METTL14 modulators(methyltransferase 14, N6-adenosine-methyltransferase subunit modulators), METTL3 modulators(methyltransferase 3, N6-adenosine-methyltransferase complex catalytic subunit modulators)

Therapeutic Areas

NeoplasmsHemic and Lymphatic Diseases

Active Indication

Acute Myeloid Leukemia

Inactive Indication-

Originator Organization

Canthera Discovery Ltd

Active Organization

Canthera Discovery Ltd

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Structure

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100 Clinical Results associated with METTL3/14 modulators(Canthera Discovery)

100 Translational Medicine associated with METTL3/14 modulators(Canthera Discovery)

100 Patents (Medical) associated with METTL3/14 modulators(Canthera Discovery)

Literatures (Medical) associated with METTL3/14 modulators(Canthera Discovery)

Acta Neuropsychiatrica

RNA m⁶A methyltransferase activator affects anxiety-related behaviours, monoamines and striatal gene expression in the rat

Article

Author: Org, Tõnis ; Liiver, Kristi ; Norden, Marianna ; Shimmo, Ruth ; Teino, Indrek ; Harro, Jaanus ; Saarma, Mart ; Laugus, Karita ; Kanarik, Margus ; Karelson, Mati

AbstractModification of mRNA by methylation is involved in post-transcriptional regulation of gene expression by affecting the splicing, transport, stability and translation of mRNA. Methylation of adenosine at N6 (m6A) is one of the most common and important cellular modiﬁcation occurring in the mRNA of eukaryotes. Evidence that m6A mRNA methylation is involved in regulation of stress response and that its dysregulation may contribute to the pathogenesis of neuropsychiatric disorders is accumulating. We have examined the acute and subchronic (up to 18 days once per day intraperitoneally) effect of the first METTL3/METTL14 activator compound CHMA1004 (methyl-piperazine-2-carboxylate) at two doses (1 and 5 mg/kg) in male and female rats. CHMA1004 had a locomotor activating and anxiolytic-like profile in open field and elevated zero-maze tests. In female rats sucrose consumption and swimming in Porsolt’s test were increased. Nevertheless, CHMA1004 did not exhibit strong psychostimulant-like properties: CHMA1004 had no effect on 50-kHz ultrasonic vocalizations except that it reduced the baseline difference between male and female animals, and acute drug treatment had no effect on extracellular dopamine levels in striatum. Subchronic CHMA1004 altered ex vivo catecholamine levels in several brain regions. RNA sequencing of female rat striata after subchronic CHMA1004 treatment revealed changes in the expression of a number of genes linked to dopamine neuron viability, neurodegeneration, depression, anxiety and stress response. Conclusively, the first-in-class METTL3/METTL14 activator compound CHMA1004 increased locomotor activity and elicited anxiolytic-like effects after systemic administration, demonstrating that pharmacological activation of RNA m6A methylation has potential for neuropsychiatric drug development.

100 Deals associated with METTL3/14 modulators(Canthera Discovery)

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Acute Myeloid Leukemia	Preclinical	AU	Canthera Discovery Ltd	-

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METTL3/14 modulators(Canthera Discovery)

Overview

Basic Info

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R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation