K00546 

K00546 is a potent CDK1 and CDK2 inhibitor with IC₅₀s of 0.6 nM and 0.5 nM for CDK1/cyclin B and CDK2/cyclin A, respectively. K00546 is also a potent CDC2-like kinase 1 (CLK1) and CLK3 inhibitor with IC₅₀s of 8.9 nM and 29.2 nM, respectively^[1][2][3].

K00546 binds to the SLK ATP-binding site forming three hydrogen bonds with the kinase hinge residues E109 and C111. The sulphamoyl moiety of K00546 also interacts with the main chain of L40^[1].
K00546 (compound 3n) also inhibits PKA, casein kinase-1, MAP kinase (ERK-2), calmodulin kinase, VEGF-R2, GSK-3 and PDGF-Rβ with IC₅₀ values of 5.2 μM, 2.8 μM, 1.0 μM, 8.9 μM, 0.032 μM, 0.14 μM and 1.6 μM, respectively^[2].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

425.44

Solid

C₁₅H₁₃F₂N₇O₂S₂

443798-47-8

S=C(N1N=C(NC2=CC=C(S(=O)(N)=O)C=C2)N=C1N)NC3=C(F)C=CC=C3F

Room temperature in continental US; may vary elsewhere.

• [1]. Ashley C W Pike, et al. Activation segment dimerization: a mechanism for kinase autophosphorylation of non-consensus sites. EMBO J. 2008 Feb 20;27(4):704-14.  [Content Brief]

  [2]. Ronghui Lin, et al. 1-Acyl-1H-[1,2,4]triazole-3,5-diamine analogues as novel and potent anticancer cyclin-dependent kinase inhibitors: synthesis and evaluation of biological activities. J Med Chem. 2005 Jun 30;48(13):4208-11.  [Content Brief]

  [3]. Oleg Fedorov, et al. Specific CLK inhibitors from a novel chemotype for regulation of alternative splicing. Chem Biol. 2011 Jan 28;18(1):67-76.  [Content Brief]