L-732138 is a selective and competitive neurokinin-1 (NK-1) receptor blocker (antagonist) with IC50 of 2.3 nM. L-732138 is 200-fold more potent at the cloned human NK-1 receptor than at the cloned rat NK-1 receptor and more than 1000-fold more potent than at the human NK-2 and NK-3 receptors. L-732138 reduces hyperalgesia and Has potential anticancer/anti-tumor effects.

Physicochemical Properties

Molecular Formula	C22H18F6N2O3
Molecular Weight	472.39
Exact Mass	472.122
CAS #	148451-96-1
PubChem CID	132837
Appearance	White to off-white solid powder
Melting Point	147-148 ℃(lit.)
LogP	5.387
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	9
Rotatable Bond Count	7
Heavy Atom Count	33
Complexity	677
Defined Atom Stereocenter Count	1
SMILES	CC(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)OCC3=CC(=CC(=C3)C(F)(F)F)C(F)(F)F
InChi Key	BYYQYXVAWXAYQC-IBGZPJMESA-N
InChi Code	InChI=1S/C22H18F6N2O3/c1-12(31)30-19(8-14-10-29-18-5-3-2-4-17(14)18)20(32)33-11-13-6-15(21(23,24)25)9-16(7-13)22(26,27)28/h2-7,9-10,19,29H,8,11H2,1H3,(H,30,31)/t19-/m0/s1
Chemical Name	[3,5-bis(trifluoromethyl)phenyl]methyl (2S)-2-acetamido-3-(1H-indol-3-yl)propanoate
Synonyms	L 732138; L732138; 3,5-bis(TFM)Bz NAcTrp
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 Vitro	Cytotoxicity is concentration-dependent and is produced in COLO 858, MEL HO, and COLO 679 cells treated with L-732138 (0 -100 µM; initial doubling time). With an IC50 of 44.6 μM in COLO 858 cells, 76.3 μM in MEL HO cells, and 64.2 μM in COLO 679 cells, L-732138 suppresses cell growth. Substance P (SP) mitogen stimulation is blocked by L-732138 [1]. Following L-732,138 treatment, a significant number of apoptotic cells were discovered in the melanoma cell lines COLO 858, MEL HO, and COLO 679. Three melanoma cell lines had an IC50 concentration of 43.6% apoptotic cells in DAPI-stained cultures, and an IC100 concentration of 51.4% apoptotic cells [1].
ln Vivo	Vagus nerve-induced plasma extravasation was eliminated and LPS enhancement was markedly decreased in male Dunkin-Hartley guinea pigs treated with L-732138 (10-4-10-2 mol/kg; intravenous injection; 15 min duration). LPS-enhanced vagus nerve-induced plasma extravasation cannot be fully inhibited by L-732138 or SOD administration alone, but it can be blocked by the combination of the two pretreatments [3].
Cell Assay	Cell Proliferation Assay[1] Cell Types: COLO 858, MEL HO and COLO 679 Cell Tested Concentrations: 0 µM, 20 µM, 40 µM, 60 µM, 80 µM, 100 µM Incubation Duration: First Doubling Time Experimental Results: Produced Concentration - dependent cytotoxicity.
Animal Protocol	Animal/Disease Models: Male Dunkin-Hartley guinea pigs (350-500 g) injected with lipopolysaccharide (LPS) [3] Doses: 10-4 mol/kg, 10-3 mol/kg and 10-2 mol/kg Route of Administration: intravenous (iv) (iv)Injection Injection; 15 min Experimental Results: Eliminates vagus nerve-induced plasma leakage in tracheobronchial tissue and dose-dependently inhibits vagus nerve-induced plasma leakage in LPS-enhanced tracheobronchial tissue.
References	[1]. The NK-1 Receptor Antagonist L-732,138 Induces Apoptosis and Counteracts Substance P-Related Mitogenesis in Human Melanoma Cell Lines. Cancers (Basel). 2010 Apr 20;2(2):611-23. [2]. Characterization of the interaction of N-acyl-L-tryptophan benzyl ester neurokinin antagonists with the human neurokinin-1 receptor. J Biol Chem. 1994 Mar 4;269(9):6587-91. [3]. Lipopolysaccharide enhances neurogenic plasma exudation in guinea-pig airways. Br J Pharmacol. 1998 Oct;125(4):711-6.

Solubility Data

Solubility (In Vitro)

DMSO : ~250 mg/mL (~529.23 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 6.25 mg/mL (13.23 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 62.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 6.25 mg/mL (13.23 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 62.5 mg/mL clear DMSO stock solution to 900 μL corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.1169 mL	10.5845 mL	21.1689 mL
	5 mM	0.4234 mL	2.1169 mL	4.2338 mL
	10 mM	0.2117 mL	1.0584 mL	2.1169 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.