NBI-1076968

NBI-1076968
Clinical data
Other names	NBI1076968
Routes of; administration	Oral
Drug class	Muscarinic acetylcholine M4 receptor antagonist

NBI-1076968 is a selective muscarinic acetylcholine M₄ receptor antagonist which is under development by Neurocrine Biosciences for the treatment of movement disorders.^[1]^[2] It is orally active.^[1]^[2]

Pharmacology

Along with the earlier drugs PD-0298029 and PD-102,807, NBI-1076968 is among the only selective M₄ receptor antagonists to have been developed to date.^[3] However, in contrast to NBI-1076968, the earlier selective antagonists have not had optimal drug-like properties for development as pharmaceutical drugs.^[3]

Clinical trials

As of September 2024, NBI-1076968 is in phase 1 clinical trials for treatment of movement disorders.^[1] The drug is under development by Neurocrine Biosciences.^[1] It was first described in 2024.^[1]^[2]

References

^ ^a ^b ^c ^d ^e ^f ^g "NBI 1076968". AdisInsight. Springer Nature Switzerland AG. 11 September 2024. Retrieved 20 October 2024.
^ ^a ^b ^c ^d ^e Neurocrine Biosciences (1 August 2024). "Neurocrine Biosciences Reports Second Quarter 2024 Financial Results and Raises 2024 INGREZZA Sales Guidance". PR Newswire. Retrieved 20 October 2024. Initiated Phase 1 study of NBI-1076968 in healthy adult participants. NBI-1076968 is an investigational, oral, M4 subtype-selective muscarinic antagonist for the potential treatment of movement disorders.
^ ^a ^b Weinhart CG (18 February 2021). Synthesis and pharmacological characterization of dibenzodiazepinone-type muscarinic M2-receptor antagonists conjugated to fluorescent dyes or small peptides (Ph.D. thesis). University of Regensburg. Retrieved 20 October 2024. On the other hand, also the development of selective M4R antagonists, which were suggested to restore the dopamine acetylcholine balance in patients with PD, has been challenging.133 To date, only PD-102807, PD-0298029 and a few other benzoxazine analogues were described (Figure 1.7).131 The former is still used in scientific research for studying the effects of the different MR subtypes in the brain and in the periphery.134-136 PD0298029 exhibited poor bioavailability and rapid metabolism in animal studies, which limits its use to in vitro studies.137 In summary, selective M4R ligands, representing drug candidates, e.g. for the treatment of AD, SZ or PD, are not available to date.

[AdisInsight-1] ^ ^a ^b ^c ^d ^e ^f ^g "NBI 1076968". AdisInsight. Springer Nature Switzerland AG. 11 September 2024. Retrieved 20 October 2024.

[PRNewswire2024-2] Neurocrine Biosciences (1 August 2024). "Neurocrine Biosciences Reports Second Quarter 2024 Financial Results and Raises 2024 INGREZZA Sales Guidance". PR Newswire. Retrieved 20 October 2024. Initiated Phase 1 study of NBI-1076968 in healthy adult participants. NBI-1076968 is an investigational, oral, M4 subtype-selective muscarinic antagonist for the potential treatment of movement disorders.

[Weinhart2021-3] Weinhart CG (18 February 2021). Synthesis and pharmacological characterization of dibenzodiazepinone-type muscarinic M2-receptor antagonists conjugated to fluorescent dyes or small peptides (Ph.D. thesis). University of Regensburg. Retrieved 20 October 2024. On the other hand, also the development of selective M4R antagonists, which were suggested to restore the dopamine acetylcholine balance in patients with PD, has been challenging.133 To date, only PD-102807, PD-0298029 and a few other benzoxazine analogues were described (Figure 1.7).131 The former is still used in scientific research for studying the effects of the different MR subtypes in the brain and in the periphery.134-136 PD0298029 exhibited poor bioavailability and rapid metabolism in animal studies, which limits its use to in vitro studies.137 In summary, selective M4R ligands, representing drug candidates, e.g. for the treatment of AD, SZ or PD, are not available to date.

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