STING agonistic compound
Inventors
HANADA, Ryosuke • Kokubo, Masaya • KURONO, Masakuni • KOUDA, Kenichi • Hagiya, Hiroshi
Assignees
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Publication Number
US-12152049-B2
Publication Date
2024-11-26
Expiration Date
Abstract
A drug or agent containing a compound having an agonistic activity to STING as an active ingredient, where the compound is represented by the following general formula (I-1): wherein all symbols represent the same meanings as described in the specification, and the compound can be used as an active ingredient of an agent for suppressing the progression of, suppressing the recurrence of and/or treating cancer or infectious disease.
Core Innovation
The invention provides small-molecule compounds as active ingredients, including compounds of general formula (I) and (I-1), and also presents specific phosphonooxyalkyl and phosphate forms associated with the compounds. The described embodiments include N-oxides, prodrugs, pharmaceutically acceptable salts, and solvates, including hydrates, with heterocycle-based scaffold parameters such as Ring A, Ring B, linkers L1 and L2, substituents X, Y, Z, T, and residue groups R1-R7.
The problem addressed is cancer progression and/or recurrence and the need to treat cancer and infectious disease, in relation to innate immunity and activation of the STING pathway. The rationale described is that STING pathway activation occurs via cGAS/cGAMP and cyclic dinucleotides and can involve the endoplasmic reticulum, leading to type I interferon responses, and the document frames its novelty as a structure not previously reported in the context of STING agonism.
The compounds are positioned as STING-agonistic small-molecule drugs. The document states that STING agonism enables use for cancer and infectious disease agents by administering the compounds, including pharmaceutically acceptable salts or solvates, as active ingredients to a subject for the stated therapeutic purposes.
Claims Coverage
Two independent claims are identified. Each independent claim centers on administering an effective amount of a specific small-molecule, including pharmaceutically acceptable salts or solvates, with either a cancer therapeutic purpose or a STING stimulation purpose.
Administering a specific dihydrogen phosphate compound to suppress cancer progression, recurrence, or treat cancer
A method for suppressing the progression of, suppressing the recurrence of, or treating cancer in a subject in need thereof, comprising administering an effective amount of (4-(4-(5-acetyl-4-amino-2-fluorophenyl)-3-aminoisoxazolo[4,5-c]pyridin-7-yl)-1H-pyrazol-1-yl)methyl dihydrogen phosphate, a pharmaceutically acceptable salt thereof or a solvate thereof.
Administering a specific dihydrogen phosphate compound to stimulate STING
A method for stimulating STING (Stimulation of Interferon Genes) in a subject in need thereof, comprising administering an effective amount of (4-(4-(5-acetyl-4-amino-2-fluorophenyl)-3-aminoisoxazolo[4,5-c]pyridin-7-yl)-1H-pyrazol-1-yl)methyl dihydrogen phosphate, a pharmaceutically acceptable salt thereof or a solvate thereof.
The claim set covers methods based on administering the same specific small-molecule dihydrogen phosphate, or a pharmaceutically acceptable salt or solvate, either to suppress cancer progression or recurrence and treat cancer, or to stimulate STING in a subject in need thereof.
Stated Advantages
Suppressing the progression of, suppressing the recurrence of, or treating cancer in a subject.
Stimulating STING (Stimulation of Interferon Genes) in a subject.
STING agonism enables use in cancer and infectious disease agents.
Documented Applications
STING/IRF pathway activation in THP1-Dual cells and THP1-Dual-STING KO cells, with downstream in vitro IDO1 inhibitory activity and kinase inhibition panel results.
In vivo MC38 subcutaneous colon tumor growth suppression.
Pharmaceutical solvates and salts characterization for the specified phosphate-bearing compound, including acetate or acetic acid solvate, hydrate, and monopotassium salt.
Suppressing the progression of, suppressing the recurrence of, or treating cancer in a subject in need thereof.
Stimulating STING (Stimulation of Interferon Genes) in a subject in need thereof.
Infectious disease applications, including viral infections, parasitic infections, bacterial infections, and fungal infections.
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