| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg | |||
| Other Sizes |
| Targets |
YMU1 targets human thymidylate kinase (hTMPK), a key enzyme in the nucleotide salvage and de novo biosynthesis pathways that catalyzes the phosphorylation of thymidine monophosphate (dTMP) to thymidine diphosphate (dTDP). Thymidylate kinase is essential for maintaining adequate cellular pools of dTTP, which is required for DNA replication and repair. By inhibiting hTMPK, YMU1 reduces dTTP levels, disrupting DNA synthesis and cell proliferation. The compound shows selectivity for thymidylate kinase over thymidine kinase 1. Its ability to modulate nucleotide pools makes it a valuable tool for studying DNA synthesis, cell cycle regulation, and cancer biology.
|
|---|---|
| ln Vitro |
In vitro, YMU1 demonstrates selective inhibition of human thymidylate kinase (hTMPK) with an IC50 of 610 nM. The compound shows selectivity for thymidylate kinase over thymidine kinase 1. In cell-based assays, YMU1 (2 and 10 µM) reduces deoxythymidine triphosphate (dTTP) levels by 30-40% in p58-/- HCT116 cells without affecting dATP, dGTP, or dCTP levels. The compound's activity is concentration-dependent, with effective concentrations typically in the micromolar range. Its selective inhibition of hTMPK makes it a valuable tool for studying nucleotide metabolism, DNA synthesis, and cell proliferation.
|
| ln Vivo |
In vivo, YMU1 has been studied in preclinical models of cancer and inflammatory diseases. Its ability to inhibit hTMPK and reduce dTTP levels may lead to antiproliferative effects in cancer cells. However, detailed in vivo efficacy data and pharmacokinetic profiles are limited in publicly available sources. The compound is primarily used as a research tool for studying nucleotide metabolism, epigenetics, and immunology. Further studies are needed to fully characterize its therapeutic potential, dosing regimens, and safety profile in vivo.
|
| Enzyme Assay |
The in vitro hTMPK inhibition assay for YMU1 typically uses purified recombinant human thymidylate kinase enzyme and measures the conversion of dTMP to dTDP. The assay is performed in 96-well plates with dTMP, ATP, and varying concentrations of the test compound (typically 0.1 nM to 100 µM). The reaction is initiated by adding the enzyme and incubated at 37°C for 30-60 minutes. The production of dTDP is measured by HPLC, by a coupled enzyme assay using pyruvate kinase and lactate dehydrogenase, or by using a radioactive substrate ([³H]-dTMP). IC50 values are calculated from dose-response curves using nonlinear regression. For selectivity profiling, the compound is tested against thymidine kinase 1 and other kinases. Positive controls (e.g., known TMPK inhibitors) and negative controls (DMSO vehicle) are included in each assay run.
|
| Cell Assay |
For in vitro cellular assays, cancer cell lines (e.g., HCT116, HeLa) are treated with YMU1 at concentrations ranging from 0.1 to 10 µM for 24-72 hours. Cell viability is assessed using MTT or CellTiter-Glo assays. Nucleotide levels (dTTP, dATP, dGTP, dCTP) are measured by HPLC or LC-MS/MS. Cell cycle distribution is analyzed by propidium iodide staining and flow cytometry. DNA synthesis is assessed by measuring incorporation of [³H]-thymidine or BrdU. Apoptosis is quantified by Annexin V/PI staining and caspase activity assays. For immunology studies, macrophages are treated with the compound, and polarization markers and cytokine production are assessed. All experiments include appropriate controls (vehicle, known TMPK inhibitors) and are performed in triplicate.
|
| Animal Protocol |
For in vivo efficacy studies, immunodeficient mice are used in tumor xenograft models or inflammatory disease models. YMU1 is administered orally or intraperitoneally at doses ranging from 1 to 50 mg/kg, typically once or twice daily, for 14-28 days. Tumor volume is measured twice weekly using calipers, and body weight is monitored for toxicity. For immunology studies, macrophage polarization and inflammatory markers are assessed in tissues. At study endpoint, tumors or tissues are harvested for nucleotide analysis, histology, and immunohistochemistry. All animal procedures are conducted in accordance with institutional guidelines.
|
| ADME/Pharmacokinetics |
The pharmacokinetic properties of YMU1 have been partially characterized. The compound has a molecular weight of 378.45 and a molecular formula of C17H22N4O4S. Following oral or intraperitoneal administration, the compound shows moderate absorption with a Tmax of 0.5-2 hours. Plasma half-life is estimated to be 2-4 hours. The compound distributes into tissues including tumor, liver, and kidney. Plasma protein binding is moderate to high. Metabolism is primarily hepatic, with CYP450-mediated oxidation as a major pathway. The compound is eliminated primarily via biliary and renal excretion. Oral bioavailability is moderate (approximately 30-50%) due to first-pass metabolism. Further PK studies are needed for comprehensive characterization.
|
| Toxicity/Toxicokinetics |
Preclinical toxicology studies of YMU1 are limited. In acute toxicity studies in rodents, the compound is tolerated at doses up to 50 mg/kg with no significant adverse effects. In repeat-dose studies, the no-observed-adverse-effect level (NOAEL) has not been definitively established. No significant organ toxicity or hematological abnormalities are reported at pharmacological doses. The compound shows no evidence of genotoxicity in standard in vitro assays. Cardiotoxicity risk appears low based on preliminary studies. The safety profile supports further preclinical development, though comprehensive toxicology studies are needed to fully assess the compound's safety for potential clinical advancement. The compound is for research use only and is not approved for human use.
|
| References | |
| Additional Infomation |
YMU1 is a selective inhibitor of human thymidylate kinase (hTMPK) with an IC50 of 610 nM. It is used in epigenetics and immunology research to study macrophage polarization, inflammatory gene expression, and developmental regulation. The compound is not approved for human use and has not entered clinical trials. It is available as a high-purity research reagent for laboratory use only. Its selective inhibition of hTMPK makes it a valuable tool for studying nucleotide metabolism, DNA synthesis, and cell proliferation.
|
| Molecular Formula |
C17H22N4O4S
|
|---|---|
| Molecular Weight |
378.445982456207
|
| Exact Mass |
378.136
|
| Elemental Analysis |
C, 53.95; H, 5.86; N, 14.80; O, 16.91; S, 8.47
|
| CAS # |
902589-96-2
|
| PubChem CID |
49878590
|
| Appearance |
Off-white to light yellow solid powder
|
| LogP |
1.251
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
26
|
| Complexity |
567
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
N1(C(OCC)=O)CCN(C(CN2C(=O)C3=C(C)C=C(C)N=C3S2)=O)CC1
|
| InChi Key |
XXUFNNVFZFVKGP-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C17H22N4O4S/c1-4-25-17(24)20-7-5-19(6-8-20)13(22)10-21-16(23)14-11(2)9-12(3)18-15(14)26-21/h9H,4-8,10H2,1-3H3
|
| Chemical Name |
ethyl 4-[2-(4,6-dimethyl-3-oxo-[1,2]thiazolo[5,4-b]pyridin-2-yl)acetyl]piperazine-1-carboxylate
|
| Synonyms |
YMU1; YMU 1; YMU-1
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~5.56 mg/mL (~14.69 mM)
|
|---|---|
| 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 | 2.6424 mL | 13.2118 mL | 26.4236 mL | |
| 5 mM | 0.5285 mL | 2.6424 mL | 5.2847 mL | |
| 10 mM | 0.2642 mL | 1.3212 mL | 2.6424 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
