955011-81-1

Basic information

• Product Name: KYS₀₅₀₈₉
• Synonyms: KYS₀₅₀₈₉
• CAS NO: 955011-81-1
• Molecular Weight: 498.668
• Mol File: 955011-81-1.mol
• Article Data: 6

Chemical Properties

• CAS DataBase Reference: KYS₀₅₀₈₉(CAS DataBase Reference)
• NIST Chemistry Reference: KYS₀₅₀₈₉(955011-81-1)
• EPA Substance Registry System: KYS₀₅₀₈₉(955011-81-1)

Safety Data

• Hazardous Substances Data: 955011-81-1(Hazardous Substances Data)

Upstream product

• 839672-50-3 methyl 3-[2-((4-biphenyl)iminomethyleneamino)phenyl]acrylate 
• 39228-29-0 (E)-methyl 2-nitrocinnamate 
• 88939-75-7 methyl (2E)-3-(2-aminophenyl)propenoate 
• 1400645-09-1 methyl trans-2-(3-biphenylureido)cinnamate 
• 612-41-9 2-nitrocinnamic acid 
• 138386-58-0 (E)-methyl 3-[2-(triphenylphosphoranylidenamino)phenyl]-propenoate 
• 51644-96-3 5-tert-butoxycarbonylamino-1-aminopentane 
• 39228-29-0 methyl 2-nitrocinnamate 
• 92-92-2 biphenyl-4-carboxylic acid 
• 88939-75-7 methyl β-(o-aminophenyl)acrylate 
• 34237-69-9 N,N'-di-(tert-butoxycarbonyl)-1,5-diaminopentane 
• 56992-95-1 N,N'-dimethylpentane-1,5-diamine 
• 462-94-2 1,5-diaminopentane 
• 124073-01-4 C₁₂H₂₆N₂O₂ 

Relevant articles and documents

Discovery of potent T-type calcium channel blocker

The intensive SAR study of 3,4-dihydroquinazoline series led to the most potent compound 10 (KYS05090: IC50 = 41 ± 1 nM) against T-type calcium channel and its potency is nearly comparable to that of Kurtoxin. As a small organic molecule, this compound showed the highest blocking activity reported to date.

In vitro cytotoxicity on human ovarian cancer cells by T-type calcium channel blockers

The growth inhibition of human cancer cells via T-type Ca2+ channel blockade has been well known. Herein, a series of new 3,4-dihydroquinazoline derivatives were synthesized via a brief SAR study on KYS05090 template and evaluated for both T-type Ca2+ channel (Ca v3.1) blockade and cytotoxicity on three human ovarian cancer cells (SK-OV-3, A2780 and A2780-T). Most of compounds except 6i generally exhibited more potent cytotoxicity on SK-OV-3 than mibefradil as a positive control regardless of the degree of T-type channel blockade. In particular, eight compounds (KYS05090, 6a and 6c-6h) showing strong channel blockade exhibited almost equal and more potent cytotoxicity on A2780 when compared to mibefradil. On A2780-T paclitaxel-resistant human ovarian carcinoma, two compounds (KYS05090 and 6d) were 20-fold more active than mibefradil. With respect to cell cycle arrest effect on A2780 and A2780-T cells, KYS05090 induced large proportion of sub-G1 phase in the cell cycle progression of A2780 and A2780-T, meaning the induction of cancer cell death instead of cell cycle arrest via blocking T-type Ca2+ channel. Among new analogues, compounds 6g and 6h induced cell cycle arrest at G1 phase of A2780 and A2780-T cells in dose-dependent manner and exhibited strong anti-proliferation effects of ovarian cancer cells by blocking T-type Ca2+ channel. Furthermore, 6g and 6h possessing strong cytotoxic effects could induce apoptosis of A2780 cells, which was detected by confocal micrographs using DAPI staining.

T-type Ca2+ channel blockers suppress the growth of human cancer cells

In order to further clarify the role of T-type Ca2+ channels in cell proliferation, we have measured the growth inhibition of human cancer cells by using our potent T-type Ca2+ channel blockers. As a result, KYS05090, a most potent T-type Ca2+ channel blocker, was found to be as potent as doxorubicin against some human cancer cells without acute toxicity. Therefore, this letter provides the biological results that T-type calcium channel is important in regulating the important cellular phenotype transition leading to cell proliferation, and thus novel T-type Ca2+ channel blocker presents new prospects for cancer treatment.