| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
Somatostatin receptor subtype 2 (sst2). L-054,264 exhibits a Ki of 4 nM for cloned human sst2, with Ki values of 537 nM (sst1), 2480 nM (sst4), 3614 nM (sst3), and 5017 nM (sst5), demonstrating >1000-fold selectivity for sst2 over other somatostatin receptor subtypes.
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|---|---|
| ln Vitro |
L-054,264 shows full agonism on sst2 in the inhibition of forskolin-stimulated accumulation of cAMP with an IC50 of 2 nM. It also demonstrates potent inhibition of growth hormone release in the rat pituitary assay with an IC50 of 6 nM, confirming its functional activity at the sst2 receptor.
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| ln Vivo |
L-054,264 has been reported to inhibit the release of growth hormone in the rat pituitary assay. Additionally, it can be utilized in the study of retinal neuromodulation, indicating its in vivo utility in neuroendocrine and neurosensory contexts, though systemic in vivo efficacy data in disease models remain limited.
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| Enzyme Assay |
For receptor binding assays, membranes from CHO-K1 cells stably expressing cloned human somatostatin receptor subtypes (sst1-5) are incubated with [125I]-LTT-SRIF-28 and varying concentrations of L-054,264 for 60-90 minutes at room temperature in binding buffer (e.g., 50 mM HEPES, pH 7.4, 5 mM MgCl2, 0.5% BSA). Bound radioactivity is separated by filtration through GF/B filters, and specific binding is calculated by subtracting non-specific binding determined in the presence of 1 uM somatostatin-14.
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| Cell Assay |
cAMP inhibition assays: CHO-K1 cells stably expressing human sst2 are seeded in 96-well or 384-well plates for 24 hours. Cells are pre-incubated with increasing concentrations of L-054,264 (0.001 nM to 10 uM) for 30 minutes at 37degC, then stimulated with 10 uM forskolin for an additional 30 minutes. cAMP accumulation is measured using a homogeneous time-resolved fluorescence (HTRF) cAMP kit. EC50 values for inhibition of forskolin-stimulated cAMP accumulation are calculated by non-linear regression.
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| Animal Protocol |
For growth hormone release studies, rat pituitary cells are isolated and cultured, then pre-incubated with L-054,264 at varying concentrations for 30-60 minutes before stimulation with growth hormone-releasing hormone (GHRH). GH levels in the supernatant are measured by radioimmunoassay (RIA) or ELISA. For a typical pharmacodynamic study in rodents, L-054,264 is administered orally (1-10 mg/kg) or intravenously (0.1-1 mg/kg). Plasma growth hormone levels are measured at baseline and at several post-dose time points (e.g., 1, 2, 4, 8 hours) via ELISA to assess the suppression of GH secretion.
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| ADME/Pharmacokinetics |
L-054,264 is orally bioavailable with an acceptable pharmacokinetic profile. Following oral administration, it reaches peak plasma concentrations within 1-2 hours. Based on its small molecule structure (MW 539.7), it is expected to have moderate clearance and a half-life suitable for once-daily dosing in preclinical species. In vitro metabolic stability can be assessed using liver microsome assays from various species. Reported solubility: <26.99 mg/ml in DMSO; <53.97 mg/ml in ethanol.
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| Toxicity/Toxicokinetics |
Specific toxicity data for L-054,264 are not widely reported in the literature. As a research compound with high selectivity for the sst2 receptor, standard safety assessments would include in vitro cytotoxicity assays (e.g., MTT in HEK293 cells) and cardiovascular safety profiling (e.g., hERG channel inhibition). No significant adverse events have been published for this compound at standard research doses.
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| References |
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| Additional Infomation |
Other information: L-054,264 is a research-grade chemical and is not FDA-approved for clinical use. It has been utilized as a selective pharmacological tool to probe the functions of sst2 in somatostatin-mediated signaling. Its binding selectivity and agonistic properties make it a valuable agent for target validation studies, with emerging applications in cancer biology, endocrinology, and retinal neuromodulation research. Cryo-EM structures of SSTR2-Gi1 complexes with L-054,264 bound have been resolved, providing detailed molecular insights into its activation mechanism.
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| Molecular Formula |
C33H41N5O2
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|---|---|
| Molecular Weight |
539.71
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| Exact Mass |
539.326
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| CAS # |
208706-12-1
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| PubChem CID |
9915239
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
6.15
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
40
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| Complexity |
915
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| Defined Atom Stereocenter Count |
3
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| SMILES |
NC[C@@H]1C[C@H](CNC([C@H](NC(N2CCC3(C4=CC=CC=C4C=C3)CC2)=O)CC2C3=CC=CC=C3NC=2)=O)CCC1
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| InChi Key |
DAMXHAMKVXERLM-FVBCXUTKSA-N
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| InChi Code |
InChI=1S/C33H41N5O2/c34-20-23-6-5-7-24(18-23)21-36-31(39)30(19-26-22-35-29-11-4-2-9-27(26)29)37-32(40)38-16-14-33(15-17-38)13-12-25-8-1-3-10-28(25)33/h1-4,8-13,22-24,30,35H,5-7,14-21,34H2,(H,36,39)(H,37,40)/t23-,24+,30+/m0/s1
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| Chemical Name |
N-[(2R)-1-[[(1R,3S)-3-(aminomethyl)cyclohexyl]methylamino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]spiro[indene-1,4'-piperidine]-1'-carboxamide
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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) |
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
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|---|---|
| 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
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] 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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8528 mL | 9.2642 mL | 18.5285 mL | |
| 5 mM | 0.3706 mL | 1.8528 mL | 3.7057 mL | |
| 10 mM | 0.1853 mL | 0.9264 mL | 1.8528 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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