| Bioactivity | KN-62 is a selective and reversible inhibitor of calmodulin-dependent protein kinase II (CaMK-II) with a Ki of 0.9 μM for rat brain CaMK-II. KN-62 directly binds to the calmodulin binding site of CaMK-II. KN-62 displays noncompetitive antagonism at P2X7 receptors in HEK293 cells, with an IC50 value of approximately 15 nM. | ||||||||||||
| Invitro | KN-62 potently antagonizes ATP-stimulated Ba2+ influx into fura-2 loaded human lymphocytes with an IC50 of 12.7 nM and complete inhibition of the flux at a concentration of 500 nM[1]. KN-62 does not inhibit the activity of autophosphorylated Ca2+/CaM kinase II. KN-62 inhibits the Ca2+/calmodulin-dependent autophosphorylation of both alpha (50 kDa) and beta (60 kDa) subunits of Ca2+/CaM kinase II dose dependently in the presence or absence of exogenous substrate[2]. In human leukemic B lymphocytes, KN-62 reduces the rate of permeability increase to larger permeant cations, like ethidium, induced by Bz-ATP with an IC50 of 13.1 nM[4]. | ||||||||||||
| In Vivo | KN62 (5 mg/kg/day; ip; three times a week for 6 weeks) significantly reduces the liver metastatic tumor burden in five weeks old BALB/c athymic nude mice inoculated with TAMR-MCF-7 cells[3]. KN-62 (1 μg/site, i.c.v.) prevents the antidepressant-like behavior and antidepressant-like behaviors of ZnCl2 (10 mg/kg, p.o.)[5]. | ||||||||||||
| Name | KN-62 | ||||||||||||
| CAS | 127191-97-3 | ||||||||||||
| Formula | C38H35N5O6S2 | ||||||||||||
| Molar Mass | 721.84 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
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| Reference | [1]. Gargett CE, et al. The isoquinoline derivative KN-62 a potent antagonist of the P2Z-receptor of human lymphocytes. Br J Pharmacol. 1997 Apr;120(8):1483-90. [2]. H Hidaka, et al. Pharmacology of protein kinase inhibitors. Annu Rev Pharmacol Toxicol. 1992;32:377-97. [3]. Miso Park, et al. Involvement of the P2X7 receptor in the migration and metastasis of tamoxifen-resistant breast cancer: effects on small extracellular vesicles production. Sci Rep. 2019 Aug 12;9(1):11587. [4]. Ravi RG, et al. Potent P2X7 Receptor Antagonists: Tyrosyl Derivatives Synthesized Using a Sequential Parallel Synthetic Approach. Drug Dev Res. 2001 Oct;54(2):75-87. [5]. Manosso LM, et al. Antidepressant-like effect of zinc is dependent on signaling pathways implicated in BDNF modulation. Prog Neuropsychopharmacol Biol Psychiatry. 2015 Jun 3;59:59-67. |