Identification of GDC-1971 (RLY-1971), a SHP2 Inhibitor Designed for the Treatment of Solid Tumors

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• SHP2 phosphatase is crucial for RAS-MAPK signaling, a key pathway in cancer.
• SHP2 is an emerging therapeutic target for various cancers, including those with KRAS mutations.
• Allosteric inhibition of SHP2 offers a promising strategy to inactivate the enzyme.

Purpose of the Study:

• To identify and characterize GDC-1971, a novel SHP2 inhibitor.
• To evaluate the potential of GDC-1971 as a single agent and in combination therapy.
• To investigate GDC-1971 for treating KRAS G12C-mutated solid tumors.

Main Methods:

• Drug discovery and characterization of small molecules targeting SHP2.
• In vitro and in vivo studies to assess SHP2 inhibitory activity.
• Clinical trial evaluation of GDC-1971 in combination with divarasib for solid tumors.

Main Results:

• GDC-1971 (formerly RLY-1971) effectively inhibits SHP2.
• GDC-1971 demonstrates pharmacological potential as an allosteric inhibitor.
• GDC-1971 is currently in clinical trials for KRAS G12C-driven solid tumors.

Conclusions:

• GDC-1971 is a potent SHP2 inhibitor with therapeutic potential.
• SHP2 inhibition is a viable strategy for targeting RAS-driven cancers.
• Combination therapy with GDC-1971 and KRAS inhibitors shows promise for solid tumors.