Synonym
LY393558; LY 393558; LY-393558;
IUPAC/Chemical Name
1-(2-(4-(6-fluoro-1H-indol-3-yl)-3,6-dihydropyridin-1(2H)-yl)ethyl)-3-isopropyl-6-(methylsulfonyl)-3,4-dihydro-1H-benzo[c][1,2,6]thiadiazine 2,2-dioxide
InChi Key
QUSLYAPLTMMCFE-UHFFFAOYSA-N
InChi Code
InChI=1S/C26H31FN4O4S2/c1-18(2)31-17-20-14-22(36(3,32)33)5-7-26(20)30(37(31,34)35)13-12-29-10-8-19(9-11-29)24-16-28-25-15-21(27)4-6-23(24)25/h4-8,14-16,18,28H,9-13,17H2,1-3H3
SMILES Code
CC(N1CC2=CC(S(C)(=O)=O)=CC=C2N(S1(=O)=O)CCN3CCC(C4=CNC5=C4C=CC(F)=C5)=CC3)C
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
Shelf Life
>3 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:
Dual 5-HT1B and 5-HT1D antagonist; also 5-HT re-uptake inhibitor.
In vitro activity:
The aim of our study was to examine the effect of LY393558 on the 5-HT-stimulated vasoconstriction of human pulmonary arteries (hPAs) and to determine the underlying mechanism(s). LY393558 showed the greatest antagonistic effect against the vasoconstriction elicited by 5-HT, 5-CT and α-methyl-5-HT.
Reference: Pharmacol Rep. 2020 Jun;72(3):756-762. https://pubmed.ncbi.nlm.nih.gov/32333296/
In vivo activity:
The effect of LY393558, a potent 5-hydroxytryptamine reuptake inhibitor with 5-HT1B/1D receptor antagonist properties, on seizure-induced respiratory arrest evoked by acoustic stimulation was also examined in DBA/1 mice. Acute administration of LY393558 also significantly reduced seizure-induced respiratory arrest in DBA/1 mice.
Reference: Neuroreport. 2019 Aug 14;30(12):842-846. https://pubmed.ncbi.nlm.nih.gov/31283708/
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| Ethanol |
10.0 |
18.29 |
|
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
546.68
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. Baranowska-Kuczko M, Kozłowska H, Schlicker E, Göthert M, MacLean MR, Kozłowski M, Kloza M, Sadowska O, Malinowska B. Reduction of the serotonin 5-HT1B and 5-HT2A receptor-mediated contraction of human pulmonary artery by the combined 5-HT1B receptor antagonist and serotonin transporter inhibitor LY393558. Pharmacol Rep. 2020 Jun;72(3):756-762. doi: 10.1007/s43440-020-00105-2. Epub 2020 Apr 24. PMID: 32333296; PMCID: PMC7329800.
2. Pullar IA, Boot JR, Carney SL, Cohen ML, Colvin EM, Conway RG, Hardy CH, Lucaites VL, Nelson DL, Schenck KW, Tomlinson R, Wedley S. In vitro activity of LY393558, an inhibitor of the 5-hydroxytryptamine transporter with 5-HT(1B/1D/2) receptor antagonist properties. Eur J Pharmacol. 2001 Nov 30;432(1):9-17. doi: 10.1016/s0014-2999(01)01468-6. PMID: 11734182.
3. Chen Q, Tian F, Yue Q, Zhan Q, Wang M, Xiao B, Zeng C. Decreased serotonin synthesis is involved in seizure-induced respiratory arrest in DBA/1 mice. Neuroreport. 2019 Aug 14;30(12):842-846. doi: 10.1097/WNR.0000000000001287. PMID: 31283708.
4. Mitchell SN, Greenslade RG, Cooper J. LY393558, a 5-hydroxytryptamine reuptake inhibitor and 5-HT(1B/1D) receptor antagonist: effects on extracellular levels of 5-hydroxytryptamine in the guinea pig and rat. Eur J Pharmacol. 2001 Nov 30;432(1):19-27. doi: 10.1016/s0014-2999(01)01469-8. PMID: 11734183.
