KCNT1 inhibitors and methods of use
Inventors
MARTINEZ BOTELLA, Gabriel • Griffin, Andrew Mark
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11773088-B2
Publication Date
2023-10-03
Expiration Date
Abstract
The present invention is directed to, in part, compounds and compositions useful for preventing and/or treating a neurological disease or disorder, a disease or condition relating to excessive neuronal excitability, and/or a gain-of-function mutation in a gene (e.g., KCNT1). Methods of treating a neurological disease or disorder, a disease or condition relating to excessive neuronal excitability, and/or a gain-of-function mutation in a gene such as KCNT1 are also provided herein.
Core Innovation
The disclosed subject matter relates to KCNT1 (Slack), described as a sodium-activated potassium channel, whose abnormal activity and gain-of-function activity are linked to early-onset epilepsies and intellectual impairment. The document addresses neurological diseases and disorders involving excessive neuronal excitability and/or KCNT1 gain-of-function, and provides KCNT1 inhibitor compounds as solutions associated with these conditions.
The invention further discloses KCNT1 inhibitor compounds, represented by structural depictions, and pharmaceutical compositions containing the KCNT1 inhibitor compounds together with pharmaceutically acceptable salts and pharmaceutically acceptable excipients. The disclosures also encompass stereoisomers and isotopic substitutions, and include general definitions for pharmaceutically acceptable salts and related compound forms.
In addition, the document includes an assay framework summarizing evaluation of KCNT1 patch-clamp inhibition, including a Table 1 classification for compounds 1–8. The assay summary is presented in the context of whole-cell patch clamp inhibition for KCNT1 and provides an IC50-based classification approach.
Claims Coverage
The independent claim covers a compound selected from a specified group or a pharmaceutically acceptable salt thereof, and the related claim set refines coverage into pharmaceutical compositions and treatment methods that include multiple neurological condition classes. The extracted inventive features below reflect the main claim-level limitations described in the provided claim texts.
Selected group compound or pharmaceutically acceptable salt
A compound selected from the group consisting of [group members not reproduced in the excerpt] or a pharmaceutically acceptable salt thereof.
Pharmaceutical composition with excipient
A pharmaceutical composition comprising a compound selected from the group consisting of [group members not reproduced in the excerpt] (or a pharmaceutically acceptable salt thereof) and a pharmaceutically acceptable excipient.
Treatment method for neurological disease or disorder
A method for treating a neurological disease or disorder (including conditions associated with excessive neuronal excitability or a gain-of-function mutation) by administering a compound selected from the group consisting of [group members not reproduced in the excerpt] (or a pharmaceutically acceptable salt thereof).
Epilepsy-related neurological disease/encephalopathy
The neurological disease or disorder is epilepsy, an epilepsy syndrome, or an encephalopathy.
Seizure types constrained
The seizures are Generalized tonic clonic seizures, or Asymmetric Tonic Seizures.
Neurodevelopmental disorder targets
The neurological disease or condition associated with excessive neuronal excitability and/or a gain-of-function mutation in a gene is a learning disorder, Fragile X, neuronal plasticity, or an autism spectrum disorder.
Overall, the claim coverage is directed to KCNT1 inhibitor compounds and their pharmaceutically acceptable salts, with dependent coverage specifying formulation with a pharmaceutically acceptable excipient and therapeutic administration to neurological diseases. The therapeutic scope is further refined to epilepsy, epilepsy syndromes, encephalopathies, specific seizure phenotypes, and neurodevelopmental conditions including learning disorders, Fragile X, neuronal plasticity, and autism spectrum disorders.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
Interested in licensing this patent?