SOS1 inhibitors
Inventors
Marx, Matthew Arnold • Ketcham, John Michael • Smith, Christopher Ronald • Lawson, John David • BURNS, Aaron Craig • Wang, Xiaolun • Kulyk, Svitlana • Ivetac, Anthony
Assignees
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Publication Number
US-12304915-B2
Publication Date
2025-05-20
Expiration Date
Abstract
The present invention relates to methods of treating cancer using compounds that inhibit Son of sevenless homolog 1 (SOS1) activity and pharmaceutical compositions containing such compounds.
Core Innovation
The invention relates to compounds of Formula (I) and pharmaceutically acceptable salts thereof for inhibiting SOS1 activity in a cell. The methods comprise contacting a cell with an effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt thereof, and the compound of Formula (I) is defined by variable substituents and ring selections including R1, R2 and L-R2, Q, X, R3, Y, R4, R5, L, R6, R8, R9, R10, R11, and R12.
The invention further provides methods for treating cancer by administering to a patient having cancer a therapeutically effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt thereof. The cancer is limited to Ras family-associated cancer, SOS1-associated cancer, or NF-1/NF-2 associated cancer, and the treatment can be provided alone or combined with a pharmaceutically acceptable carrier, excipient or diluents.
The document describes representative Formula (I) compounds and characterizes examples by 1H NMR and LCMS data, including salt forms such as hydrochloride, formate, and dihydrochloride salts. The examples include phthalazin-1-amine and pyrido[3,4-d]pyridazin-1-amine core motifs with varied substituents and stereochemistry, consistent with the disclosed Formula (I) compound class.
Claims Coverage
The consolidated claim coverage includes three main independent method groups: inhibiting SOS1 activity in a cell, treating cancer by administering a Formula (I) compound, and treating cancer by administering a pharmaceutically acceptable salt of a Formula (I) compound. Across the independent claims, the core inventive features center on compounds of Formula (I) or salts thereof, with cancer indications limited to Ras family-associated, SOS1-associated, or NF-1/NF-2 associated cancers.
Contacting a cell with a formula i compound to inhibit sos1 activity
A method for inhibiting SOS1 activity in a cell by contacting the cell with an effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt thereof.
Treating cancer by administering a formula i compound
A method for treating cancer comprising administering to a patient having cancer a therapeutically effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt thereof, wherein the cancer is a Ras family-associated cancer, a SOS1-associated cancer or a NF-1/NF-2 associated cancer.
Treating cancer with a pharmaceutically acceptable salt of a formula i compound
A method for treating cancer comprising administering to a patient having cancer a therapeutically effective amount of a pharmaceutically acceptable salt of a compound of the following formula, alone or combined with a pharmaceutically acceptable carrier, excipient or diluents, wherein the cancer is a Ras family-associated cancer, a SOS1-associated cancer or a NF-1/NF-2 associated cancer.
The independent claims collectively cover SOS1 inhibition by contacting cells with Formula (I) compounds or salts, and cancer treatment by administering Formula (I) compounds or pharmaceutically acceptable salts, with the cancer scope limited to Ras family-associated, SOS1-associated, or NF-1/NF-2 associated cancers.
Stated Advantages
Inhibits SOS1 activity.
Prevents Ras activation by targeting SOS1.
Treats cancer in patients whose tumors are Ras family-associated, SOS1-associated, or NF-1/NF-2-associated.
Cancer treatment by administering therapeutically effective amounts of Formula (I) compounds or pharmaceutically acceptable salts.
Documented Applications
Inhibiting SOS1 activity in a cell by contacting the cell with Formula (I) compounds or pharmaceutically acceptable salts.
Treating cancer by administering Formula (I) compounds or pharmaceutically acceptable salts to patients with Ras family-associated, SOS1-associated, or NF-1/NF-2-associated cancers.
In vitro SOS1 binding and functional inhibition using HTRF tracer displacement assays, with IC50 and Ki values.
In-cell inhibition assessed by pERK pathway inhibition in KRAS/SOS1/NF-1 mutant cell lines.
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