NTU281 is a potent inhibitor of transglutaminase-2. NTU281 can reduce the increase in serum creatinine and proteinuria in diabetic rats. NTU281 can also reduce glomerular type I collagen accumulation, Hic-5 and α-SMA expression, and reduce apoptosis. NTU281 may be utilized to study diabetes-induced glomerulosclerosis.

Physicochemical Properties

Molecular Formula	C25H31N2O6S
Molecular Weight	487.59
Exact Mass	487.19
CAS #	815619-12-6
PubChem CID	11433028
Appearance	Typically exists as solid at room temperature
LogP	3.1
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	14
Heavy Atom Count	34
Complexity	674
Defined Atom Stereocenter Count	2
SMILES	C[S+](C)CC(=O)CC[C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)OCC2=CC=CC=C2
InChi Key	MQKDBWQFOOQINN-VXKWHMMOSA-O
InChi Code	InChI=1S/C25H30N2O6S/c1-34(2)17-20(28)13-14-21(24(30)31)26-23(29)22(15-18-9-5-3-6-10-18)27-25(32)33-16-19-11-7-4-8-12-19/h3-12,21-22H,13-17H2,1-2H3,(H2-,26,27,29,30,31,32)/p+1/t21-,22-/m0/s1
Chemical Name	[(5S)-5-carboxy-2-oxo-5-[[(2S)-3-phenyl-2-(phenylmethoxycarbonylamino)propanoyl]amino]pentyl]-dimethylsulfanium
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
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 Vivo	NTU281 (2.5 μl/h, 50 mM; administered to the kidney via cannula) decreases the overexpression of glomerular type I collagen and increases the expression of glomerular Hic-5 and α-SMA. It also lessens albuminuria, glomerulosclerosis, tubulointerstitial scarring, serum creatinine, and albuminuria [1][2].
Animal Protocol	Animal/Disease Models: Male Wistar Han rat [right uninephrectomy followed by tail vein injection of streptozotocin (35 mg/kg, citrate buffer pH 4) to induce hyperglycemia][1] Doses: 2.5 μl/h 50 mM Route of Administration: Intubation to delivery to kidney Experimental Results: diminished glomerular type I collagen overexpression by approximately 50%; diminished glomerular Hic-5 expression; diminished α-SMA expression induced by diabetic nephropathy . Animal/Disease Models: Male Wistar Han rat [right uninephrectomy followed by tail vein injection of streptozotocin (35 mg/kg, citrate buffer pH 4) to induce hyperglycemia][2] Doses: different concentrations Mode of Route of Administration: Delivered to the kidneys by cannula. Experimental Results: During the eight-month experimental period, Dramatically diminished the increase in serum creatinine (-68%) and proteinuria (-80%) in diabetic rats; due to collagen I, III and IV accumulation was diminished, glomerulosclerosis (-76.6%) and tubulointerstitial scarring (-68.2%) were diminished; myofibroblast number was diminished
References	[1]. Inhibition of collagen I accumulation reduces glomerulosclerosis by a Hic-5-dependent mechanism in experimental diabetic nephropathy. Lab Invest. 2013 May;93(5):553-65. [2]. Do changes in transglutaminase activity alter latent transforming growth factor beta activation in experimental diabetic nephropathy? Nephrol Dial Transplant. 2010 Dec;25(12):3897-910.

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	2.0509 mL	10.2545 mL	20.5090 mL
	5 mM	0.4102 mL	2.0509 mL	4.1018 mL
	10 mM	0.2051 mL	1.0255 mL	2.0509 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.