SLV-2436 是一种高效且 ATP 竞争性的 MNK1 和 MNK2 抑制剂，IC₅₀ 分别为 10.8 nM 和 5.4 nM。

SLV-2436 is a highly potent and ATP-competitive inhibitor of MNK1 and MNK2 with IC 50 s of 10.8 ?nM and 5.4 nM, respectively.

Solid

MNK2 5.4 nM (IC50) MNK1 10.8 nM (IC50

To confirm the kinome selectivity of SLV-2436 (SEL201), the broad KINOMEscan competitive binding assay is performed at 1 μM, which includes 450 distinct kinases. The observed binding profile for SLV-2436 is significantly concentrated in the CAMK family of kinases that comprises MNK1 and MNK2. SLV-2436-treated KIT -mutant melanoma cells have lower oncogenicity and reduced metastatic ability. has not independently confirmed the accuracy of these methods. They are for reference only.

To investigate the pharmacodynamic properties of SLV-2436 (SEL201), 5 consecutive oral doses of 10, 25, and 50 mg/kg are administered to mice every 12 hours (twice-daily schedule). At the 10 mg/kg twice-daily dosage, 4 hours after the fifth administration, a low plasma concentration of 125 ng/mL SLV-2436 is determined. However, dosing at 25 and 50 mg/kg twice daily, equivalent to 50 and 100 mg/kg/d of SLV-2436, yields substantially increased dose-dependent plasma exposure, reaching an average level of 1,299 ng/mL and 2,075 ng/mL, respectively. At the 24-hour time point, SLV-2436 is still detectable in the plasma, with dose-dependent concentrations of 9, 73, and 124 ng/mL in the 10, 25, and 50 mg/kg twice-daily treatment groups. Oral (p.o.) administration of SLV-2436 at the dosage of 50 mg/kg twice daily, that is, 100 mg/kg/d, for 37 days is well tolerated in mice.

Room temperature in continental US; may vary elsewhere.

Powder -20°C 3 years；4°C 2 years

[1]. Zhan Y, et al. MNK1/2 inhibition limits oncogenicity and metastasis of KIT-mutant melanoma. J Clin Invest. 2017 Nov 1;127(11):4179-4192.

In Vitro: DMSO : ≥ 100 mg/mL (285.06 mM)配制储备液