YS-49 (monohydrate) is an activator of PI3K/Akt (a downstream target of RhoA) and reduces RhoA/PTEN activation in 3-methylcholine-treated cells. YS-49 can inhibit angiotensin II (Ang II)-stimulated VSMC cell proliferation/growth by inducing heme oxygenase (HO-1). YS-49 is an isoquinoline compound alkaloid that has strong positive inotropic effects due to its ability to activate cardiac β-adrenoceptors.

Physicochemical Properties

Molecular Formula	C20H22BRNO3
Molecular Weight	404.3
CAS #	3028631-24-2
Related CAS #	YS-49;132836-42-1
Appearance	Off-white to gray solid powder
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	PI3K/Akt[3]
ln Vitro	In both RAVSMC and RAW 264.7 cells exposed to lipopolysaccharide (LPS) plus INF-γ, YS-49 (1–100 μM; 18 hours) concentration-dependently reduces the buildup of nitrite, with IC50 values of 22 μM and 30 μM, respectively[2]. In RAVSMC and RAW 264.7 cells, YS-49 (10–100 μM; 18 hours) inhibits the transcriptional level of the iNOS gene expression that is triggered by LPS and/or cytokines[2].
ln Vivo	Treatment with YS-49 (5 mg/kg; intraperitoneal injection; 8 hours; male Sprague Dawley rats) dramatically lowers blood NOx levels in animals treated with lipopolysaccharide (LPS); NOx levels drop from 86 μM to 34 μM[2].
Cell Assay	Cell Viability Assay[2] Cell Types: RAVSMC and RAW 264.7 cells Tested Concentrations: 10 μM, 30 μM and 100 μM(RAVSMC); 1 μM, 10 μM and 100 μM(RAW 264.7) Incubation Duration: 18 hrs (hours) Experimental Results: Inhibited the Accumulation of nitrite in both RAVSMC and RAW 264.7 exposed to LPS+INF-γ, with IC50 values of 22 and 30 μM, respectively. Western Blot Analysis[2] Cell Types: RAVSMC and RAW 264.7 cells Tested Concentrations: 10 μM, 30 μM and 100 μM Incubation Duration: 18 hrs (hours) Experimental Results: Concentration-dependently inhibited the expression of iNOS protein induced by LPS plus IFN-γ.
Animal Protocol	Animal/Disease Models: Male Sprague Dawley rats (250-300 g)[2] Doses: 5 mg/kg Route of Administration: intraperitoneal (ip)injection; 8 hrs (hours) Experimental Results: Serum NOx levels were Dramatically decreased.
References	[1]. YS 49, 1-(alpha-naphtylmethyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, regulates angiotensin II-stimulated ROS production, JNK phosphorylation and vascular smooth muscle cell proliferation via the induction of heme oxygenase-1. Life Sci. 2008 Mar 12;82(11-12):600-7. [2]. Prevention of the expression of inducible nitric oxide synthase by a novel positive inotropic agent, YS 49, in rat vascular smooth muscle and RAW 264.7 macrophages. Br J Pharmacol. 1999 Sep;128(2):357-64. [3]. RhoA-mediated inhibition of vascular endothelial cell mobility: positive feedback through reduced cytosolic p21 and p27. J Cell Physiol. 2014 Oct;229(10):1455-65.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.4734 mL	12.3671 mL	24.7341 mL
	5 mM	0.4947 mL	2.4734 mL	4.9468 mL
	10 mM	0.2473 mL	1.2367 mL	2.4734 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.