U-74389G (PNU74389G meleate) is an antioxidant that can inhibit lipid peroxidation. U-74389G can protect against ischemia-reperfusion injury and is extensively used in animal models of ischemic injury and hypertension with anti-inflammatory activity.

Physicochemical Properties

Molecular Formula	C41H54N6O6
Molecular Weight	726.90
Exact Mass	726.41
CAS #	153190-29-5
PubChem CID	9896684
Appearance	White to off-white solid powder
Boiling Point	811.6ºC at 760 mmHg
Flash Point	444.6ºC
Vapour Pressure	2.12E-26mmHg at 25°C
LogP	5.057
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	12
Rotatable Bond Count	8
Heavy Atom Count	53
Complexity	1380
Defined Atom Stereocenter Count	5
SMILES	C[C@@]12C=CC(=O)C=C2CC[C@H]3[C@@H]4CC[C@H](C(=O)CN5CCN(CC5)C6=NC(=NC(=C6)N7CCCC7)N8CCCC8)[C@@]4(C)CC=C31.C(=C/C(=O)O)/C(=O)O
InChi Key	ABCSSKWSUJMJCP-WQDFMEOSSA-N
InChi Code	InChI=1S/C37H50N6O2.C4H4O4/c1-36-13-11-27(44)23-26(36)7-8-28-29-9-10-31(37(29,2)14-12-30(28)36)32(45)25-40-19-21-42(22-20-40)34-24-33(41-15-3-4-16-41)38-35(39-34)43-17-5-6-18-43;5-3(6)1-2-4(7)8/h11-13,23-24,28-29,31H,3-10,14-22,25H2,1-2H3;1-2H,(H,5,6)(H,7,8)/b;2-1-/t28-,29-,31+,36-,37-;/m0./s1
Chemical Name	(Z)-but-2-enedioic acid;(8S,10S,13S,14S,17S)-17-[2-[4-(2,6-dipyrrolidin-1-ylpyrimidin-4-yl)piperazin-1-yl]acetyl]-10,13-dimethyl-6,7,8,12,14,15,16,17-octahydrocyclopenta[a]phenanthren-3-one
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

ln Vitro	In endotoxin-stimulated peritoneal macrophages, U-74389G (12.5, 25 and 50 μM; 24 h) suppresses the formation of nitrite[3].
ln Vivo	Significant anti-inflammatory efficacy is demonstrated by U-74389G (intravenous injection; 10 mg/kg; once daily; 6 d) treatment, which can lower colonic TNF-α, improve CMDI score, and enhance weight change[2]. The administration of U-74389G (intravenous injection; 15 or 30 mg/kg) provides substantial protection against lethality induced by lipopolysaccharide, lowers plasma nitrite levels, improves liver function, lowers hypotension, brings aortic ring hyporeactivity back to control levels, and inhibits the activity of inducible NO synthase in the liver and aorta[3].
Cell Assay	Cell Viability Assay[3] Cell Types: Peritoneal macrophages Tested Concentrations: 12.5, 25 and 50 μM Incubation Duration: 24 hrs (hours) Experimental Results: diminished the nitrite concentrations in the supernatants of LPS-primed macrophages in a dose-dependent manner.
Animal Protocol	Animal/Disease Models: Rat model of trinitrobenzenesulfonic acid-induced colitis[2] Doses: 10 mg/kg Route of Administration: intravenous (iv) injection; 10 mg/kg; one time/day; 6 d Experimental Results: decreased TNF -α, the macroscopic index of mucosal damage score (CMDI) and increased body weight. Animal/Disease Models: Male Sprague–Dawley rats injected with Lipopolysaccharide[3] Doses: 15 or 30 mg/kg Route of Administration: intravenous (iv) injection; 15 or 30 mg/ kg Experimental Results: Protected against lipopolysaccharide-induced lethality (90% survival rate 24 h and 80% 72 h after Lipopolysaccharide injection, respectively, following the highest dose).
References	[1]. A M Perna, et al. Protection of rat heart from ischaemia-reperfusion injury by the 21-aminosteroid U-74389G. Pharmacol Res. 1996 Jul-Aug;34(1-2):25-31. [2]. Georgios Antonios Margonis, et al. Effectiveness of sildenafil and U-74389G in a rat model of colitis. J Surg Res. 2015 Feb;193(2):667-74. [3]. D Altavilla, et al. The lazaroid, U-74389G, inhibits inducible nitric oxide synthase activity, reverses vascular failure and protects against endotoxin shock. Eur J Pharmacol. 1999 Mar 12;369(1):49-55.

Solubility Data

Solubility (In Vitro)

DMSO: 100 mg/mL (137.57 mM)

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	1.3757 mL	6.8785 mL	13.7571 mL
	5 mM	0.2751 mL	1.3757 mL	2.7514 mL
	10 mM	0.1376 mL	0.6879 mL	1.3757 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.