Dihydroergocristine mesylate

Names

[ Name ]:
Dihydroergocristine mesylate

[Synonym ]:
dihydroergocristine methanesulphonate
DIHYDROERGOCRYSTINE METHANESULFONATE SALT
dihydroergocristine methane sulfonate
DIHYDROERGOCRISTINE METHANESULFONATE ERG OT ALKALOID,VASOC
Dihydroergocristine mesilate
9,10-DihydroergocristineMethanesulfonate
EINECS 246-434-6
dihydroergocristine methanesulfonate salt
Dihydroergocristine mesylate,(5'α,10α)-9,10-Dihydro-12'-hydroxy-2'-(1-methylethyl)-5'-(phenylmethyl)-ergotaman-3',6',18-trionemesylate
PACAP 1-38
MFCD00153792
dihydroergocristinmesilat
DIHYDROERGOCRISTINE MESYLATE
dihydroergocristine

Biological Activity

[Description]:

Dihydroergocristine mesylate (DHEC mesylate) is a inhibitor of γ-secretase (GSI), reduces the production of the Alzheimer's disease amyloid-β peptides, binds directly to γ-secretase and Nicastrin with equilibrium dissociation constants (Kd) of 25.7 nM and 9.8 μM, respectively[1].

[Related Catalog]:

Research Areas >> Neurological Disease

[In Vitro]

Dihydroergocristine (DHEC) (2-20 μM; 24 hours) has an IC50 value of 25 μM for inhibiting the activity of γ-secretase in T100 cells without affecting cell viability[1]. Dihydroergocristine (2-20 μM; 24 hours) inhibits cellular Aβ production and causes a dose-dependent accumulation of carboxy-terminal fragments of APP (APP-CTFs) in HEK293 and decreases γ-secretase activity in fibroblast cells[1]. Western Blot Analysis[1] Cell Line: WT HEK293 cells; Fibroblast cells Concentration: 2 μM, 5 μM, 10 μM, 20 μM Incubation Time: 24 hours Result: Increased APP-CTFs accumulation in a dose-dependent manner.

[References]

[1]. Lei X, et al. The FDA-approved natural product dihydroergocristine reduces the production of the Alzheimer's disease amyloid-β peptides. Sci Rep. 2015 Nov 16;5:16541.

Chemical & Physical Properties

[ Boiling Point ]:
899.3ºC at 760 mmHg

[ Molecular Formula ]:
C₃₆H₄₅N₅O₈S

[ Molecular Weight ]:
707.83600

[ Flash Point ]:
497.7ºC

[ Exact Mass ]:
707.29900

[ PSA ]:
180.96000

[ LogP ]:
3.50660

[ Vapour Pressure ]:
8.49E-35mmHg at 25°C

[ Storage condition ]:
Store at RT

[ Water Solubility ]:
H2O: 10 mg/mL

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: KE7600000

CHEMICAL NAME :: Ergotamane-3',6',18-trione, 9,10-dihydro-12'-hydroxy-2'-(1-methylethyl)-5'-(pheny lmethyl)-, (5'-alpha,10-alpha)-, monomethanesulfonate (salt)

CAS REGISTRY NUMBER :: 24730-10-7

LAST UPDATED :: 199703

DATA ITEMS CITED :: 8

MOLECULAR FORMULA :: C35-H41-N5-O5.C-H4-O3-S

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 2643 mg/kg

TOXIC EFFECTS :: Behavioral - general anesthetic Behavioral - tremor Behavioral - convulsions or effect on seizure threshold

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 42,1381,1992

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 585 mg/kg

TOXIC EFFECTS :: Behavioral - general anesthetic Behavioral - tremor Behavioral - convulsions or effect on seizure threshold

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 42,1381,1992

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 91 mg/kg

TOXIC EFFECTS :: Behavioral - general anesthetic Behavioral - tremor Behavioral - convulsions or effect on seizure threshold

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 42,1381,1992

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >2500 mg/kg

TOXIC EFFECTS :: Behavioral - general anesthetic Behavioral - tremor Behavioral - convulsions or effect on seizure threshold

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 42,1381,1992

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 120 mg/kg

TOXIC EFFECTS :: Behavioral - general anesthetic Behavioral - tremor Behavioral - convulsions or effect on seizure threshold

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 42,1381,1992

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 70 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: USXXAM United States Patent Document. (U.S. Patent Office, Box 9, Washington, DC 20231) Volume(issue)/page/year: #4176182

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: >1250 mg/kg

TOXIC EFFECTS :: Behavioral - tremor Behavioral - excitement Gastrointestinal - nausea or vomiting

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 42,1381,1992

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: >50 mg/kg

TOXIC EFFECTS :: Behavioral - tremor Behavioral - excitement Gastrointestinal - nausea or vomiting

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 42,1381,1992

Safety Information

[ RIDADR ]:
UN 1544 6

[ WGK Germany ]:
2

[ RTECS ]:
KE7600000

[ Packaging Group ]:
III

[ Hazard Class ]:
6.1(b)

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