PeptideDB

SNAP 398299 903878-06-8

SNAP 398299 903878-06-8

CAS No.: 903878-06-8

SNAP-398299 (also known as SNAP398299), a more water soluble analog of HT-2157 (SNAP 37889), is a selective, high-affini
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SNAP-398299 (also known as SNAP398299), a more water soluble analog of HT-2157 (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. Acute administration of SNAP 37889 or SNAP 398299 enhanced rat social interaction. Furthermore, acute SNAP 37889 was also shown to reduce guinea pig vocalizations after maternal separation, to attenuate stress-induced hyperthermia in mice, to increase punished drinking in rats, and to decrease immobility and increase swimming time during forced swim tests with rats. Moreover, SNAP 37889 increased the social interaction time after 14 days of treatment and maintained its antidepressant effects during forced swim tests with rats after 21 days of treatment. 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 C27H24F3N3O2
Molecular Weight 479.5
Exact Mass 479.182
CAS # 903878-06-8
Related CAS #
903878-06-8
PubChem CID 11698643
Appearance Typically exists as solid at room temperature
Density 1.30±0.1 g/cm3(Predicted)
Boiling Point 610.4±65.0 °C(Predicted)
LogP 5.7
Hydrogen Bond Donor Count 0
Hydrogen Bond Acceptor Count 7
Rotatable Bond Count 6
Heavy Atom Count 35
Complexity 767
Defined Atom Stereocenter Count 0
SMILES

N1(C2=CC=CC(OCCN3CCCC3)=C2)C2=C(C=CC=C2)C(=NC2=CC=CC(C(F)(F)F)=C2)C1=O

InChi Key HXCJZIBJTFITNI-UHFFFAOYSA-N
InChi Code

InChI=1S/C27H24F3N3O2/c28-27(29,30)19-7-5-8-20(17-19)31-25-23-11-1-2-12-24(23)33(26(25)34)21-9-6-10-22(18-21)35-16-15-32-13-3-4-14-32/h1-2,5-12,17-18H,3-4,13-16H2
Chemical Name

1-[3-(2-pyrrolidin-1-ylethoxy)phenyl]-3-[3-(trifluoromethyl)phenyl]iminoindol-2-one
Synonyms

SNAP 398299; SNAP398299; SNAP-398299; HT-2157 analog
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

In vitro activity: SNAP-398299 (also known as SNAP398299), a more water soluble analog of HT-2157 (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. Acute administration of SNAP 37889 or SNAP 398299 enhanced rat social interaction. Furthermore, acute SNAP 37889 was also shown to reduce guinea pig vocalizations after maternal separation, to attenuate stress-induced hyperthermia in mice, to increase punished drinking in rats, and to decrease immobility and increase swimming time during forced swim tests with rats. Moreover, SNAP 37889 increased the social interaction time after 14 days of treatment and maintained its antidepressant effects during forced swim tests with rats after 21 days of treatment. 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.


Kinase Assay: Binding affinities for HT-2157 (SNAP 37889) and SNAP 398299 at the human Gal1, Gal2, and Gal3 receptors are determined by using the 125I-galanin displacement assay. Additionally, is tested for binding in a broad cross-reactivity panel that included G-protein-coupled receptors, ion channels, enzymes, and transporters. 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.


Cell Assay: HT-2157 (SNAP 37889) binds with high affinity to membranes from transiently transfected LMTK- cells expressing the human Gal3 receptor (Ki=17.44±0.01 nM; n>100) and is highly selective for Gal3 over the Gal1 and Gal2 subtypes (Ki>10,000 nM for each subtype; n=46 of each subtype). 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.

ln Vivo
The galanin-3 receptor antagonist, HT-2157 (SNAP 37889), reduces operant responding for ethanol in alcohol-preferring rats. The novel selective GALR3 antagonist, HT-2157, to reduce anxiety-like behaviour and voluntary ethanol consumption in the iP (alcohol-preferring) rat. Male iP rats treated with HT-2157 at a dose of 30 mg/kg (i.p.) do not show altered locomotor activity or changes in anxiety-like behaviour in the elevated plus maze or light-dark paradigms. Treatment with HT-2157 (30 mg/kg, i.p.) reduces operant responding for solutions containing ethanol, sucrose and saccharin. Collectively, results from the current study shows that HT-2157 (30 mg/kg, i.p.) is effective in reducing operant responding for ethanol, independent of a sedative effect.
Animal Protocol
30 mg/kg, i.p
Rats
References :Proc Natl Acad Sci U S A.2005 Nov 29;102(48):17489-94;Regul Pept.2011 Jan 17;166(1-3):59-67.

Solubility Data


Solubility (In Vitro)
DMSO:≥ 30 mg/mL
Water:N/A
Ethanol:N/A
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 2.0855 mL 10.4275 mL 20.8551 mL
5 mM 0.4171 mL 2.0855 mL 4.1710 mL
10 mM 0.2086 mL 1.0428 mL 2.0855 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.