| ln Vitro |
SH-11037 (14a) effectively and selectively inhibits the proliferation of human retinal microvascular endothelial cells (HRECs), with a GI50 value of 0.055 μM. The selectivity for HUVECs is approximately 14-fold, the selectivity for 92-1 cells is greater than 1000-fold, and the selectivity for Y79 cells is approximately 218-fold [1]. SH-11037 inhibits the proliferation of human retinal microvascular endothelial cells (HRECs) in a dose-dependent manner without inducing apoptotic nuclear changes [1]. SH-11037 (30-600 nM) inhibits the migration of human retinal microvascular endothelial cells (HRECs) in a dose-dependent manner, with significant inhibitory effects observed at concentrations ≥300 nM [1]. SH-11037 (30-500 nM) dose-dependently inhibited the formation of tubular structures in human retinal microvascular endothelial cells (HRECs) on Matrigel, with significant inhibitory effects at concentrations ≥100 nM [1]. SH-11037 (50-600 nM) induced minimal apoptosis in human retinal microvascular endothelial cells (HRECs), with apoptotic cell ratio <10% at concentrations up to 600 nM [1]. SH-11037 (30-1000 nM) did not reduce the viability of human retinal microvascular endothelial cells (HRECs) [1]. SH-11037 (100-1000 nM; 48 hours) caused dose-dependent G2/M phase cell cycle arrest in human retinal microvascular endothelial cells (HRECs) without significantly inducing apoptosis [1]. SH-11037 (1 μM; maximum 2 hours) is stable in phosphate buffer at pH 7.4, but is rapidly and quantitatively enzymatically hydrolyzed to SH-11008 in mouse plasma (half-life 0.018 min), while hydrolysis is slower in dog (half-life 69.1 min) and human plasma (half-life 73.2 min) [2]. SH-11037 (1 μM; maximum 2 hours) is rapidly hydrolyzed to SH-11008 mainly by carboxylesterase in mouse plasma and mouse eye homogenate; in dog plasma, hydrolysis is slower mediated by paraoxonase 1 and butyrylcholinesterase, while in human plasma, only paraoxonase 1 is mediated [2].
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|---|---|
| ln Vivo |
In male ICR mice, after intravenous injection of SH-11037 (5-10 mg/kg; intravenous injection, oral administration; single dose), SH-11037 was rapidly and almost completely converted to its metabolite SH-11008 (metabolism rate = 102.7%), and after oral administration, neither SH-11037 nor SH-11008 was detectable in plasma [2]. SH-11037 (1-10 μM) inhibited ocular angiogenesis in zebrafish larvae [4]. SH-11037 (0.1-100 μM; intravenous injection; single dose) had no ocular toxicity [4]. SH-11037 (0.1-10 μM; intravenous injection; single dose) inhibited choroidal neovascularization (CNV) lesion volume in a dose-dependent manner [4].
|
| Cell Assay |
Cell viability assay [1]
Cell Types: Human retinal microvascular endothelial cells Tested Concentrations: 100 nM; 300 nM; 1000 nM Incubation Duration: 48 hours Experimental Results: The cell cycle of HREC cells was arrested at the G2/M phase. |
| Animal Protocol |
Animal/Disease Models:ICR (male, 8 weeks old, 30-35 g) [2]
Doses: 5 mg/kg Route of Administration: Intravenous injection; single dose Experimental Results: Plasma concentrations remained below the limit of quantitation (<0.24 ng/mL) throughout the 24-hour timeframe. The peak concentration (Cmax) of the hydrolysate was 738.1 ng/mL (5 min), the area under the curve (AUCinf) was 14,728.5 ng·min/mL, and the half-life (t1/2) was 3.6 min. Concentrations above the limit of quantitation were detected within 30 minutes. The metabolite conversion rate reached 102.7%. Animal/Disease Models:ICR (male, 8 weeks old, 30-35 g) [2] Doses: 10 mg/kg Route of Administration: Oral; single dose Experimental Results: Plasma concentrations were below the limit of quantitation over a 24-hour period. Animal/Disease Models:C57BL/6J (female, 6-8 weeks old) [4] Doses: 0.1 μM; 1 μM; 10 μM; 100 μM Route of Administration: Intravenous injection; single dose Experimental Results: No histological changes were observed in retinal sections. No morphological changes were observed in retinal thickness. No signs of retinal damage, apoptosis, or inflammation were observed. Animal/Disease Models:C57BL/6J (female, 6-8 weeks old) [4] Doses: 0.1 μM; 0.3 μM; 1 μM; 10 μM Route of Administration: Intravenous injection; single dose Experimental Results: Compared with the solvent control group, the CNV lesion area was reduced at 1 μM and 10 μM concentrations. Compared with the solvent treatment group, the CNV lesion permeability was reduced. |
| References |
|
| Molecular Formula |
C34H39NO10
|
|---|---|
| Molecular Weight |
621.67
|
| CAS # |
1638153-78-2
|
| Appearance |
Typically exists as solids at room temperature
|
| SMILES |
COC1=C2C(OCC(C2=O)CC3=CC(OC([C@@H](NC(OC(C)(C)C)=O)CC4=CC=CC=C4)=O)=C(C=C3)OC)=CC(OC)=C1OC
|
| 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)
|
| 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 | 1.6086 mL | 8.0429 mL | 16.0857 mL | |
| 5 mM | 0.3217 mL | 1.6086 mL | 3.2171 mL | |
| 10 mM | 0.1609 mL | 0.8043 mL | 1.6086 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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