Clofilium tosylate

Names

[ Name ]:
Clofilium tosylate

[Synonym ]:
N-[4-(4-Chlorophenyl)butyl]-N,N-diethyl-1-heptanaminium 4-methylbenzenesulfonate
Benzenebutanaminium,4-chloro-N,N-diethyl-N-heptyl-,salt with 4-methylbenzenesulfonicacid (1:1)
4-Chloro-N,N-diethyl-N-heptylbenzenebutanaminium tosylate
Clofilium tosylate
Prestwick_682

Biological Activity

[Description]:

Clofilium tosylate, a potassium channel blocker, induces apoptosis of human promyelocytic leukemia (HL-60) cells via Bcl-2-insensitive activation of caspase-3. Antiarrhythmic agent[1].

[Related Catalog]:

Research Areas >> Cancer

Research Areas >> Cardiovascular Disease

Signaling Pathways >> Membrane Transporter/Ion Channel >> Potassium Channel

[Target]

Potassium channel[1]

[In Vitro]

HL-60 cells treated with Clofilium (0-20 μM; 24, 48, and 72 hours) lead to suppression of viability and proliferation in both time and concentration-dependent manners. Cell viability decreases significantly in HL-60 cells treated with 2.5 μM to 10 μM of Clofilium[1]. Clofilium (10 μM, 12 hours) induces the proteolytic cleavage of inactive procaspase-3, p34 into its active form, p17 and subsequent cleavage of its substrate PARP at 2 h after exposure to 10 mM Clofilium. However, there is no significant change in expression of Bcl-2 and Bax proteins[1]. Cell Viability Assay[1] Cell Line: HL-60 cells Concentration: 0-20 μM Incubation Time: 24, 48, and 72 hours Result: Inhibited HL-60 cells with IC50s of 6.3 μM for 24 hours, 3.4 μM for 48 hours, 2.4 μM for 72 hours, respectively. Western Blot Analysis[1] Cell Line: HL-60 cells Concentration: 10 μM Incubation Time: 12 hours Result: Induced proteolytic cleavage of caspase-3 and subsequent cleavage of its substrate, PARP, while Bcl-2 and Bax proteins were unaltered.

[References]

[1]. Choi BY, et al. Clofilium, a potassium channel blocker, induces apoptosis of human promyelocytic leukemia (HL-60) cells via Bcl-2-insensitive activation of caspase-3. Cancer Lett. 1999 Dec 1;147(1-2):85-93.

Chemical & Physical Properties

[ Molecular Formula ]:
C₂₈H₄₄ClNO₃S

[ Molecular Weight ]:
510.172

[ Exact Mass ]:
509.273041

[ PSA ]:
65.58000

[ LogP ]:
8.46960

[ Storage condition ]:
2-8℃

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: CY9040870

CAS REGISTRY NUMBER :: 92953-10-1

LAST UPDATED :: 198910

DATA ITEMS CITED :: 2

MOLECULAR FORMULA :: C21-H37-Cl-N.C7-H7-O3-S

MOLECULAR WEIGHT :: 510.24

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 :: 456 mg/kg

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

REFERENCE :: NDADD8 New Drugs Annual: Cardiovascular Drugs. (New York, NY) V.1-2, 1983-84. For publisher information, see NCDREP. Volume(issue)/page/year: 2,103,1984

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 416 mg/kg

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

REFERENCE :: NDADD8 New Drugs Annual: Cardiovascular Drugs. (New York, NY) V.1-2, 1983-84. For publisher information, see NCDREP. Volume(issue)/page/year: 2,103,1984

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H302

[ Personal Protective Equipment ]:
dust mask type N95 (US);Eyeshields;Faceshields;Gloves

[ Hazard Codes ]:
Xn: Harmful;

[ Risk Phrases ]:
22

[ Safety Phrases ]:
36

[ RIDADR ]:
NONH for all modes of transport

[ RTECS ]:
CY9040870

Articles

Block of heart potassium channels by clofilium and its tertiary analogs: relationship between drug structure and type of channel blocked.

Mol. Pharmacol. 34 , 60-66, (1988)

The whole-cell arrangement of the patch clamp was used to study delayed rectifier and inward rectifier K channels in isolated guinea pig ventricular cells. Block of these channels by an externally app...

The differential response of normal and ischaemic Purkinje fibres to clofilium, d-sotalol and bretylium.

Cardiovasc. Res. 23 , 554-559, (1989)

To determine whether ischaemic tissue is more sensitive than normal tissue to class III anti-arrhythmic agents, we studied the effects of the class III agents clofilium, d-sotalol and bretylium on nor...

Clofilium and other class III agents. Steinberg, et al., Williams, et al.

Handbook of Experimental Pharmacology Berlin Heidelberg 89 , 389, (1989)