| Size | Price | Stock | Qty |
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| 25mg |
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| 50mg |
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Purity: ≥98%
Genz-123346 is a novel, potent and selective glucosylceramide synthase inhibitor with potential anticancer activity. The cytotoxic anti-cancer agents' ability to kill tumor cells can be increased when cells are exposed to non-toxic concentrations of Genz-123346 and other GCS inhibitors. P-gp (ABCB1, gP-170) and other multi-drug resistance efflux pumps are substrates of Genz-123346 and a few other GCS inhibitors. The primary cause of the chemosensitization caused by Genz-123346 in cell lines that were chosen to overexpress P-gp or that express P-gp endogenously was its impact on P-gp function.
| Targets |
GM1 ( IC50 = 14 nM )
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|---|---|
| ln Vitro |
Cells exposed to nontoxic concentrations of Genz-123346 and other GCS inhibitors can increase the ability of cytotoxic anti-cancer agents to kill tumor cells. Genz-123346 and a few other GCS inhibitors serve as substrates for efflux pumps that are resistant to multiple drugs, like P-gp (ABCB1, gP-170). The primary cause of Genz-123346's chemosensitization in cell lines chosen to overexpress P-gp or that express P-gp endogenously is its effects on P-gp function[2]. Genz-123346(Genz) is an autophagy flux enhancer[3].
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| ln Vivo |
Genz-123346 decreased glucose and A1C levels and enhanced glucose tolerance in the Zucker diabetic fatty rat. Additionally, drug therapy maintained the animals' capacity to secrete insulin and stopped the loss of pancreatic beta-cell function. Treatment with Genz-123346 normalized A1C levels and enhanced glucose tolerance in the diet-induced obese mouse. The medication has been demonstrated to have an oral bioavailability of 10% in mice and 30% in rats, with a half-life in plasma of 30 to 60 minutes[1]. Genz-123346 treatment reduces renal GlcCer and GM3 levels in a dose-dependent manner, effectively inhibiting cystic disease. A direct effect of Genz-123346 on the Akt-mTOR signaling pathway is observed, with reduced phosphorylation of Akt and ribosomal protein S6[4].
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| Animal Protocol |
Rats: In water, Genz-123346 dissolves. After receiving Genz-123346 (75 mg/kg) for six weeks, Zucker diabetic fatty rats are fasted for the entire night. The fasted rats are put under anesthesia and given five human insulin shots into their hepatic portal veins the next morning. Two minutes after injection, the liver and quadriceps muscle are removed and instantly frozen in liquid nitrogen. The immunoprecipitated insulin receptor By using immunoblotting, the immunoprecipitates are examined[1].
Mice: For eight weeks, C57BL/6 mice are given a high-fat (45% of kcal) diet. Obese mice with similar body weight gain, insulin, and glucose levels are placed in the treated or control groups. After that, the mice are given water or Genz-123346 every day for ten weeks[1]. |
| References |
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| Molecular Formula |
C24H38N2O4
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|---|---|
| Molecular Weight |
418.5695
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| Exact Mass |
418.28
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| Elemental Analysis |
C, 68.87; H, 9.15; N, 6.69; O, 15.29
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| CAS # |
491833-30-8
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| Related CAS # |
Genz-123346; 943344-58-9
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| Appearance |
White to off-white solid powder
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| SMILES |
CCCCCCCCC(=O)N[C@H](CN1CCCC1)[C@@H](C2=CC3=C(C=C2)OCCO3)O
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| InChi Key |
JMNXWOFCUJJYEO-HYBUGGRVSA-N
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| InChi Code |
InChI=1S/C24H38N2O4/c1-2-3-4-5-6-7-10-23(27)25-20(18-26-13-8-9-14-26)24(28)19-11-12-21-22(17-19)30-16-15-29-21/h11-12,17,20,24,28H,2-10,13-16,18H2,1H3,(H,25,27)/t20-,24-/m1/s1
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| Chemical Name |
N-[(1R,2R)-1-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-hydroxy-3-pyrrolidin-1-ylpropan-2-yl]nonanamide
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| Synonyms |
Genz123346; Genz-123346; Genz 123346
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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: ~84 mg/mL (~200.7 mM)
Ethanol: ~84 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 3 mg/mL (7.17 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 30.0 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: ≥ 3 mg/mL (7.17 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 30.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: ≥ 3 mg/mL (7.17 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3891 mL | 11.9454 mL | 23.8909 mL | |
| 5 mM | 0.4778 mL | 2.3891 mL | 4.7782 mL | |
| 10 mM | 0.2389 mL | 1.1945 mL | 2.3891 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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