Ruboxistaurin mesylate

Names

[ CAS No. ]:
192050-59-2

[ Name ]:
Ruboxistaurin mesylate

[Synonym ]:
9-((Dimethylamino)methyl)-6,7,10,11-tetrahydro-9H,18H-5,21:12,17-dimethenodibenzo(E,k)pyrrolo(3,4-h)(1,4,13)oxadiazacyclohexadecine-18,20(19H)-dione,methanesulfonate,(9S)
13-((DIMETHYLAMINO)METHYL)-10,11,14,15-TETRAHYDRO-4,9:16,21-DIMETHENO-1H,13H-DIBENZO(E,K)PYRROLO(3,4-H)(1,4,13) OXADIAZACYCLOHEXADECENE-1,3(2H)-DIONE METHANESULFONATE
Ruboxistaurin mesylate
(S)-9-((dimethylamino)methyl)-6,7,10,11-tetrahydro-9H,18H-5,21:12,17-dimethenodibenzo(e,k)pyrrolo(3,4h)(1,4,13)oxadiazacyclohexadecine-18,20(19H)-dione mesylate
UNII-6V860VW8AO

Biological Activity

[Description]:

Ruboxistaurin (LY333531) mesylate is an orally active, selective and ATP competitive PKCβ inhibitor with IC50 values of 4.7 and 5.9 nM for PKCβI and PKCβII, respectively. Ruboxistaurin mesylate can be used for the research of eye disorders, heart failure and diabetes[1][2][3][4].

[Related Catalog]:

Signaling Pathways >> Epigenetics >> PKC
Research Areas >> Cardiovascular Disease
Research Areas >> Metabolic Disease
Signaling Pathways >> TGF-beta/Smad >> PKC

[Target]

PKC-βI:4.7 nM (IC50)

PKC-βII:5.9 nM (IC50)

PKCη:52 nM (IC50)

PKCδ:250 nM (IC50)

PKCγ:300 nM (IC50)

PKCα:360 nM (IC50)

PKCε:600 nM (IC50)


[In Vitro]

Ruboxistaurin mesylate 对 PKCα，PKCβI，PKCβII，PKCγ，PKCδ，PKCε 和 PKCη 的 IC50 值分别为 0.36，0.0047，0.0059，0.30，0.25，0.60 和 0.052 μM[1]。 Ruboxistaurin mesylate 抑制 Ca calmodulin 和大鼠脑 PKC 的 IC50 分别为 6.2 和 0.32 μM[1]。 Ruboxistaurin mesylate (10 和 400 nM；4 天) 显著抑制正常血糖 (NG) 条件下葡萄糖诱导的单核细胞粘附[3]。

[In Vivo]

Ruboxistaurin mesylate (0.1, 1.0 和 10.0 mg/kg；口服，每日 1 次，共 3 周) 抑制糖尿病早期视网膜微循环中白细胞滞留的增加[4]。 Animal Model: Male long-evans rats with streptozotocin induced diabetes[4] Dosage: 0.1, 1.0 and 10.0 mg/kg Administration: Oral administration; 0.1, 1.0 and 10.0 mg/kg, once daily for 4 weeks Result: Significantly decreased the number of leukocytes in the retinal microcirculation of rats with streptozotocin induced diabetes.

[References]

[1]. Jirousek MR, et al. (S)-13-[(dimethylamino)methyl]-10,11,14,15-tetrahydro-4,9:16, 21-dimetheno-1H, 13H-dibenzo[e,k]pyrrolo[3,4-h][1,4,13]oxadiazacyclohexadecene-1,3(2H)-d ione (LY333531) and related analogues: isozyme selective inhibitors of protein kinase C beta. J Med Chem. 1996;39(14):2664-2671.  

[2]. Ruboxistaurin: LY 333531. Drugs R D. 2007;8(3):193-199.  

[3]. Kunt T, et al. The beta-specific protein kinase C inhibitor ruboxistaurin (LY333531) suppresses glucose-induced adhesion of human monocytes to endothelial cells in vitro. J Diabetes Sci Technol. 2007 Nov;1(6):929-35.  

[4]. Nonaka A, et al. PKC-beta inhibitor (LY333531) attenuates leukocyte entrapment in retinal microcirculation of diabetic rats. Invest Ophthalmol Vis Sci. 2000 Aug;41(9):2702-6.  

Chemical & Physical Properties

[ Molecular Formula ]:
C29H32N4O6S

[ Molecular Weight ]:
564.65300

[ Exact Mass ]:
564.20400

[ PSA ]:
134.74000

[ LogP ]:
4.37440

Related Compounds