生物活性

• 描述PRMT5 is a protein arginine methyltransferase that catalyzes H4R3me2 and H3R8me2. It is active on non-histone substrates, such as p53 and programmed cell death 4, and acts as a transcriptional repressor. GSK3326595 is a potent, selective inhibitor of PRMT5 with an IC50 value of 6.2 ± 0.8 nM^[1]. It inhibited tumor growth both in vitro and in animal models^[2]. Treatment with GSK3326595 (40 mg/kg from day 10) plus anti-PD1 antibodies (200 μg/mouse at days, 8, 11, 14, 17 and 20) augmented the anti-tumor response, reflected in reduced tumor size in both B16 (Fig. 8E; fig. S10C and S10D) and YUMM1.7 melanoma models^[3].
• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT02783300	Cancer Neopla... more >>sms Collapse <<	Phase 1	Recruiting	June 15, 2020	United States, Florida ... more >> GSK Investigational Site Recruiting Miami, Florida, United States, 33136 Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com    Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com    GSK Investigational Site Recruiting Miami, Florida, United States, 33136 Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com    Contact: EU GSK Clinical Trials Call Centre    877-379-3718    GSKClinicalSupportHD@gsk.com    Principal Investigator: Izidore S Lossos          United States, New York GSK Investigational Site Recruiting New York, New York, United States, 10065 Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com    Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com    GSK Investigational Site Recruiting New York, New York, United States, 10065 Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com    Contact: EU GSK Clinical Trials Call Centre    877-379-3718    GSKClinicalSupportHD@gsk.com    Principal Investigator: Mrinal M. Gounder          United States, Texas GSK Investigational Site Not yet recruiting Dallas, Texas, United States, 75230 Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com    Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com    GSK Investigational Site Recruiting Dallas, Texas, United States, 75230 Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com    Contact: EU GSK Clinical Trials Call Centre    877-379-3718    GSKClinicalSupportHD@gsk.com    Principal Investigator: James Strauss          GSK Investigational Site Recruiting San Antonio, Texas, United States, 78229 Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com    Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com    GSK Investigational Site Recruiting San Antonio, Texas, United States, 78229 Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com    Contact: EU GSK Clinical Trials Call Centre    877-379-3718    GSKClinicalSupportHD@gsk.com    Principal Investigator: Drew W Rasco          Canada, Ontario GSK Investigational Site Recruiting Toronto, Ontario, Canada, M5G 1X6 Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com    Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com    GSK Investigational Site Recruiting Toronto, Ontario, Canada, M5G 1X Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com    Contact: EU GSK Clinical Trials Call Centre    877-379-3718    GSKClinicalSupportHD@gsk.com    Principal Investigator: Lillian Siu          France GSK Investigational Site Recruiting Bordeaux Cedex, France, 33076 Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com    Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com    GSK Investigational Site Recruiting Bordeaux Cedex, France, 33076 Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com    Contact: EU GSK Clinical Trials Call Centre    877-379-3718    GSKClinicalSupportHD@gsk.com    Principal Investigator: Antoine Italiano          GSK Investigational Site Recruiting Lyon Cedex 08, France, 69373 Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com    Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com    GSK Investigational Site Recruiting Lyon Cedex 08, France, 69373 Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com    Contact: EU GSK Clinical Trials Call Centre    877-379-3718    GSKClinicalSupportHD@gsk.com    Principal Investigator: Philippe Cassier          GSK Investigational Site Recruiting Villejuif cedex, France, 94805 Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com    Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com    GSK Investigational Site Recruiting Villejuif cedex, France, 94805 Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com    Contact: EU GSK Clinical Trials Call Centre    877-379-3718    GSKClinicalSupportHD@gsk.com    Principal Investigator: Sophie Postel-Vinay          Netherlands GSK Investigational Site Recruiting Amsterdam, Netherlands, 1066 CX Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com    Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com    GSK Investigational Site Recruiting Amsterdam, Netherlands, 1066 C Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com    Contact: EU GSK Clinical Trials Call Centre    877-379-3718    GSKClinicalSupportHD@gsk.com    Principal Investigator: Frans L. Opdam          GSK Investigational Site Not yet recruiting Leiden, Netherlands, 2333 Z Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com    Contact: EU GSK Clinical Trials Call Centre    877-379-3718    GSKClinicalSupportHD@gsk.com    GSK Investigational Site Not yet recruiting Rotterdam, Netherlands, 3075 E Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com    Contact: EU GSK Clinical Trials Call Centre    877-379-3718    GSKClinicalSupportHD@gsk.com Collapse <<
  NCT03614728	Neoplasms	Phase 2	Not yet recruiting	December 15, 2022	United States, Florida ... more >> GSK Investigational Site Not yet recruiting Miami, Florida, United States, 33136 Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com    Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com Collapse <<

• 参考文献

• [1] Vinet M, Suresh S, Maire V, Monchecourt C, Némati F, Lesage L, Pierre F, Ye M, Lescure A, Brisson A, Meseure D, Nicolas A, Rigaill G, Marangoni E, Del Nery E, Roman-Roman S, Dubois T. Protein arginine methyltransferase 5: A novel therapeutic target for triple-negative breast cancers. Cancer Med. 2019 May;8(5):2414-2428

  [2] Dose Escalation Study of GSK3326595 in Participants With Solid Tumors and Non-Hodgkin's Lymphoma (NHL)

  [3] Kim H, Kim H, Feng Y, Li Y, Tamiya H, Tocci S, Ronai ZA. PRMT5 control of cGAS/STING and NLRC5 pathways defines melanoma response to antitumor immunity. Sci Transl Med. 2020 Jul 8;12(551):eaaz5683.