Synonym
LY83583; LY-83583; LY 83583. LY83583; LY-83583; LY 83583.
IUPAC/Chemical Name
6-(phenylamino)quinoline-5,8-dione
InChi Key
GXIJYWUWLNHKNW-UHFFFAOYSA-N
InChi Code
InChI=1S/C15H10N2O2/c18-13-9-12(17-10-5-2-1-3-6-10)15(19)11-7-4-8-16-14(11)13/h1-9,17H
SMILES Code
O=C(C(NC1=CC=CC=C1)=C2)C3=C(N=CC=C3)C2=O
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
LY83583 is a cell-permeable and competitive inhibitor of soluble guanylate cyclase (sGC) with an IC50 value of 2 µM.
In vitro activity:
In vitro screening using a recombinant catalytic domain of CaMps1p identified LY83583 (6-anilino-5,8-quinolinedione), known as a guanylate cyclase inhibitor, to be blocking CaMps1p kinase activity. In addition to its in vitro kinase inhibition, LY83583 reduced the growth rate of C. albicans. LY83583 showed specific inhibition for CaMps1p with no effect on hMps1p activity.
Reference: Biochem Biophys Res Commun. 2011 Jun 10;409(3):418-23. https://pubmed.ncbi.nlm.nih.gov/21586273/
In vivo activity:
These relationships were studied by monitoring the effects of muscarinic agonists on tension and cyclic GMP levels in rabbit left atrial strips and aortic rings, in the presence and absence of the cyclic GMP lowering agent, LY83583. LY83583 completely blocked both the cyclic GMP increase and the relaxation caused by acetylcholine in rabbit aortic rings with intact endothelial cells.
Reference: Can J Physiol Pharmacol. 1987 Sep;65(9):1913-7. https://pubmed.ncbi.nlm.nih.gov/2825946/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
200.0 |
799.18 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
250.26
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Tsuda K, Nishiya N, Umeyama T, Uehara Y. Identification of LY83583 as a specific inhibitor of Candida albicans MPS1 protein kinase. Biochem Biophys Res Commun. 2011 Jun 10;409(3):418-23. doi: 10.1016/j.bbrc.2011.05.010. Epub 2011 May 8. PMID: 21586273.
2. Lodygin D, Menssen A, Hermeking H. Induction of the Cdk inhibitor p21 by LY83583 inhibits tumor cell proliferation in a p53-independent manner. J Clin Invest. 2002 Dec;110(11):1717-27. doi: 10.1172/JCI16588. PMID: 12464677; PMCID: PMC151636.
3. Diamond J. Effects of LY83583, nordihydroguaiaretic acid, and quinacrine on cyclic GMP elevation and inhibition of tension by muscarinic agonists in rabbit aorta and left atrium. Can J Physiol Pharmacol. 1987 Sep;65(9):1913-7. doi: 10.1139/y87-297. PMID: 2825946.
4. MacLeod KM, Diamond J. Effects of the cyclic GMP lowering agent LY83583 on the interaction of carbachol with forskolin in rabbit isolated cardiac preparations. J Pharmacol Exp Ther. 1986 Jul;238(1):313-8. PMID: 3014120.
In vitro protocol:
1. Tsuda K, Nishiya N, Umeyama T, Uehara Y. Identification of LY83583 as a specific inhibitor of Candida albicans MPS1 protein kinase. Biochem Biophys Res Commun. 2011 Jun 10;409(3):418-23. doi: 10.1016/j.bbrc.2011.05.010. Epub 2011 May 8. PMID: 21586273.
2. Lodygin D, Menssen A, Hermeking H. Induction of the Cdk inhibitor p21 by LY83583 inhibits tumor cell proliferation in a p53-independent manner. J Clin Invest. 2002 Dec;110(11):1717-27. doi: 10.1172/JCI16588. PMID: 12464677; PMCID: PMC151636.
In vivo protocol:
1. Diamond J. Effects of LY83583, nordihydroguaiaretic acid, and quinacrine on cyclic GMP elevation and inhibition of tension by muscarinic agonists in rabbit aorta and left atrium. Can J Physiol Pharmacol. 1987 Sep;65(9):1913-7. doi: 10.1139/y87-297. PMID: 2825946.
2. MacLeod KM, Diamond J. Effects of the cyclic GMP lowering agent LY83583 on the interaction of carbachol with forskolin in rabbit isolated cardiac preparations. J Pharmacol Exp Ther. 1986 Jul;238(1):313-8. PMID: 3014120.
1: Tsuda K, Nishiya N, Umeyama T, Uehara Y. Identification of LY83583 as a specific inhibitor of Candida albicans MPS1 protein kinase. Biochem Biophys Res Commun. 2011 Jun 10;409(3):418-23. doi: 10.1016/j.bbrc.2011.05.010. Epub 2011 May 8. PubMed PMID: 21586273.
