A PRMT5 inhibitor
JNJ-64619178 is a PRMT5 inhibitor with high selectivity and potency (PRMT5-MEP-50, IC50=0.14 nM), good pharmacokinetic properties and safety.
JNJ-64619178 can be combined with a SAM binding pocket to inhibit the function of PRMT/MEP50 in a time-dependent manner. Various cell lines exhibited different degrees of sensitivity to JNJ-64619178, indicating that JNJ-64619178 inhibits PRMT5 mainly by genomic rather than general targeted cytotoxicity [1].
The methylation of SMD1/3 protein can be selectively and effectively prevented by oral administration of 10 mg/kg JNJ-64619178 per day. SMD1/3 is a key component of the splice and a substrate for PRMT5/MEP50. In the biomarker-driven human small cell lung cancer xenograft model (NCI-H1048), JNJ-64619178 can cause tumor regression and prolong tumor growth inhibition after termination of administration [1].
Reference:
[1] Dirk Brehmer, et al. 108th Annu Meet Am Assoc Cancer Research
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