1616391-65-1 Usage
Description
EPZ015666, also known as GSK3235025, is an orally available inhibitor of protein arginine methyltransferase-5 (PRMT5). It is a selective and potent inhibitor with an IC50 of 22 nM. PRMT5 is involved in various cellular processes, including tumorigenesis, and its overexpression is observed in cell lines and primary patient samples derived from lymphomas, particularly mantle cell lymphoma (MCL). EPZ015666 acts by blocking the association of PRMT5 with methylosome protein 50, which is necessary for the formation of an active methyltransferase complex.
Uses
Used in Cancer Therapy:
EPZ015666 is used as an inhibitor of PRMT5 for the treatment of various types of cancer, including lymphomas, particularly mantle cell lymphoma (MCL). It has shown dose-dependent antitumor activity in multiple in vitro and in vivo MCL models, leading to the inhibition of SmD3 methylation and cell death. It has also demonstrated potent suppression of in vivo glioblastoma tumors and significantly inhibited the growth of multiple myeloma cell lines.
Used in Anticancer Drug Development:
EPZ015666 is used as a potential drug candidate for future cancer therapy due to its potent, orally bioavailable inhibitory effect on PRMT5. It displays more than 20,000-fold selectivity for PRMT5 over other PMTs, making it a promising candidate for the development of targeted cancer treatments.
Used in Preclinical Research:
EPZ015666 is used as a research tool for studying the role of PRMT5 in cancer and other diseases. It helps researchers understand the molecular mechanisms underlying PRMT5-mediated processes and identify potential therapeutic targets for the development of novel treatments.
References
Chan-Penebre, E, et al. "A selective inhibitor of PRMT5 with in vivo and in vitro potency in MCL models." Nature Chemical Biology 11.6(2015):432.
Duncan, K. W., et al. "Structure and Property Guided Design in the Identification of PRMT5 Tool Compound EPZ015666." Acs Medicinal Chemistry Letters 7.2(2016):162-166.
http://www.sigmaaldrich.com/catalog/product/sigma/sml1421?lang=en®ion=US
References
1) Chan-Penebre?et al.?(2015),?A selective inhibitor of PRMT5 with in vivo and in vitro potency in MCL models; Nat. Chem. Biol.?11?432
2) Duncan?et al.?(2015),?Structure and Property Guided Design in the Identification of PRMT5 Toll Compound EPZ015666; ACS Med. Chem. Lett.?7?162
3) Braun?et al.?(2017),?Coordinated Splicing of Regulatory Detained Introns within Oncogenic Transcripts Creates an Exploitable Vulnerability in Malignant Glioma; Cancer Cell?32?411
4) Gulia?et al.?(2018),?Protein arginine methyltransferase 5 has prognostic relevance and is a druggable target in multiple myeloma; Leukemia?32?996
Biochem/physiol Actions
EPZ015666 (GSK3235025) is a protein arginine methyltransferase PRMT5 inhibitor with an IC50 value of of 22 nM in biochemical assays and no inhibition up to the maximum tested concentration of 50 μM against a panel of 20 other protein methyltransferases. Inhibition was uncompetitive with respect to SAM. EPZ015666 showed dose-dependent antitumor activity in multiple in vitro and in vivo mantle cell lymphoma (MCL) models with treatment of MCL cell lines leading to inhibition of SmD3 methylation and cell death.
Check Digit Verification of cas no
The CAS Registry Mumber 1616391-65-1 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,6,1,6,3,9 and 1 respectively; the second part has 2 digits, 6 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 1616391-65:
(9*1)+(8*6)+(7*1)+(6*6)+(5*3)+(4*9)+(3*1)+(2*6)+(1*5)=171
171 % 10 = 1
So 1616391-65-1 is a valid CAS Registry Number.