2: Lodygin D, Menssen A, Hermeking H. Induction of the Cdk inhibitor p21 by LY83583 inhibits tumor cell proliferation in a p53-independent manner. J Clin Invest. 2002 Dec;110(11):1717-27. PubMed PMID: 12464677; PubMed Central PMCID: PMC151636.
3: Kumagai Y, Midorikawa K, Nakai Y, Yoshikawa T, Kushida K, Homma-Takeda S, Shimojo N. Inhibition of nitric oxide formation and superoxide generation during reduction of LY83583 by neuronal nitric oxide synthase. Eur J Pharmacol. 1998 Nov 6;360(2-3):213-8. PubMed PMID: 9851588.
4: Leinders-Zufall T, Zufall F. Block of cyclic nucleotide-gated channels in salamander olfactory receptor neurons by the guanylyl cyclase inhibitor LY83583. J Neurophysiol. 1995 Dec;74(6):2759-62. PubMed PMID: 8747232.
5: Luo D, Das S, Vincent SR. Effects of methylene blue and LY83583 on neuronal nitric oxide synthase and NADPH-diaphorase. Eur J Pharmacol. 1995 Aug 15;290(3):247-51. PubMed PMID: 7589219.
6: Lee YS, Wurster RD. Mechanism of potentiation of LY83583-induced growth inhibition by sodium nitroprusside in human brain tumor cells. Cancer Chemother Pharmacol. 1995;36(4):341-4. PubMed PMID: 7628054.
7: Feng CJ, Cheng DY, Kaye AD, Kadowitz PJ, Nossaman BD. Influence of N omega-nitro-L-arginine methyl ester, LY83583, glybenclamide and L158809 on pulmonary circulation. Eur J Pharmacol. 1994 Sep 22;263(1-2):133-40. PubMed PMID: 7821344.
8: Lüönd RM, McKie JH, Douglas KT. A direct link between LY83583, a selective repressor of cyclic GMP formation, and glutathione metabolism. Biochem Pharmacol. 1993 Jun 22;45(12):2547-9. PubMed PMID: 8101080.
9: Sundqvist T, Axelsson KL. The cGMP modulator, LY83583 alters oxygen metabolites differently in cultured endothelial cells and isolated neutrophilic granulocytes. Pharmacol Toxicol. 1993 Mar;72(3):169-74. PubMed PMID: 8390653.
10: Kontos HA, Wei EP. Hydroxyl radical-dependent inactivation of guanylate cyclase in cerebral arterioles by methylene blue and by LY83583. Stroke. 1993 Mar;24(3):427-34. PubMed PMID: 8095358.
11: Axelsson KL, Ahlner J, Torfgård K. Effect of pertussis toxin and the cGMP lowering agent LY83583 on the relaxation induced by nitrates in isolated bovine mesenteric artery. A comparison between glyceryl trinitrate, isosorbide dinitrate and isosorbide 5-mononitrate. Z Kardiol. 1989;78 Suppl 2:11-3; discussion 64-7. PubMed PMID: 2555977.
12: Malta E, Macdonald PS, Dusting GJ. Inhibition of vascular smooth muscle relaxation by LY83583. Naunyn Schmiedebergs Arch Pharmacol. 1988 Apr;337(4):459-64. PubMed PMID: 2900475.
13: Diamond J. Effects of LY83583, nordihydroguaiaretic acid, and quinacrine on cyclic GMP elevation and inhibition of tension by muscarinic agonists in rabbit aorta and left atrium. Can J Physiol Pharmacol. 1987 Sep;65(9):1913-7. PubMed PMID: 2825946.
14: MacLeod KM, Diamond J. Effects of the cyclic GMP lowering agent LY83583 on the interaction of carbachol with forskolin in rabbit isolated cardiac preparations. J Pharmacol Exp Ther. 1986 Jul;238(1):313-8. PubMed PMID: 3014120.
15: Diamond J, Chu EB. A novel cyclic GMP-lowering agent, LY83583, blocks carbachol-induced cyclic GMP elevation in rabbit atrial strips without blocking the negative inotropic effects of carbachol. Can J Physiol Pharmacol. 1985 Aug;63(8):908-11. PubMed PMID: 3000562.
16: Schmidt MJ, Sawyer BD, Truex LL, Marshall WS, Fleisch JH. LY83583: an agent that lowers intracellular levels of cyclic guanosine 3',5'-monophosphate. J Pharmacol Exp Ther. 1985 Mar;232(3):764-9. PubMed PMID: 2857787.
