HT-2157 (also known as SNAP 37889) is a selective, high-affinity, and competitive antagonists of galanin-3 receptor (Gal3) that has the potential for the treatment of major depressive disorder. Administering SNAP 37889 or its more soluble analog, SNAP 398299, acutely improved the social interaction of rats. Acute SNAP 37889 has also been demonstrated to decrease guinea pig vocalizations following mother separation, lessen stress-induced hyperthermia in mice, increase punished drinking in rats, and reduce immobility and lengthen swimming times in rats during forced swim tests. Additionally, following a 14-day treatment period, SNAP 37889 prolonged social interaction times and continued to have antidepressant effects in forced swim tests with rats after a 21-day treatment period. In microdialysis studies, SNAP 37889 partially antagonized the galanin-evoked reduction in hippocampal serotonin (5-hydroxytryptamine, 5-HT), as did the 5-HT(1A) receptor antagonist WAY100635.

Physicochemical Properties

Molecular Formula	C21H13F3N2O
Molecular Weight	366.34
Exact Mass	366.098
Elemental Analysis	C, 68.85; H, 3.58; F, 15.56; N, 7.65; O, 4.37
CAS #	303149-14-6
Related CAS #	303149-14-6
PubChem CID	1471834
Appearance	Yellow to orange solid powder
LogP	5.569
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	2
Heavy Atom Count	27
Complexity	583
Defined Atom Stereocenter Count	0
SMILES	O=C1N(C2=CC=CC=C2)C3=C(C=CC=C3)/C1=N/C4=CC=CC(C(F)(F)F)=C4
InChi Key	TXCGMRVPXUBHAL-UHFFFAOYSA-N
InChi Code	InChI=1S/C21H13F3N2O/c22-21(23,24)14-7-6-8-15(13-14)25-19-17-11-4-5-12-18(17)26(20(19)27)16-9-2-1-3-10-16/h1-13H
Chemical Name	1-phenyl-3-[3-(trifluoromethyl)phenyl]iminoindol-2-one
Synonyms	HT-2157; HT2157; HT 2157; SNAP37889; SNAP 37889; SNAP-37889
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 (e.g. under nitrogen), 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	Galanin-3 receptor
ln Vitro	In vitro activity: HT-2157 (SNAP 37889) is highly selective for Gal3 over the Gal1 and Gal2 subtypes (Ki>10,000 nM for each subtype; n=46 of each subtype), and binds with high affinity to membranes from transiently transfected LMTK- cells expressing the human Gal3 receptor (Ki=17.44±0.01 nM; n>100). When tested for the antagonism of galanin-evoked inhibition of adenylyl cyclase, HT-2157 (0.1-10 μM) produces concentration-dependent rightward shifts of the concentration-effect curve to galanin[1].
ln Vivo	In rats who prefer alcohol, the galanin-3 receptor antagonist HT-2157 (SNAP 37889) decreases operant responding for ethanol. In the iP (alcohol-preferring) rat, the novel selective GALR3 antagonist HT-2157 is used to decrease anxiety-like behavior and voluntary ethanol consumption. In either the light-dark or elevated plus maze paradigms, male intraperitoneal rats treated with HT-2157 at a dose of 30 mg/kg (i.p.) do not exhibit changes in anxiety-like behavior or altered locomotor activity. Operant responding for solutions containing ethanol, sucrose, and saccharin is decreased when HT-2157 (30 mg/kg, i.p.) is administered. The current study's overall findings demonstrate that HT-2157 (30 mg/kg, i.p.) is useful in lowering operant responding to ethanol[2].
Enzyme Assay	The 125I-galanin displacement assay is used to determine the binding affinities for HT-2157 (SNAP 37889) and SNAP 398299 at the human Gal1, Gal2, and Gal3 receptors. Furthermore, is examined for binding in a wide panel of cross-reactivity components, such as ion channels, transporters, enzymes, and G-protein-coupled receptors. The ability of HT-2157 to antagonize functional responses to galanin is examined in modified HEK-293 cells (PEAKrapid cells) transiently cotransfected with the Gal3 receptor and Gαz by measuring the inhibition of adenylyl cyclase activity[1].
Animal Protocol	Rats: The effect of HT-2157 on locomotor activity is examined using adult male iP rats (n=12; 418-467 g). To make sure that any future changes in anxiety or ethanol consumption are not the result of the drug's sedative properties, locomotor activity is tested. The rats undergo three consecutive days of 60-minute sessions to acclimate to the locomotor cells (26 x 26 x 40 cm). Rats are split into two even groups and given a single injection of either HT-2157 (30 mg/kg, i.p.) or vehicle (1 ml/kg, i.p.) 30 min before they were placed in the locomotor cells for a 60-minute session in order to minimize the effect of habituation during the treatment phase. The treatments are switched around the next day, giving each rat treatment with both the vehicle and the SNAP 37889 compound. The TruScan 2.0 program automatically records movements in terms of the total distance traveled (cm), the number of moves, and the move time (s).
References	[1]. Anxiolytic- and antidepressant-like profiles of the galanin-3 receptor (Gal3) antagonists SNAP 37889 and SNAP 398299. Proc Natl Acad Sci U S A. 2005 Nov 29;102(48):17489-94. [2]. The galanin-3 receptor antagonist, SNAP 37889, reduces operant responding for ethanol in alcohol-preferring rats. Regul Pept. 2011 Jan 17;166(1-3):59-67.

Solubility Data

Solubility (In Vitro)

DMSO: ≥ 29 mg/mL (~79.2 mM) Water: < 1 mg/mL Ethanol: < 1 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.82 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 25.0 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: ≥ 2.5 mg/mL (6.82 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 25.0 mg/mL clear DMSO stock solution to 900 μL of 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	2.7297 mL	13.6485 mL	27.2970 mL
	5 mM	0.5459 mL	2.7297 mL	5.4594 mL
	10 mM	0.2730 mL	1.3649 mL	2.7297 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.