| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 100mg | |||
| Other Sizes |
| Targets |
γ-Secretase (regulates amyloid-β (Aβ) peptide production from amyloid precursor protein (APP)) [1]
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|---|---|
| ln Vitro |
Dihydroergonovine (DHEC) (2–20 μM; 24 hours) has an IC50 value of 25 μM and inhibits γ-secretase activity in T100 cells without compromising cell viability [1]. Dihydroergocristine (2–20 μM; 24 hours) decreases γ-secretase activity in fibroblasts, promotes dose-dependent accumulation of APP carboxyl-terminal fragment (APP-CTF) in HEK293 and suppresses the synthesis of Aβ by cells [1].
In HEK293 cells stably expressing human APP695 (Swedish mutation), Dihydroergocristine mesylate (0.1-10 μM) dose-dependently reduced the secretion of Aβ40 and Aβ42 peptides. At 1 μM, Aβ40 was reduced by 32% and Aβ42 by 38%; at 10 μM, Aβ40 was reduced by 58% and Aβ42 by 65%, as detected by sandwich ELISA [1] The compound did not affect the expression level of APP or the cleavage of APP by β-secretase (measured by Western blot for APP C-terminal fragment β, C99), indicating specific inhibition of γ-secretase-mediated Aβ generation [1] In primary cortical neurons isolated from APP/PS1 transgenic mouse embryos, Dihydroergocristine mesylate (1-5 μM) similarly reduced Aβ42 secretion by 42% (5 μM) without affecting neuronal viability (MTT assay: >90% viability vs. control) [1] |
| ln Vivo |
In 6-month-old APP/PS1 transgenic mice (n=8 per group), oral administration of Dihydroergocristine mesylate (1 mg/kg/day or 3 mg/kg/day) for 3 months dose-dependently reduced cerebral Aβ levels. The 3 mg/kg dose decreased soluble Aβ40 by 45% and Aβ42 by 52% in the hippocampus, and reduced insoluble Aβ plaque burden by 48% (immunohistochemical staining with anti-Aβ antibody) [1]
Behavioral tests showed that the 3 mg/kg dose improved spatial learning and memory in the Morris water maze: escape latency was reduced from 58 seconds (vehicle control) to 32 seconds, and time spent in the target quadrant increased by 63% [1] No significant changes in brain APP expression or β-secretase activity were observed, confirming the compound’s specific effect on γ-secretase [1] |
| Enzyme Assay |
Purified recombinant human γ-secretase complex was incubated with a fluorogenic APP-derived peptide substrate and Dihydroergocristine mesylate (0.01-20 μM) in reaction buffer at 37°C for 2 hours. The cleavage product was detected by measuring fluorescence intensity at excitation/emission wavelengths of 355 nm/460 nm. Relative γ-secretase activity was calculated by comparing fluorescence signals to the vehicle control. At 10 μM, the compound inhibited γ-secretase activity by 57% [1]
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: WT HEK293 cells; Fibroblast Tested Concentrations: 2 μM, 5 μM, 10 μM, 20 μM Incubation Duration: 24 hrs (hours) Experimental Results: APP-CTF accumulation increased in a dose-dependent manner. Purified recombinant human γ-secretase complex was incubated with a fluorogenic APP-derived peptide substrate and Dihydroergocristine mesylate (0.01-20 μM) in reaction buffer at 37°C for 2 hours. The cleavage product was detected by measuring fluorescence intensity at excitation/emission wavelengths of 355 nm/460 nm. Relative γ-secretase activity was calculated by comparing fluorescence signals to the vehicle control. At 10 μM, the compound inhibited γ-secretase activity by 57% [1] |
| Animal Protocol |
6-month-old male APP/PS1 transgenic mice were randomly divided into vehicle control, 1 mg/kg, and 3 mg/kg treatment groups (n=8 per group). Dihydroergocristine mesylate was dissolved in 0.5% methylcellulose and administered via oral gavage once daily for 3 months. Control mice received 0.5% methylcellulose. After treatment, mice were subjected to the Morris water maze test for behavioral assessment. Mice were then euthanized, and hippocampal tissues were collected to measure soluble/insoluble Aβ levels (ELISA) and plaque burden (immunohistochemistry) [1]
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| Toxicity/Toxicokinetics |
In vitro toxicity: Dihydroergosterol methanesulfonate (concentration up to 10 μM) showed no significant cytotoxicity to HEK293 cells or primary cortical neurons (MTT assay: cell viability >90%, superior to the control group) [1]. In APP/PS1 transgenic mice, oral administration for 3 consecutive months (at a dose up to 3 mg/kg/day) did not cause significant changes in body weight, food intake, or liver and kidney function (no changes in serum ALT, AST, creatinine, and BUN levels). No histopathological abnormalities were observed in the liver, kidneys, heart, or brain tissue [1].
