XMD8-92

    • 货号:MC0543
      • CasNo:
      • 1234480-50-2
      • 分子式:
      • C26H30N6O3
      • 纯度:
      • >98%
      • 靶点:
      • ERK
      • IC50:
      • Kd: 80 nM (ERK5/BMK1)[1]
      • 体外研究:
      • XMD8-92 exhibits the greatest affinity towards BMK1 with a measured dissociation constant (Kd) of 80 nM, while DCAMKL2, TNK1 and PLK4 exhibit Kd’s of 190, 890 and 600 nM, respectively. XMD8-92 is profiled against all detectable kinases in HeLa cell lysates using the KiNativ method and is found to be about 10-fold more selective for BMK1 with a IC50 of 1.5 μM than the most potent off-targets, TNK1 (IC50=10 μM) and ACK1 (aka TNK2, IC50=18 μM). Other weak off-targets include the kinase domain 2 of RSK1 and RSK2, PIK4A and PIK4B, and FAK. Notably, MEK5 is not significantly inhibited by XMD8-92 at up to 50 μM[1]. XMD8-92 shows high selectivity to BMK1 in an in vitro ATP-site competition binding assay against 402 kinases as well as in the KiNativ method against all detectable kinases in HeLa cell lysates. XMD8-92 blocks EGF-induced activation of BMK1 with IC50 of 240 nM and, with concentration as high as 5 μM, XMD8-92 has no inhibitory effect on ERK1/2 activation by EGF[2].
      • 体内研究:
      • XMD8-92 significantly inhibits tumor growth in vivo by 95%. The pharmacokinetics of XMD8-92 is evaluated in Sprague-Dawley rats given a single intravenous or oral dose. XMD8-92 is found to have a 2.0 hr half life clearance of 26 mL/min/kg. XMD8-92 has moderate tissue distribution with a calculated volume of distribution of 3.4 L/kg. XMD8-92 has high oral bioavailability with 69% of the dose absorbed. After a single oral dose of 2 mg/kg, maximal plasma concentrations of approximately 500 nM are observed by 30 minutes, with 34 nM remaining 8 hr post dose. In tolerability experiments, high plasma concentrations of drug (approximately 10 μM following IP dosing of 50 mg/kg) are maintained throughout the 14 days. XMD8-92 appeares to be well tolerated and the mice appeared healthy with no sign of distress. No vasculature instability is observed in the XMD8-92-treated mice[1]. XMD8-92 treatment in both immunocompetent and immunodeficient mice blocked the growth of lung and cervical xenograft t
      • 简介:
      • XMD8-92 is highly selective ERK5/BMK1 inhibitor with Kd values of 80, 190, 600 and 890 nM for BMK1, DCAMKL2, PLK4 and TNK1 respectively ; displays selectivity over 402 diverse kinases. Kd: 80 nM (ERK5/BMK1)[1]
      • 特异性:
      • Target: ERK. Fields: XMD8-92 is highly selective ERK5/BMK1 inhibitor with Kd values of 80, 190, 600 and 890 nM for BMK1, DCAMKL2, PLK4 and TNK1 respectively ; displays selectivity over 402 diverse kin
      • 稀释:
      • Kd: 80 nM (ERK5/BMK1)[1]
      • 浓度:
      • >98%
      • 储存:
      • 2 years -20°C Powder, 2 weeks4°C in DMSO,6 months-80°C in DMSO
      • 其他名称:
      • XMD 8-92
      • 分子量:
      • 474.57
      • 产品图片