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| Targets |
BAY-707 is a substrate-competitive, highly potent, and selective inhibitor of MTH1 (NUDT1). MTH1 (MutT homolog 1) is a nucleotide pool sanitization enzyme that hydrolyzes oxidized nucleotides to prevent their incorporation into DNA. By inhibiting MTH1, BAY-707 prevents the removal of oxidized nucleotides, leading to DNA damage and cell death in cancer cells.
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| ln Vitro |
EC50 of 7.6 nM for BAY-707 indicates good cellular target binding, which is in line with its strong enzymatic efficacy (IC50=2.3 nM) [1]. In the Caco-2 experiment, BAY-707 demonstrates high cell permeability with an efflux rate of 288 nm/s[1]. In vitro studies using human microsomes (0.29L/h/kg, Fmax=78%) and rat hepatocytes (0.54L/h/kg, Fmax=87) demonstrate BAY-707's generally good physicochemical features as well as its strong metabolic stability and pharmacokinetic qualities. %)[1]. On HMEC, HeLa, and SW-480 cells, BAY-707 (0-30 μM; 24 hours) had no antiproliferative effect [1].
In vitro, BAY-707 potently inhibits MTH1 with an IC50 of 2.3 nM. It demonstrates strong cellular target engagement with an EC50 of 7.6 nM. It shows high permeability in Caco-2 assays. Despite its potent biochemical activity, BAY-707 shows a clear lack of in vitro anticancer efficacy. This suggests that MTH1 inhibition alone may not be sufficient for anticancer activity. |
| ln Vivo |
Bay-077 (oral administration; 50-250 mg/kg; 2 weeks) shows better pharmacokinetic properties, biochemical potency, and cellular target engagement as compared to previous MTH1 tool compounds; nonetheless, neither the medication nor the combination therapy demonstrated anticancer activity for Bay-077. combination therapy using NCI-H460 and CT26 mice models [1]. In nude mice, BAY-707 (oral; 50–250 mg/kg; 2 weeks) was well tolerated, and after 7 days of therapy, the body weight loss did not exceed 10% [1].
In vivo, BAY-707 is well-tolerated in mice. It has favorable pharmacokinetic profiles compared with other MTH1 compounds. However, it demonstrates a distinct lack of in vivo anticancer efficacy. This has important implications for the development of MTH1 inhibitors as anticancer therapeutics and suggests that MTH1 may not be a viable target for cancer treatment. |
| Enzyme Assay |
In vitro enzyme assays for BAY-707 typically involve measuring the inhibition of recombinant human MTH1 (NUDT1) enzyme. The enzyme is incubated with varying concentrations of the compound and a substrate (e.g., 8-oxo-dGTP). Activity is measured by monitoring the hydrolysis of the substrate or by coupled enzyme assays. IC50 values are calculated from dose-response curves.
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| Cell Assay |
Cell-based assays for BAY-707 involve culturing cancer cell lines in appropriate media. Cells are treated with BAY-707 at concentrations ranging from 0.1 nM to 10 µM for 24-72 hours. Cell viability is assessed by MTT or CellTiter-Glo assays. Cellular target engagement is measured by CETSA (cellular thermal shift assay) or NanoBRET. DNA damage is evaluated by comet assay or γ-H2AX staining.
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| Animal Protocol |
In vivo animal experiments for BAY-707 typically involve administration to tumor-bearing mice via oral gavage or intraperitoneal injection. Tumor growth inhibition is monitored. Pharmacokinetic parameters are evaluated by measuring compound levels in blood and tissues. Target engagement is assessed by measuring MTH1 inhibition in tumor tissues. Toxicity is assessed by monitoring body weight, organ histology, and clinical chemistry parameters.
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| ADME/Pharmacokinetics |
BAY-707 (molecular weight ~280-300, formula C15H20N4O2) has favorable pharmacokinetic properties, including high metabolic stability in human microsomes and rat hepatocytes. It shows high permeability in Caco-2 assays. It is well-tolerated in mice. Detailed pharmacokinetic parameters including absorption, distribution, metabolism, and excretion are available in preclinical literature.
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| Toxicity/Toxicokinetics |
BAY-707 is well-tolerated in mice. No significant toxicity has been reported in preclinical studies. However, comprehensive toxicological evaluation including acute, subchronic, and genotoxicity studies may have been conducted. The compound is for research use only and not intended for therapeutic use. Standard laboratory safety precautions should be followed.
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| References | |
| Additional Infomation |
Structure in the first source
BAY-707 (CAS#: 2109805-96-9) is a substrate-competitive, highly potent, and selective MTH1 (NUDT1) inhibitor (IC50 = 2.3 nM). It has strong cellular target engagement (EC50 = 7.6 nM) and favorable PK properties. It shows a lack of anticancer efficacy. It is a research tool for studying MTH1 biology. Molecular weight ~280-300, formula C15H20N4O2. |
| Molecular Formula |
C15H20N4O2
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|---|---|
| Molecular Weight |
288.344902992249
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| Exact Mass |
288.158
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| CAS # |
2109805-96-9
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| Related CAS # |
2223023-19-4 (acetate);2109805-96-9;
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| PubChem CID |
129012086
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| Appearance |
White to yellow solid powder
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| Density |
1.2±0.1 g/cm3
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| Index of Refraction |
1.608
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| LogP |
1.65
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
21
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| Complexity |
379
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CCNC(=O)C1=CC2=C(C=CN=C2N1)N3CCOC[C@@H]3C
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| InChi Key |
RPMGXDCRCWWCRY-JTQLQIEISA-N
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| InChi Code |
InChI=1S/C15H20N4O2/c1-3-16-15(20)12-8-11-13(4-5-17-14(11)18-12)19-6-7-21-9-10(19)2/h4-5,8,10H,3,6-7,9H2,1-2H3,(H,16,20)(H,17,18)/t10-/m0/s1
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| Chemical Name |
N-ethyl-4-[(3S)-3-methylmorpholin-4-yl]-1H-pyrrolo[2,3-b]pyridine-2-carboxamide
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.4681 mL | 17.3406 mL | 34.6813 mL | |
| 5 mM | 0.6936 mL | 3.4681 mL | 6.9363 mL | |
| 10 mM | 0.3468 mL | 1.7341 mL | 3.4681 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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