Guanazole
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Guanazole is a ribonucleotide reductase (RNR) inhibitor that blocks replicative DNA synthesis by inhibiting deoxyribonucleotide biosynthesis. Guanazole selectively inhibits DNA synthesis in rapidly proliferating tissues, induces replication stress and G2/M phase arrest in Schizosaccharomyces pombe, and exhibits myelosuppressive, immunosuppressive, and anti-L1210 leukemia activities. Guanazole does not induce DNA repair and only shows slight mutagenicity towards Salmonella typhimurium TA102. Guanazole serves as an alternative tool to Hydroxyurea (HY-B0313) for replication checkpoint studies in Schizosaccharomyces pombe. Guanazole can be applied in research related to leukemia and solid tumors.
For research use only. We do not sell to patients.
- CAS No.: 1455-77-2
- Formula: C2H5N5
- Molecular Weight:99.09
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Storage:
4°C, protect from light
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Biological Activity
Description
In Vitro
Guanazole (2.52-252 μmole/plate) exhibits weak mutagenicity against Salmonella typhimurium strain TA102, with a mutagenic activity range of 0.60 to 1.63 mutants/μmole[1].
Guanazole (0.05-50.0 mM) does not induce DNA repair in primary rat hepatocyte cultures[1].
Guanazole (15 mM; 18 h) inhibits replicative DNA synthesis in primary rat hepatocyte cultures[1].
Guanazole (15 mM; 18 h) supports the detection of DNA repair synthesis in primary cultured rat hepatocytes induced by a variety of genotoxic agents. Its detection sensitivity is comparable to that of Hydroxyurea (HY-B0313) for most agents, higher for MNNG, and lower for aflatoxin B1 and H2O2[1].
Guanazole (48 h) exhibits acute toxicity to Daphnia magna, with an EC50 of 4.13 mg/L[4].
Guanazole (15-30 mM; 3 days) specifically induces replication stress in Schizosaccharomyces pombe replication checkpoint mutants (rad3Δ, cds1Δ), and its cytotoxicity against metabolic mutants (erg11-1, hem13-1) is far lower than that of hydroxyurea[3].
Guanazole (50-250 mM; 8 h) induces acute replication stress in rad3Δ Schizosaccharomyces pombe cells; due to the presence of additional stress responses, the cytotoxicity at high doses is unexpectedly reduced[3].
Guanazole (200 mM; 6 h) induces acute replication stress in Schizosaccharomyces pombe rad3Δ and cds1Δ cells, and both mutants exhibit comparable sensitivity due to additional G2/M checkpoint stress[3].
Guanazole (50-300 mM; 3 h) induces Rad3-dependent phosphorylation of Mrc1-Thr645 in wild-type Schizosaccharomyces pombe cells, and this site is a marker of replication stress[3].
Guanazole (200 mM; 6 h) induces G2/M phase cell cycle arrest accompanied by replication stress in both wild-type and rad3Δ Schizosaccharomyces pombe cells after 6 h [3].
Guanazole (200 mM; 3 h) inhibits the "cut" phenotype of premature mitosis in rad3Δ Schizosaccharomyces pombe cells, and does not induce elongation in wild-type, mrc1Δ, or erg11-1 cells. This result is consistent with G2/M cell cycle arrest[3].
Guanazole inhibits purified calf thymus ribonucleotide reductase with an IC50 of 460 μM by disrupting the tyrosyl radical of the enzyme[5].
Guanazole is an inhibitor of the ribonucleotide reductase M2 subunit, with a potency approximately one-quarter that of Hydroxyurea, and its inhibitory activity can be enhanced by iron chelators [5].
Guanazole exhibits cross-resistance in hydroxyurea-resistant Chinese hamster ovary cells and mouse L cells with upregulated or altered expression of ribonucleotide reductase[5].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:wild-type (TK48), rad3Δ, mrc1Δ, and erg11-1 Schizosaccharomyces pombe cells
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Concentration:50 mM, 100 mM, 150 mM, 200 mM, 250 mM, 300 mM
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Incubation Time:3 h
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Result:Increased Mrc1-Thr645 phosphorylation in a concentration-dependent manner in wild-type cells, with levels at 200 mM to 300 mM comparable to those in cells treated with 15 mM hydroxyurea.
Increased Mrc1 protein levels up to 150 mM, then decreased at concentrations above 150 mM.
Induced Rad3-dependent Mrc1 phosphorylation, with lower levels in erg11-1 cells compared to wild-type cells.
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Cell Line:wild-type (TK48) and rad3Δ Schizosaccharomyces pombe cells
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Concentration:200 mM
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Incubation Time:0, 1, 2, 3, 4, 5 and 6 h
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Result:Arrested wild-type and rad3Δ cells at the G2/M phase of the cell cycle throughout the 6-hour incubation period, unlike hydroxyurea treatment which caused S-phase arrest.
In Vivo
Guanazole has low acute toxicity to zebrafish embryos, with 72-hour LC50 values ranging from ≥29.70 mg/L to 17320 mg/L across replicate tests[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:DBA/2J (female, 16-18 g)[2]
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Dosage:30 mg/mL
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Administration:i.v.; 0.3 mL/hr; 47 hr
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Result:Achieved tissue levels (μg/g wet weight, ~70% of steady-state levels) of 407.6 in spleen, 398.1 in thymus, 233.3 in heart, 145.1 in brain, 248.4 in kidney, 215.9 in liver; bone marrow levels were not measurable.
Reduced 14C-uridine incorporation into DNA to 16.4% of saline control in spleen, 33.6% in thymus, 58.4% in bone marrow, 74.5% in heart, 81.4% in brain, 103.8% in kidney, and increased it to 177.0% in liver.
Reduced 14C-uridine incorporation into RNA to 43.1% of saline control in spleen, 84.3% in thymus, 91.0% in bone marrow, 82.3% in heart, and increased it to 104.3% in brain, 102.1% in kidney, 131.8% in liver.
Left total DNA content per gram of tissue unchanged across all tissues.
Chemical Information
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CAS No. 1455-77-2
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Appearance Solid
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Molecular Weight 99.09
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Formula C2H5N5
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SMILES
NC1=NN=C(N)N1
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
4°C, protect from light
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
Purity & Documentation
References
[5]. HY-W015940-3.pdf
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Guanazole Related Classifications
HY-W015940 Related Classifications
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