Onametostat (JNJ-64619178)

Onametostat (JNJ-64619178) is a PRMT5 inhibitor with high selectivity and potency (subnanomolar range, PRMT5-MEP-50 IC50=0.14 nM) under different in vitro and cellular conditions, paired with favorable pharmacokinetics and safety properties.

Onametostat (JNJ-64619178) Chemical Structure

Onametostat (JNJ-64619178) Chemical Structure

CAS No. 2086772-26-9

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Onametostat (JNJ-64619178) Related Products

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
Sf9 Function assay Inhibition of full-length human N-terminal FLAG-tagged PRMT5/full length N-terminal His6-tagged MEP50 (unknown origin) expressed in baculovirus infected Sf9 insect cells assessed as reduction of S-adenosyl-L-homocysteine formation using human recombinant , IC50=0.00013μM 30956011
Sf9 Function assay 120 mins Inhibition of full-length human N-terminal FLAG-tagged PRMT5 expressed in Sf9 insect cells using histone H2A as peptide after 120 mins in presence of SAM by high throughput mass spectrometer assay, IC50=0.00014μM 30366617
A549 Function assay 48 hrs Inhibition of PRMT5 in human A549 cells assessed as reduction in sDMA production after 48 hrs by Hoechst Stain/HCS CellMask Deep Red Stain based immunohistochemistry method, IC50=0.00025μM 30956011
HEK293 Function assay 60 mins Inhibition of human N-terminal FLAG-tagged PRMT5 (2 to end) expressed in HEK293 cells using biotinylated H2A as substrate measured after 60 mins in presence of SAM by high throughput mass spectrometer assay, IC50=0.0063μM 29870258
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Biological Activity

Description Onametostat (JNJ-64619178) is a PRMT5 inhibitor with high selectivity and potency (subnanomolar range, PRMT5-MEP-50 IC50=0.14 nM) under different in vitro and cellular conditions, paired with favorable pharmacokinetics and safety properties.
Targets
PRMT5 [1]
0.14 nM
In vitro
In vitro

JNJ-64619178 binds into the SAM binding pocket and reaches the substrate binding pocket to inhibit PRMT5/MEP50 function in a time-dependent manner. Broad cell line panel profiling of JNJ-64619178 reveals a wide range of sensitivity, which is indicative of a genomic dependency instead of a general cytotoxic on-target consequence of PRMT5 inhibition[1].

In Vivo
In vivo

JNJ-64619178, dosed orally (10 mg/kg, every day), shows selective and efficient blockage of the methylation of SMD1/3 proteins, which are crucial components of the spliceosome and substrates of PRMT5/MEP50. JNJ-64619178 also demonstrates tumor regression in a biomarker-driven human small cell lung cancer xenograft model (NCI-H1048) and prolongs tumor growth inhibition after dosing cessation. In rodent and nonrodent toxicology studies, a tolerated dose of JNJ-64619178 has been identified, with the observed toxicity consistent with on-target activity. In summary, JNJ-64619178 has a favorable preclinical package that supports clinical testing in patients diagnosed with lung cancer and hematologic malignancies1[1].

Animal Research Animal Models C57BL/6 mice
Dosages 10 mg/kg
Administration p.o.
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT03573310 Active not recruiting
Neoplasms|Solid Tumor Adult|Non-Hodgkin Lymphoma|Myelodysplastic Syndromes
Janssen Research & Development LLC
July 13 2018 Phase 1

Chemical Information & Solubility

Molecular Weight 483.36 Formula

C22H23BrN6O2

CAS No. 2086772-26-9 SDF Download Onametostat (JNJ-64619178) SDF
Smiles C1C(C(C(C1N2C=CC3=C(N=CN=C32)N)O)O)CCC4=CC5=NC(=C(C=C5C=C4)Br)N
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 97 mg/mL ( (200.67 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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In vivo
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