SEL-201

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

SEL-201 (SLV-2436、SEL201-88) 是一种新型强效、选择性、ATP 竞争性口服 MNK1/2 抑制剂。

SEL-201 (SLV-2436, SEL201-88) is a novel potent, selective, ATP-competitive and oral MNK1/2 inhibitor with IC5010.8/5.4 nM, respectively; displays acceptable kinome selectivity in the broad KINOMEscan (450 distinct kinases); potently suppresses MNK1/2 activity in a panel of KIT-mutant melanoma cell lines, reduces clonogenicity, migration, and lung metastasis of KIT-mutant melanoma cells both in vitro and in vivo.

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.

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.

SLV-2436 | SEL201-88

MAPK/ERK Signaling

MNK

MNK1|MNK2

Cancer

——

2095704-43-9

350.806

C19H15ClN4O

>98% (HPLC)

< 1 mg/ml refers to the product slightly soluble or insoluble

C1=CC(=CC(=C1)Cl)CN2C=C(C=CC2=O)C3=CC4=C(C=C3)C(=NN4)N

5-(3-amino-1H-indazol-6-yl)-1-[(3-chlorophenyl)methyl]-1,2-dihydropyridin-2-one

(-20℃)

With Ice Pack

≥ 2 years