MARK-IN-2

• CAT Number: I019967
• CAS Number: 1314893-26-9
• Molecular Formula: C18H18ClF2N5OS
• Molecular Weight: 425.88
• Purity: ≥95%
• Synonyms: N-[(1R,6R)-6-amino-2,2-difluorocyclohexyl]-4-(6-chloropyrazolo[1,5-a]pyrimidin-3-yl)-5-methylthiophene-2-carboxamide
• InChI: InChI=1S/C18H18ClF2N5OS/c1-9-11(12-7-24-26-8-10(19)6-23-16(12)26)5-14(28-9)17(27)25-15-13(22)3-2-4-18(15,20)21/h5-8,13,15H,2-4,22H2,1H3,(H,25,27)/t13-,15-/m1/s1
• InChIKey: NGFGTMFVWSDFPS-UKRRQHHQSA-N
• SMILES: CC1=C(C=C(S1)C(=O)NC2C(CCCC2(F)F)N)C3=C4N=CC(=CN4N=C3)Cl

MARK-IN-2 is a potent microtubule affinity regulating kinase (MARK) inhibitor with an IC50 of 5 nM.
MARK-IN-2 (Compound 27) is a potent MARK inhibitor. Inhibition of MARK represents a potentially attractive means of arresting neurofibrillary tangle pathology in Alzheimer’s disease. MARK-IN-2 inhibits MARK3 with an IC50 of 5 nM. MARK-IN-2 also inhibits MARK3 in primary cell culture of rat cortical neurons with an IC50 of 280 nM[1].
Characterization of the i.v. pharmacokinetic properties of MARK-IN-2 in rat and dog reveals reasonable volumes of distribution but moderate to high clearance and short half-lives. MARK-IN-2 (Compound 27) has moderate terminal elimination half-life (t1/2=0.7 h, and 1 h for rat and dog) [1].

Reference

[1]. Sloman DL, et al. Optimization of microtubule affinity regulating kinase (MARK) inhibitors with improved physical properties. Bioorg Med Chem Lett. 2016 Sep 1;26(17):4362-6.
 [Content Brief]