Parbendazole

Parbendazole is a potent inhibitor of microtubule assembly, destabilizes tubulin, with an EC50 of 8.79 nM, and exhibits a broad-spectrum anthelmintic activity.

Signaling Pathways >> Cell Cycle/DNA Damage >> Microtubule/Tubulin

Signaling Pathways >> Cytoskeleton >> Microtubule/Tubulin

Research Areas >> Infection

EC50: 8.79 nM (tubulin)[1]

Parbendazole is a tubulin destabilizer, with an EC50 of 8.79 nM, and can induce DNA damage[1]. Parbendazole (2-10 μM) inhibits the assembly of microtubules dose-dependently, with an IC50 of 3 μM. Parbendazole (2-20 μM)-treated cells show an complete absence of microtubules in Vero cells[2]. Parbendazole (up to 10 μM) inhibits the growth of CLd-AXE myxamoebae. Parbendazole (2-5 μM) potently inhibits tubulin purified from the wild-type myxamoebae[3].

Pure tubulin is obtained from sheep brain by 2 cycles of assembly and disassembly in vitro. Immediately prior to use the protein is centrifuged at 130000 g for 30 min to remove any aggregates. It is used at a protein concentration of 0-2 mg/mL in 0.025 M Pipes buffer, 0-5 mM EGTA, 0-25 mM Mg2SOsup>4, 0.1 mM GTP. Drug binding is determined by equilibrium dialysis using concentrations of parbendazole between 0.1 μM and 4 μM, and 2% (v/v) DMF (dimethyl formamide) as a carrier. Equilibrium is achieved by constant stirring for 2 h at 26°C, bovine serum albumin being used as a standard. 200 μL aliquots are counted in PCS in a 25-200B liquid scintillation counter[2].

Vero cells, an established cell line derived from monkey kidney are seeded in DMEM supplemented with 10% (v/v) foetal calf serum onto glass coverslips in multiwell dishes. They are allowed to settle, and spread for 2-5 h in a humid atmosphere at 37°C. After this time the medium is changed to DMEM containing 2, 10 or 20 μM parbendazole and 1% (v/v) DMSO controls contained 1 % (v/v) DMSO or had no additions[2].

[1]. Lo YC, et al. Computational Cell Cycle Profiling of Cancer Cells for Prioritizing FDA-Approved Drugs with Repurposing Potential. Sci Rep. 2017 Sep 12;7(1):11261.

[2]. Lo YC, et al. Computational Cell Cycle Profiling of Cancer Cells for Prioritizing FDA-Approved Drugs with Repurposing Potential. Sci Rep. 2017 Sep 12;7(1):11261.

[3]. Havercroft JC, et al. Binding of parbendazole to tubulin and its influence on microtubules in tissue-culture cells as revealed by immunofluorescence microscopy. J Cell Sci. 1981 Jun;49:195-204.

[4]. Havercroft JC, et al. Binding of parbendazole to tubulin and its influence on microtubules in tissue-culture cells as revealed by immunofluorescence microscopy. J Cell Sci. 1981 Jun;49:195-204.

[5]. Foster KE, et al. A mutant beta-tubulin confers resistance to the action of benzimidazole-carbamate microtubule inhibitors both in vivo and in vitro. Eur J Biochem. 1987 Mar 16;163(3):449-55.

[6]. Foster KE, et al. A mutant beta-tubulin confers resistance to the action of benzimidazole-carbamate microtubule inhibitors both in vivo and in vitro. Eur J Biochem. 1987 Mar 16;163(3):449-55.

Nocodazole | Monomethyl auristatin E | VcMMAE | Mertansine | Eribulin mesylate | Epothilone D | Vinorelbine (ditartrate) | epothilone B | McMMAF | MMAF (Hydrochloride) | Ixabepilone | Taltobulin | Estramustine phosphate sodium | Ansamitocin P-3 | Combretastatin A4 disodium phosphate

MOLECULAR FORMULA :

C13-H17-N3-O2

MOLECULAR WEIGHT :

247.33

WISWESSER LINE NOTATION :

T56 BM DNJ CMVO1 G4

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 :

>40 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

1700 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Bird - chicken

DOSE/DURATION :

>40 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - domestic

DOSE/DURATION :

660 mg/kg

TOXIC EFFECTS :

Gastrointestinal - ulceration or bleeding from stomach

TYPE OF TEST :

LD - Lethal dose

ROUTE OF EXPOSURE :

Unreported

SPECIES OBSERVED :

Mammal - cattle

DOSE/DURATION :

>1200 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Unreported

SPECIES OBSERVED :

Mammal - cattle

DOSE/DURATION :

450 mg/kg/6D-I

TOXIC EFFECTS :

Gastrointestinal - other changes

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

1200 mg/kg

SEX/DURATION :

female 7-18 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - gastrointestinal system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

80 mg/kg

SEX/DURATION :

female 8-15 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetal death Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

80 mg/kg

SEX/DURATION :

female 8-15 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

150 mg/kg

SEX/DURATION :

female 8-15 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - other developmental abnormalities

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

80 mg/kg

SEX/DURATION :

female 8-15 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

4 gm/kg

SEX/DURATION :

female 6-15 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - respiratory system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

90 mg/kg

SEX/DURATION :

female 13 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

400 mg/kg

SEX/DURATION :

female 6-15 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Specific Developmental Abnormalities - other developmental abnormalities

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

10 gm/kg

SEX/DURATION :

female 6-15 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

16 gm/kg

SEX/DURATION :

female 6-15 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Specific Developmental Abnormalities - urogenital system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

130 mg/kg

SEX/DURATION :

female 6-18 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - abortion Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

780 mg/kg

SEX/DURATION :

female 6-18 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

60 mg/kg

SEX/DURATION :

female 21 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Effects on Newborn - physical

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

30 mg/kg

SEX/DURATION :

female 12 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - other measures of fertility

MUTATION DATA

TYPE OF TEST :

Mutation test systems - not otherwise specified

TEST SYSTEM :

Mammal - domestic Leukocyte

DOSE/DURATION :

1 mg/L

REFERENCE :

THERAP Therapie. (Doin, Editeurs, 8, Place de l'Odeon, F-75006 Paris, France) V.1- 1946- Volume(issue)/page/year: 31,505,1976