| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
IC50: 0.58 nM (SERT)[1]
SERT (serotonin transporter). SERT-IN-2 inhibits the reuptake of serotonin from the synaptic cleft, increasing extracellular serotonin levels and enhancing serotonergic neurotransmission in the brain. |
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| ln Vitro |
SERT-IN-2 is a potent SERT inhibitor with an IC50 of 0.58 nM. It shows good bioavailability of 83.28% in rats and can cross the blood-brain barrier. At doses of 1-10 mg/kg, SERT-IN-2 inhibits serotonin uptake and potently antagonizes p-chloroamphetamine (PCA)-induced depletion of 5-HT in the rat hypothalamus, confirming SERT target engagement in vivo.
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| ln Vivo |
In rats and dogs, SERT-IN-2 (DH4) (2.5 mg/kg, 5 mg/kg; intravenous or oral; single dosage) has high oral bioavailability and plasma exposure [1]. The blood-brain barrier can be crossed by SERT-IN-2 (10 mg/kg; intraperitoneal injection; single dosage) in SD rats [1]. In the rat hypothalamus, SERT-IN-2 (1–10 mg/kg; i.p.; single dosage) effectively counteracts p-chloroamphetamine (PCA)-induced serotonin depletion by inhibiting serotonin uptake [1]. Rats treated with SERT-IN-2 (1–10 mg/kg; intravenous injection; three times prior to the test) exhibit antidepressant effects, and the number of immobilities in the forced swim test (FST) decreases dose-dependently [1]. Pharmacokinetic analysis[1] Rat IV 1 193 1340 7.53 6.41 11.6 / PO 2.5 180 2790 7.28 / 83.28 Dog IV 1 520 2820 4.39 3.4 5.14 / PO 5 794 7540 16.4 / / 53.5 Route Dose (mg/kg) Cmax (ng/mL) AUC(0-t) (ng·h/mL) T1/2 (h) Vss (L/kg) Cl (L/h/kg) F (%)
SERT-IN-2 exerts antidepressant effects in the rat forced swimming test (FST). At doses of 1-10 mg/kg administered intravenously (three times before testing), SERT-IN-2 reduces immobility times in a dose-dependent manner, indicating antidepressant-like activity. At 2.5 mg/kg and 5 mg/kg oral doses, SERT-IN-2 shows high plasma exposure and oral bioavailability in dogs and rats. At 10 mg/kg intraperitoneal, it crosses the blood-brain barrier in SD rats. |
| Enzyme Assay |
SERT binding assays: Human SERT-expressing HEK293 cell membranes (10-20 ug) are incubated with [3H]-paroxetine (0.5 nM) and increasing concentrations of SERT-IN-2 (0.001-1000 nM) in 50 mM Tris-HCl, pH 7.4, 150 mM NaCl, 5 mM KCl for 60 min at 25degC. Bound radioactivity is separated by GF/B filtration. Non-specific binding is determined with 10 uM fluoxetine. IC50 values are calculated by nonlinear regression. The reported IC50 is 0.58 nM.
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| Cell Assay |
Human SERT-expressing HEK293 cells are seeded in 24-well plates for 24 hours. Cells are pre-incubated with increasing concentrations of SERT-IN-2 (0.01-1000 nM) for 15 min, then incubated with [3H]-5-HT (50-100 nM) for 5-10 min at 37degC. Uptake is terminated by aspiration and washing with ice-cold buffer. Cells are lysed, and incorporated radioactivity is measured by liquid scintillation counting. IC50 is determined from inhibition curves. For selectivity assessment, assays for NET and DAT are performed similarly using [3H]-NE and [3H]-DA as substrates.
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| Animal Protocol |
For PK studies in rats: SERT-IN-2 is administered intravenously (1 mg/kg) or orally (2.5 mg/kg). Blood samples are collected at 0.083, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24 hours. Plasma is analyzed by LC-MS/MS. For brain penetration assessment, SERT-IN-2 (10 mg/kg, i.p.) is administered to SD rats, and brain homogenates are analyzed at 0.5-4 hours post-dose. For pharmacodynamics, the PCA-induced 5-HT depletion model is used: SERT-IN-2 is administered 30 min before PCA (5 mg/kg, i.p.), and hypothalamic 5-HT levels are measured by HPLC-ECD 2 hours later. For antidepressant efficacy, the forced swimming test (FST) is performed following i.v. administration.
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| ADME/Pharmacokinetics |
PK parameters (rat): IV (1 mg/kg): Cmax 193 ng/mL, AUC(0-t) 1340 ngh/mL, t1/2 7.53 h, Vss 6.41 L/kg, Cl 11.6 L/h/kg. PO (2.5 mg/kg): Cmax 180 ng/mL, AUC(0-t) 2790 ngh/mL, t1/2 7.28 h, F = 83.28%. Dog PK: IV (1 mg/kg): Cmax 520 ng/mL, AUC 2820 ngh/mL, t1/2 4.39 h, Vss 3.4 L/kg, Cl 5.14 L/h/kg. PO (5 mg/kg): Cmax 794 ng/mL, AUC 7540 ngh/mL, t1/2 16.4 h, F = 53.5%. SERT-IN-2 crosses BBB (brain penetration confirmed).
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| Toxicity/Toxicokinetics |
No specific toxicity data are reported for SERT-IN-2. As a potent SERT inhibitor with antidepressant activity, the safety profile would likely resemble that of SSRI-class antidepressants, including potential for gastrointestinal disturbances (nausea, diarrhea), sexual dysfunction, weight gain, and serotonin syndrome at high doses or in combination with other serotonergic agents. Standard toxicology studies (Ames test, hERG, repeat-dose toxicity in rodents) would be required for preclinical development. No clinical trials have been conducted.
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| References | |
| Additional Infomation |
Other information: SERT-IN-2 is a research compound not approved by the FDA. The molecular formula is C26H24F2N6 with molecular weight 458.51. Purity ≥98%. Storage: at -20degC, shipped on dry ice. Solubility: DMSO 200 mg/mL. Canonical SMILES: N#CC1=CC2=C(NC=C2CCCN3CCN(CC3)C4=NC=C(C5=CC=C(C=C5F)F)C=N4)C=C1. It is for research use only and not for therapeutic applications.
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| Molecular Formula |
C26H24F2N6
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|---|---|
| Molecular Weight |
458.505771636963
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| Exact Mass |
458.203
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| CAS # |
2055228-33-4
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| PubChem CID |
124121272
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| Appearance |
White to off-white solid powder
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| LogP |
4.5
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
34
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| Complexity |
699
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N1C2=C(C=C(C#N)C=C2)C(CCCN2CCN(C3=NC=C(C4=CC=C(F)C=C4F)C=N3)CC2)=C1
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| InChi Key |
MONCKXMZFAXBAZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H24F2N6/c27-21-4-5-22(24(28)13-21)20-16-31-26(32-17-20)34-10-8-33(9-11-34)7-1-2-19-15-30-25-6-3-18(14-29)12-23(19)25/h3-6,12-13,15-17,30H,1-2,7-11H2
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| Chemical Name |
3-[3-[4-[5-(2,4-difluorophenyl)pyrimidin-2-yl]piperazin-1-yl]propyl]-1H-indole-5-carbonitrile
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO: 200 mg/mL (436.20 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (10.90 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 50.0 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: ≥ 5 mg/mL (10.90 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 50.0 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 | 2.1810 mL | 10.9049 mL | 21.8098 mL | |
| 5 mM | 0.4362 mL | 2.1810 mL | 4.3620 mL | |
| 10 mM | 0.2181 mL | 1.0905 mL | 2.1810 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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