Mepazine hydrochloride

Mepazine hydrochloride (Pecazine hydrochloride) is a potent and selective MALT1 protease inhibitor with IC50s of 0.83 and 0.42 μM for GSTMALT1 full length and GSTMALT1 325-760, respectively. Mepazine hydrochloride affects viability of ABC-DLBCL cells by enhancing apoptosis[1].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> NF-κB >> MALT1

MALT1[1]

Mepazine (5-20 μM; 4 days) causes a decrease of cell viability in the activated B cell subtype of diffuse large B cell lymphoma (ABCDLBCL) cells, without significantly affecting GCB-DLBCL cells[1]. Cell Viability Assay[1] Cell Line: ABC-DLBCL cell lines (HBL1, OCI-Ly3, U2932, TMD8, OCI-Ly10) and GCB-DLBCL cell lines (BJAB, Su-DHL-6, Su-DHL-4) Concentration: 5, 10, and 20 μM Incubation Time: 4 days Result: Caused a decrease of cell viability in the ABC-DLBCL cells HBL1, OCI-Ly3, U2932, and TMD8, without significantly affecting GCB-DLBCL cells.

Mepazine (16 mg/kg; intraperitoneal administration) interferes with growth and induces apoptosis of ABC-DLBCL cell line OCI-Ly10 in NOD/scid IL-2Rgnull (NSG) mice with a murine DLBCL xenogeneic tumor model. Daily administration of Mepazine strongly impairs the expansion of the ABC-DLBCL cell line OCI-Ly10[1]. Animal Model: 6- to 8-week-old female NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice with a murine DLBCL xenogeneic tumor model[1] Dosage: 400 μg per animal (25 g), corresponding to approximately 16 mg/kg Administration: Intraperitoneal administration; started 1 or 12 days after transplantation and given continuously every 24 hr; daily application Result: Daily administration strongly impaired the expansion of the ABC-DLBCL cell line OCI-Ly10.

[1]. Nagel D, et al. Pharmacologic inhibition of MALT1 protease by phenothiazines as a therapeutic approach for the treatment of aggressive ABC-DLBCL. Cancer Cell. 2012 Dec 11;22(6):825-37.

MOLECULAR FORMULA :

C19-H22-N2-S.Cl-H

MOLECULAR WEIGHT :

346.95

WISWESSER LINE NOTATION :

T C666 BN ISJ B1- CT6NTJ A1 &GH

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 :

1 gm/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

27ZQAG "Psychotropic Drugs and Related Compounds," 2nd ed., Usdin, E., and D.H. Efron, Washington, DC, 1972 Volume(issue)/page/year: -,28,1972

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

20 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

27ZQAG "Psychotropic Drugs and Related Compounds," 2nd ed., Usdin, E., and D.H. Efron, Washington, DC, 1972 Volume(issue)/page/year: -,28,1972

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

155 mg/kg

TOXIC EFFECTS :

Nutritional and Gross Metabolic - body temperature decrease

REFERENCE :

CKFRAY Ceskoslovenska Farmacie. (PNS-Ustredni Expedice a Dovoz Tisku, Kafkova 19, 160 00 Prague 6, Czechoslovakia) V.1- 1952- Volume(issue)/page/year: 6,365,1957

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

200 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

27ZQAG "Psychotropic Drugs and Related Compounds," 2nd ed., Usdin, E., and D.H. Efron, Washington, DC, 1972 Volume(issue)/page/year: -,28,1972

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

750 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

27ZQAG "Psychotropic Drugs and Related Compounds," 2nd ed., Usdin, E., and D.H. Efron, Washington, DC, 1972 Volume(issue)/page/year: -,28,1972

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

62 mg/kg

TOXIC EFFECTS :

Behavioral - sleep

REFERENCE :

APTOA6 Acta Pharmacologica et Toxicologica. (Copenhagen, Denmark) V.1-59, 1945-86. For publisher information, see PHTOEH Volume(issue)/page/year: 19,87,1962

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

1 gm/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

27ZQAG "Psychotropic Drugs and Related Compounds," 2nd ed., Usdin, E., and D.H. Efron, Washington, DC, 1972 Volume(issue)/page/year: -,28,1972

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

20 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

27ZQAG "Psychotropic Drugs and Related Compounds," 2nd ed., Usdin, E., and D.H. Efron, Washington, DC, 1972 Volume(issue)/page/year: -,28,1972