Onametostat (JNJ-64619178)

Catalog No.S8624 Batch:S862402

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Technical Data

Formula

C22H23BrN6O2
Molecular Weight 483.36 CAS No. 2086772-26-9
Solubility (25°C)* In vitro DMSO 97 mg/mL (200.67 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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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

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

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].

Protocol (from reference)

Animal Study:

[3]
  • Animal Models

    C57BL/6 mice

  • Dosages

    10 mg/kg

  • Administration

    p.o.

Selleck's Onametostat (JNJ-64619178) has been cited by 8 publications

Heterogeneity-driven phenotypic plasticity and treatment response in branched-organoid models of pancreatic ductal adenocarcinoma [ Nat Biomed Eng, 2024, 10.1038/s41551-024-01273-9] PubMed: 39658630
Inhibition of epigenetic and cell cycle-related targets in glioblastoma cell lines reveals that onametostat reduces proliferation and viability in both normoxic and hypoxic conditions [ Sci Rep, 2024, 14(1):4303] PubMed: 38383756
Development and validation of a generic methyltransferase enzymatic assay based on an SAH riboswitch [ SLAS Discov, 2024, 29(4):100161] PubMed: 38788976
Long non-coding RNA-derived peptides are immunogenic and drive a potent anti-tumour response [ Nat Commun, 2023, 14(1):1078] PubMed: 36841868
PRMT5 reduces immunotherapy efficacy in triple-negative breast cancer by methylating KEAP1 and inhibiting ferroptosis [ J Immunother Cancer, 2023, 11(6)e006890] PubMed: 37380368
Epigenetic drug screening defines a PRMT5 inhibitor-sensitive pancreatic cancer subtype [ JCI Insight, 2022, 7(10)e151353] PubMed: 35439169
Tadalafil increases the antitumor activity of 5-FU through inhibiting PRMT5-mediated glycolysis and cell proliferation in colorectal cancer [ Cancer Metab, 2022, 10(1):22] PubMed: 36474242
Acquired resistance to PRMT5 inhibition induces concomitant collateral sensitivity to paclitaxel [ Proc Natl Acad Sci U S A, 2021, 118(34)e2024055118] PubMed: 34408017

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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