| Bioactivity | WNK-IN-11 is an allosteric With-No-Lysine (WNK) kinase inhibitor, with an IC50 of 4 nM for WNK1. | ||||||||||||
| Target | IC50: 4 nM (WNK1). | ||||||||||||
| Invitro | WNK-IN-11 (compound 11) shows IC50<2 μM in the cellular OSR1 phosphorylation assay with reasonable aqueous solubility, albeit with still rather high microsomal clearance. WNK-IN-11 shows ATP noncompetitive inhibition. When tested against a panel of 440 human kinases at 10 μM concentration, 2500-fold above enzyme IC50 value, WNK-IN-11 shows excellent selectivity with only a few significant off-target kinase inhibitions, most notably BTK and feline encephalitis virus-related (FER) kinase, neither of which are implicated for blood pressure regulation. This excellent selectivity profile is consistent with the predicted allosteric binding mode outside the highly conserved ATP-pocket[1]. | ||||||||||||
| Name | WNK-IN-11 | ||||||||||||
| CAS | 2123489-30-3 | ||||||||||||
| Formula | C21H21Cl2N5OS | ||||||||||||
| Molar Mass | 462.40 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
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| Reference | [1]. Yamada K, et al. Optimization of Allosteric With-No-Lysine (WNK) Kinase Inhibitors and Efficacy in Rodent Hypertension Models. J Med Chem. 2017 Aug 24;60(16):7099-7107. |