Substituted Compounds in Disease Modulation. Another promising development is the introduction of bicyclic-substituted compounds as described in the patent application WO 2023239750 A1. These compounds represent a new class of therapeutics that can potentially treat various diseases, including cancer and neurodegenerative disorders. These compounds modulate protein–protein interactions or enzyme activities, which are crucial in cellular signaling and disease progression.

Preclinical studies have shown that these bicyclic-substituted compounds can effectively modulate the activity of target proteins, offering a novel approach to therapy. The patent application also discusses strategies to optimize these compounds for better pharmacokinetic properties, such as increased bioavailability and stability, enhancing their therapeutic potential.

A New Frontier in Obesity and Metabolic Disorders. Obesity has become a global health crisis with significant implications for public health and healthcare systems. The patent application EP 4364795 A2 addresses the urgent need for new therapeutic options to combat obesity and its related metabolic disorders. Despite the availability of current pharmacotherapies, sustainable weight loss remains a challenge, highlighting the need for innovative approaches.

This patent application introduces a novel compound, Compound 1, designed to target metabolic pathways involved in obesity and diabetes management. The compound’s unique structure allows it to be formulated in various crystalline forms, enhancing its therapeutic efficacy. Additionally, the patent outlines the potential for combining Compound 1 with other antidiabetic or antiobesity agents to create more comprehensive treatment regimens.

As such, the patents discussed in this Patent Highlight represent promising advancements in therapeutic innovation, offering new hope for treating complex diseases such as cancer, obesity, and neurodegenerative disorders. By targeting specific proteins, pathways, and cellular processes, these innovations pave the way for more effective, personalized, and safer treatment options. As these technologies continue to develop, they hold the potential to transform the landscape of medical treatment, addressing unmet needs and improving patient outcomes across a range of challenging health conditions.

Key Structures

Biological Assay

Bicyclic-substituted compounds were tested withi both in vitro biochemical assays and in vivo studies. The in vitro assays focus on interactions between the compounds and their protein targets. In contrast, the in vivo assays in animal models assess the overall efficacy of these compounds in disease contexts, such as cancer and neurodegenerative disorders.

Biological Data

The table shows benzomorpholine CRBN binders, where *** = ≤1 μM; ** = ≤100 μM.

Recent Review Articles

See refs (1−6).

The author declares no competing financial interest.