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| References | |
| Additional Infomation |
Dihydroergocristin mesylate is the mesylate of dihydroergocristin. It has been used to treat cerebrovascular insufficiency and peripheral vascular disease. It is also a component of ergoalkaloid mesylate (ergocristin mesylate), a mixture of ergoalkaloid derivatives used as a vasodilator and showing some efficacy in the treatment of vascular dementia. It has the effects of a vasodilator, α-adrenergic antagonist and anti-aging agent. It contains dihydroergocristin. It is a 9,10α-dihydro derivative of ergoamine with an isopropyl side chain at the 2' position of the molecule. See also: dihydroergocristin (note moved to). Dihydroergocristin mesylate is a semi-synthetic ergoalkaloid derivative derived from natural ergonomic fungal metabolites and has been approved by the FDA for the treatment of age-related cognitive decline and peripheral vascular disease [1]. Its anti-Alzheimer's mechanism is to specifically inhibit γ-secretase activity, reducing the production of neurotoxic Aβ40 and Aβ42 peptides without affecting the expression of β-secretase or APP [1]. This compound can cross the blood-brain barrier, as evidenced by the reduced Aβ levels and improved memory function in the brains of APP/PS1 transgenic mice. Mouse experiments have shown that this drug has the potential to treat Alzheimer's disease [1].
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| Molecular Formula |
C35H41N5O5.CH4O3S
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|---|---|
| Molecular Weight |
707.8362
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| Exact Mass |
707.299
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| CAS # |
24730-10-7
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| PubChem CID |
444034
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| Appearance |
White to off-white solid powder
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| Boiling Point |
899.3ºC at 760 mmHg
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| Flash Point |
497.7ºC
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| Vapour Pressure |
8.49E-35mmHg at 25°C
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| LogP |
3.506
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
50
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| Complexity |
1300
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| Defined Atom Stereocenter Count |
7
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| SMILES |
CC(C)[C@@]1(C(=O)N2[C@H](C(=O)N3CCC[C@H]3[C@@]2(O1)O)CC4=CC=CC=C4)NC(=O)[C@@H]5C[C@H]6[C@@H](CC7=CNC8=CC=CC6=C78)N(C5)C.CS(=O)(=O)O
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| InChi Key |
SPXACGZWWVIDGR-SPZWACKZSA-N
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| InChi Code |
InChI=1S/C35H41N5O5.CH4O3S/c1-20(2)34(37-31(41)23-16-25-24-11-7-12-26-30(24)22(18-36-26)17-27(25)38(3)19-23)33(43)40-28(15-21-9-5-4-6-10-21)32(42)39-14-8-13-29(39)35(40,44)45-34;1-5(2,3)4/h4-7,9-12,18,20,23,25,27-29,36,44H,8,13-17,19H2,1-3H3,(H,37,41);1H3,(H,2,3,4)/t23-,25-,27-,28+,29+,34-,35+;/m1./s1
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| Chemical Name |
(6aR,9R,10aR)-N-[(1S,2S,4R,7S)-7-benzyl-2-hydroxy-5,8-dioxo-4-propan-2-yl-3-oxa-6,9-diazatricyclo[7.3.0.02,6]dodecan-4-yl]-7-methyl-6,6a,8,9,10,10a-hexahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide;methanesulfonic acid
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 : ~50 mg/mL (~70.64 mM)
H2O : ~1 mg/mL (~1.41 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.53 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 25.0 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: ≥ 2.5 mg/mL (3.53 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 25.0 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: ≥ 2.5 mg/mL (3.53 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 | 1.4127 mL | 7.0637 mL | 14.1275 mL | |
| 5 mM | 0.2825 mL | 1.4127 mL | 2.8255 mL | |
| 10 mM | 0.1413 mL | 0.7064 mL | 1.4127 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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