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Whole Cell Screening - Contract Research Services
These Contract Research Services are also reported in the section dedicated to "Nucleotide Analysis Services" section and refered as "Mechanism Of Action by Nucleotide Profiling".
These Contract Research Services are also reported in the section dedicated to "Nucleotide Analysis Services" section and refered as "Mechanism Of Action by Nucleotide Profiling".
NOVOCIB has developed a range of Nucleotide Profiling Services based on an accurate quantification by HPLC of more than 31 cellular (deoxy-) ribonucleotides (mono-, di-, and triphosphate) and nucleotide co-factors in drug-treated cells.
These analytical services were validated with a wide range of recognized inhibitors of nucleotide biosynthesis: MPA, hydroxyurea, methotrexate, ribavirin, mizoribine, leflunomide, gemcitabine… These reference drugs do impact differently on nucleotide metabolism, each showing its own mode of action through a specific nucleotide profile, which is used as a metabolic signature.
Any new compound's mode of action can be analyzed by establishing its nucleotide profile which is then compared with the profiles obtained with reference drugs.
| Assays | Targeted Enzyme(s)
/ Targeted Biosynthetic Pathway |
Reference Drugs (examples) |
| IMPDH inhibition:
Whole Cell Screening |
Inosine Monophosphate Dehydrogenase
(IMPDH) |
Ribavirin
MPA (Mycophenolic Acid) |
| RNR inhibition
Whole Cell Screening |
RNR (Ribonucleotide Reductase) | HU (Hydroxyurea
Gemcitabine |
| Multi-targeted Antifolates:
Whole Cell Screening |
• de novo Purine biosynthesis enzymes:
GAR transformylase, AICAR transformylase • Thymidylate Synthase (TS) |
MTX
(Methotrexate) |
These analytical services were validated with a wide range of recognized inhibitors of nucleotide biosynthesis: MPA, hydroxyurea, methotrexate, ribavirin, mizoribine, leflunomide, gemcitabine… These reference drugs do impact differently on nucleotide metabolism, each showing its own mode of action through a specific nucleotide profile, which is used as a metabolic signature.
Any new compound's mode of action can be analyzed by establishing its nucleotide profile which is then compared with the profiles obtained with reference drugs.
Other nucleotide analyses are available. Please, see also our Customized Nucleotide Profiling Analysis
IMPDH inhibition: Whole Cell Screening
Aim: This Research Contract Service has been specially tailored to validate Inosine Monophosphate Dehydrogenase (IMPDH) inhibition by a given compound in cultured cells. The assay consists in extracting, identifying and quantifying by HPLC the intracellular concentration of guanosine nucleotides (GMP, GDP and GTP) and IMP in cells treated by a compound.
Whole Cell Screening for IMPDH Inhibition was validated with mycophenolic acid (MPA), ribavirin and mizoribin, recognized inhibitors of IMPDH. When applied for the study of nucleoside analogues (NA), this assay can also reveal the formation of their mono-, di-, and triphosphate forms, indicating that nucleoside analogues enter the cells and are readily phosphorylated by cellular kinases.
Whole Cell Screening for IMPDH Inhibition was validated with mycophenolic acid (MPA), ribavirin and mizoribin, recognized inhibitors of IMPDH. When applied for the study of nucleoside analogues (NA), this assay can also reveal the formation of their mono-, di-, and triphosphate forms, indicating that nucleoside analogues enter the cells and are readily phosphorylated by cellular kinases.
To know more about NovoCIB's IMPDH inhibition: Whole Cell Screening
RNR inhibition: Whole Cell Screening (^Top)
Aim: This Research Contract Service has been specially tailored to validate Ribonucleotide Reductase (RNR) inhibition by a given compound in cultured cells. The assay consists in extracting, identifying and quantifying by HPLC the intracellular concentration of deoxynucleotides di- and triphosphate in cells treated by a compound.
Whole Cell Screening for RNR Inhibition was validated with hydroxyurea and gemcitabine in HeLa cultured cells.
Whole Cell Screening for RNR Inhibition was validated with hydroxyurea and gemcitabine in HeLa cultured cells.
To know more about NovoCIB's RNR inhibition: Whole Cell Screening
Multi-targeted Antifolates: Whole Cell Screening (^Top)
Aim: This Research Contract Service has been specially tailored to validate inhibition of de novo biosynthesis of purine and pyrimidne nucleotides by a given compound in cultured cells. After incubation of cultured cells with the inhibitor, nucleotides are extracted, separated, identified and quantified by UV-HPLC.
Whole Cell Screening for Multi-targeted Antifolates was validated with methotrexate in HeLa cultured cells.
Whole Cell Screening for Multi-targeted Antifolates was validated with methotrexate in HeLa cultured cells.
To know more about NovoCIB's Multi-targeted antifolates: Whole Cell Screening