hydrocotarnine
Names
[ CAS No. ]:
550-10-7
[ Name ]:
hydrocotarnine
[Synonym ]:
8-methoxy-2-methyl-6,7-methylenedioxy-1,2,3,4-tetrahydroisoquinoline
Hydrocotarnine
Biological Activity
[Description]:
Hydrocotarnine is a Cbl inhibitor, and results in inflammasome-mediated IL-18 secretion in colitis. Hydrocotarnine increases expression of GLUT1 and cellular glucose uptake in glycolytic metabolism. Hydrocotarnine acts as an agent that provides analgesic effect in cancer research[1][2][3].
[Related Catalog]:
[Target]
Cbl[1][2]
[In Vitro]
Hydrocotarnine is an analgesic agent (CRIN-2), with the patent ID of WO2011160016A2[1]. Hydrocotarnine (10 μM; 1 h) elevates the secretion of IL-1β and IL-18, and (0.1-10 μM; 1 h) increases the global level of tyrosine-phosphorylated proteins in THP-1 cells[1]. Hydrocotarnine (50 μM; 0-100 min) increases the glycolytic capacity and glycolytic reserve capacity in THP-1-derived macrophages[2]. Hydrocotarnine (50 μM; 16 h) inhibits Cbl and increases the total GLUT1 protein in THP-1-derived macrophages[2]. Hydrocotarnine is known to enhance the analgesic effect of opioids, and alleviates cancer pain[3]. Western Blot Analysis[1] Cell Line: THP-1 cells Concentration: 0.1, 1, 10 μM Incubation Time: 1 hour Result: Induced p-Pyk2 loss and increased the level of tyrosine-phosphorylated proteins in a dose-dependent manner.
[In Vivo]
Hydrocotarnine (10 mg/kg/d; i.p.; 9 d) shows inhibitory effect on Cbl and results in increasing IL-18 levels, indicating that NLRP3 inflammasome activation is enhanced in mice[1]. Hydrocotarnine (10 mg/kg/d; i.p.; 9 d) protects mice from DSS-induced colitis, with low scores of pathological evaluation of inflammation, epithelial defects, and crypt atrophy[1]. Animal Model: DSS-induced colitis model in C57BL/6 mice (6-9 weeks old)[1] Dosage: 10 mg/kg Administration: Intraperitoneal injection; once daily; 9 days while 2.5% DSS treatment began on day 1 and ended on day 7 Result: Significantly attenuated the weight loss of DSS-induced colitis mice compared to PBS-treated control mice, indicating that decreasing negative regulation of the NLRP3 inflammasome activation could attenuate colitis in an animal model.
[References]
Chemical & Physical Properties
[ Boiling Point ]:
342.4ºC at 760 mmHg
[ Molecular Formula ]:
C12H15NO3
[ Molecular Weight ]:
221.25200
[ Flash Point ]:
106.7ºC
[ Exact Mass ]:
221.10500
[ PSA ]:
30.93000
[ LogP ]:
1.34970
Toxicological Information
CHEMICAL IDENTIFICATION
- RTECS NUMBER :
- JI4825000
- CHEMICAL NAME :
- 1,3-Dioxolo(4,5-g)isoquinoline, 5,6,7,8-tetrahydro-4-methoxy-6-methyl-
- CAS REGISTRY NUMBER :
- 550-10-7
- BEILSTEIN REFERENCE NO. :
- 0017283
- LAST UPDATED :
- 199709
- DATA ITEMS CITED :
- 2
- MOLECULAR FORMULA :
- C12-H15-N-O3
- MOLECULAR WEIGHT :
- 221.28
HEALTH HAZARD DATA
ACUTE TOXICITY DATA
- TYPE OF TEST :
- LDLo - Lowest published lethal dose
- ROUTE OF EXPOSURE :
- Subcutaneous
- SPECIES OBSERVED :
- Rodent - mouse
- DOSE/DURATION :
- 160 mg/kg
- TOXIC EFFECTS :
- Behavioral - tremor Lungs, Thorax, or Respiration - dyspnea
- REFERENCE :
- PHARAT Pharmazie. (VEB Verlag Volk und Gesundheit, Neue Gruenstr. 18, Berlin DDR-1020, Ger. Dem. Rep.) V.1- 1946- Volume(issue)/page/year: 15,111,1960
- TYPE OF TEST :
- LDLo - Lowest published lethal dose
- ROUTE OF EXPOSURE :
- Intravenous
- SPECIES OBSERVED :
- Rodent - rabbit
- DOSE/DURATION :
- 100 mg/kg
- TOXIC EFFECTS :
- Behavioral - tremor Lungs, Thorax, or Respiration - dyspnea
- REFERENCE :
- PHARAT Pharmazie. (VEB Verlag Volk und Gesundheit, Neue Gruenstr. 18, Berlin DDR-1020, Ger. Dem. Rep.) V.1- 1946- Volume(issue)/page/year: 15,111,1960