NTX-1955
| Clinical data | |
|---|---|
| Other names | NTX1955; RO-7308480; RO7308480 |
| Routes of administration | Oral[1][2] |
| Drug class | γ1 subunit-containing GABAA receptor positive allosteric modulator |
NTX-1955, also known as RO-7308480, is a selective γ1 subunit-containing GABAA receptor positive allosteric modulator which is under development for the treatment of generalized anxiety disorder.[1][3][2][4][5] It is taken orally.[1][2]
Classical benzodiazepines are GABAA receptor positive allosteric modulators that act mainly upon γ2 subunit-containing GABAA receptors.[6][5] GABAA receptor γ2 subunits are the most abundantly expressed GABAA receptor subunits in the brain and are present in at least 90% of all GABAA receptors in the forebrain.[6] Moreover, they show high expression in the amygdala and have been extensively implicated in suppressing anxiety via actions in this area.[6][7] Conversely, NTX-1955 is a selective positive allosteric modulator of γ1 subunit-containing GABAA receptors.[4][5] Though γ2 subunit-containing GABAA receptors are dominant in this area,[6][7] γ1 subunit-containing GABAA receptors are also highly expressed in the central amygdala, and selective positive allosteric modulators of these receptors have been found to produce anxiolytic-like effects without side effects like sedation and cognitive and motor impairment in animals.[5][8] As such, it is thought that selectivity for γ1 subunit-containing GABAA receptors may confer improved tolerability compared to existing drugs like benzodiazepines.[4][5] Due to its novel mechanism of action, NTX-1955 is a potential first-in-class medication.[4][5]
NTX-1955 was originated by Roche and is under development by Newleos Therapeutics.[1][3] As of April 2026, it is in phase 1 clinical trials for generalized anxiety disorder, with several phase 1 trials having been completed.[1][3][4] There was also interest in NTX-1955 for potential treatment of social anxiety disorder.[4] The chemical structure of NTX-1955 does not yet appear to have been disclosed, but it is said to be structurally related to benzodiazepines.[9]
See also
[edit]References
[edit]- 1 2 3 4 5 "NTX 1955". AdisInsight. 15 April 2026. Retrieved 6 June 2026.
- 1 2 3 "NTX-1955 Drug Profile". Ozmosi. 1 January 1900. Retrieved 6 June 2026.
- 1 2 3 "Delving into the Latest Updates on RO-7308480 with Synapse". Synapse. 30 May 2026. Retrieved 6 June 2026.
- 1 2 3 4 5 6 Masson, Gabrielle (13 February 2025). "VC Longwood Fund unveils neuro biotech with $93M, assets licensed from Roche". Fierce Biotech. Retrieved 6 June 2026.
- 1 2 3 4 5 6 Maria-Clemencia Hernandez (10 September 2025). A Novel Approach for Anxiety Treatment: Discovery of Selective GABAA γ1 Positive Allosteric Modulators for Targeted Modulation of Extended Amygdala Circuits (PDF). 17th World Congress of Biological Psychiatry (WCBP), September 9-12, Berlin, Germany.
- 1 2 3 4 Babaev O, Piletti Chatain C, Krueger-Burg D (April 2018). "Inhibition in the amygdala anxiety circuitry". Exp Mol Med. 50 (4): 1–16. doi:10.1038/s12276-018-0063-8. PMC 5938054. PMID 29628509.
The most abundant GABAAR subunit in the CNS is the γ2-subunit, which is estimated to be present in at least 90% of all GABAARs in the forebrain4,83. The γ2-subunit is highly expressed throughout the amygdala of rodents84 and humans85, and several lines of evidence support a key role for γ2-GABAARs in the anxiety circuitry (see also Table 2). First, benzodiazepines bind to the interface between the α- and γ-subunits, and only γ2-containing GABAARs (γ2-GABAARs) are sensitive to classical benzodiazepines4. [...]
- 1 2 Song JJ, Curtis MA, Faull RL, Waldvogel HJ (December 2022). "The regional and cellular distribution of GABAA receptor subunits in the human amygdala". J Chem Neuroanat. 126 102185. doi:10.1016/j.jchemneu.2022.102185. PMID 36374781.
- ↑ Esmaeili A, Lynch JW, Sah P (January 2009). "GABAA receptors containing gamma1 subunits contribute to inhibitory transmission in the central amygdala". J Neurophysiol. 101 (1): 341–349. doi:10.1152/jn.90991.2008. PMID 19004994.
- ↑ https://www.oryzon.com/sites/default/files/documents/2025-02/INVEST%20SECURITIES%20-%20FLASH%20ORYZON%20GENOMICS%20-%2020250221_EN.pdf "NTX-1955 is a selective GABAA-γ1 positive allosteric modulator for the treatment of generalized anxiety disorder. Its structure is related to benzodiazepines but has the advantage of targeting only a specific GABA receptor subunit found in the amygdala and not in the brain. This selectivity helps avoid the adverse effects typically associated with benzodiazepines, such as safety concerns and potential for abuse."