EZM 2302

SKU: orb1226022

Description

EZM 2302 (EZM2302, GSK 3359088) is a potent, selective, orally available arginine methyltransferase CARM1 inhibitor with IC50 of 6 nM, with broad selectivity against other HMTases; demonstrates in vitro anti-proliferative activity consistent with specific methyl mark inhibition with IC50 of <100 nM in 9/15 multiple myeloma cell lines, decreases methylation of PABP1 (IC50 =38 nM) and SmB (IC50=18 nM); displays dose-dependent inhibition of CARM1 substrate methylation in vivo, and induces growth inhibition of human multiple myeloma tumor xenografts in mice.

Key Properties

• CAS Number: 1628830-21-6
• MW: 585.102
• Purity: >98% (HPLC)
• Formula: C₂₉H₃₇ClN₆O₅
• SMILES: O=C(N(CC1)CCC21CN(C3=NC(C4=CC(OC[C@H](O)CNC)=CC=C4Cl)=NC(C5=C(C)ON=C5C)=C3C)C2)OC
• Target: HMTase
• Solubility: 100 mM in DMSO

Bioactivity

• In Vivo:
  EZM 2302 is stable in human hepatocytes (CL<3 mL/min/kg), and moderately binds to human, mouse and rat plasma proteins with a mean fraction unbound of 0.66, 0.46 and 0.74, respectively. In mouse and rat, the plasma clearance (CL) is 43 and 91 mL/min/kg, respectively. EZM 2302 shows dose-dependent exposure and tumor growth inhibition (TGI) after 21 days in the RPMI-8226 xenograft model. Tumors in all EZM 2302 dose groups measured on day 21 show significant decreases in tumor growth compared to vehicle.
• In Vitro:
  EZM 2302 binds to CARM1 and is a selective inhibitor of CARM1 activity (IC50 = 6 nM) with broad selectivity against other histone methyltransferases. Treatment of MM cell lines with EZM 2302 leads to inhibition of PABP1 and SMB methylation and cell stasis with IC50 values in the nanomolar range (9, 31 nM, respectively). EZM 2302 inhibits the in vitro proliferation of multiple hematopoietic cell lines, with day 14 IC50 values of less than 100 nM in 9 of 15 cell lines.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

GSK 3359088 | GSK3359088 | EZM2302

Quick Database Links

Gene Symbol

HMTase