In vitro protocol:
1. Baranowska-Kuczko M, Kozłowska H, Schlicker E, Göthert M, MacLean MR, Kozłowski M, Kloza M, Sadowska O, Malinowska B. Reduction of the serotonin 5-HT1B and 5-HT2A receptor-mediated contraction of human pulmonary artery by the combined 5-HT1B receptor antagonist and serotonin transporter inhibitor LY393558. Pharmacol Rep. 2020 Jun;72(3):756-762. doi: 10.1007/s43440-020-00105-2. Epub 2020 Apr 24. PMID: 32333296; PMCID: PMC7329800.
2. Pullar IA, Boot JR, Carney SL, Cohen ML, Colvin EM, Conway RG, Hardy CH, Lucaites VL, Nelson DL, Schenck KW, Tomlinson R, Wedley S. In vitro activity of LY393558, an inhibitor of the 5-hydroxytryptamine transporter with 5-HT(1B/1D/2) receptor antagonist properties. Eur J Pharmacol. 2001 Nov 30;432(1):9-17. doi: 10.1016/s0014-2999(01)01468-6. PMID: 11734182.
In vivo protocol:
1. Chen Q, Tian F, Yue Q, Zhan Q, Wang M, Xiao B, Zeng C. Decreased serotonin synthesis is involved in seizure-induced respiratory arrest in DBA/1 mice. Neuroreport. 2019 Aug 14;30(12):842-846. doi: 10.1097/WNR.0000000000001287. PMID: 31283708.
2. Mitchell SN, Greenslade RG, Cooper J. LY393558, a 5-hydroxytryptamine reuptake inhibitor and 5-HT(1B/1D) receptor antagonist: effects on extracellular levels of 5-hydroxytryptamine in the guinea pig and rat. Eur J Pharmacol. 2001 Nov 30;432(1):19-27. doi: 10.1016/s0014-2999(01)01469-8. PMID: 11734183.
1: Baranowska-Kuczko M, Kozłowska H, Schlicker E, Göthert M, MacLean MR, Kozłowski M, Kloza M, Sadowska O, Malinowska B. Reduction of the serotonin 5-HT1B and 5-HT2A receptor-mediated contraction of human pulmonary artery by the combined 5-HT1B receptor antagonist and serotonin transporter inhibitor LY393558. Pharmacol Rep. 2020 Jun;72(3):756-762. doi: 10.1007/s43440-020-00105-2. Epub 2020 Apr 24. PMID: 32333296; PMCID: PMC7329800.
2: Chen Q, Tian F, Yue Q, Zhan Q, Wang M, Xiao B, Zeng C. Decreased serotonin synthesis is involved in seizure-induced respiratory arrest in DBA/1 mice. Neuroreport. 2019 Aug 14;30(12):842-846. doi: 10.1097/WNR.0000000000001287. PMID: 31283708.
3: Morecroft I, Pang L, Baranowska M, Nilsen M, Loughlin L, Dempsie Y, Millet C, MacLean MR. In vivo effects of a combined 5-HT1B receptor/SERT antagonist in experimental pulmonary hypertension. Cardiovasc Res. 2010 Feb 1;85(3):593-603. doi: 10.1093/cvr/cvp306. Epub 2009 Sep 7. PMID: 19736308.
4: Morecroft I, Loughlin L, Nilsen M, Colston J, Dempsie Y, Sheward J, Harmar A, MacLean MR. Functional interactions between 5-hydroxytryptamine receptors and the serotonin transporter in pulmonary arteries. J Pharmacol Exp Ther. 2005 May;313(2):539-48. doi: 10.1124/jpet.104.081182. Epub 2005 Jan 19. PMID: 15659538.
5: Mitchell SN, Greenslade RG, Cooper J. LY393558, a 5-hydroxytryptamine reuptake inhibitor and 5-HT(1B/1D) receptor antagonist: effects on extracellular levels of 5-hydroxytryptamine in the guinea pig and rat. Eur J Pharmacol. 2001 Nov 30;432(1):19-27. doi: 10.1016/s0014-2999(01)01469-8. PMID: 11734183.
6: Pullar IA, Boot JR, Carney SL, Cohen ML, Colvin EM, Conway RG, Hardy CH, Lucaites VL, Nelson DL, Schenck KW, Tomlinson R, Wedley S. In vitro activity of LY393558, an inhibitor of the 5-hydroxytryptamine transporter with 5-HT(1B/1D/2) receptor antagonist properties. Eur J Pharmacol. 2001 Nov 30;432(1):9-17. doi: 10.1016/s0014-2999(01)01468-6. PMID: 11734182.
