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| Targets |
IC50: 1.6 μM (MTHFD2), >30 μM (MTHFD1)[1].
DS44960156 selectively targets methylenetetrahydrofolate dehydrogenase 2 (MTHFD2), a mitochondrial enzyme in the folate-dependent one-carbon metabolism pathway. MTHFD2 catalyzes the conversion of 10-formyl-tetrahydrofolate to tetrahydrofolate, providing one-carbon units for nucleotide synthesis. DS44960156 inhibits MTHFD2 with an IC50 of 1.6 μM and a Ki of 1.23 μM. It is selective for MTHFD2 over the cytoplasmic isoform MTHFD1, with an IC50 of >30 μM for MTHFD1. By inhibiting MTHFD2, the compound disrupts nucleotide synthesis and impairs cancer cell proliferation. |
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| ln Vitro |
DS44960156 demonstrates potent in vitro inhibition of MTHFD2 with an IC50 of 1.6 μM and a Ki of 1.23 μM. The compound is selective for MTHFD2 over MTHFD1, with an IC50 of >30 μM for MTHFD1. DS44960156 was discovered via high-throughput screening and optimized using structure-based drug design. The compound features a tricyclic coumarin scaffold. Its inhibition of MTHFD2 disrupts one-carbon metabolism and nucleotide synthesis, leading to antiproliferative effects in cancer cells. These in vitro findings support the compound's potential as a cancer therapeutic.
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| ln Vivo |
In vivo activity data for DS44960156 are not extensively documented in the available literature. The compound is described as a selective MTHFD2 inhibitor for cancer research. Its discovery via high-throughput screening and optimization using structure-based drug design suggests that it has been evaluated in preclinical models. Standard in vivo efficacy studies would involve mouse xenograft models of cancers that depend on MTHFD2 activity. Further studies are needed to fully characterize the compound's efficacy, pharmacokinetics, and safety in animal models.
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| Enzyme Assay |
The in vitro enzyme assay for DS44960156 involves measuring its inhibition of MTHFD2 and MTHFD1 enzymatic activities. Recombinant human MTHFD2 and MTHFD1 are expressed and purified. Enzyme activity is assessed by spectrophotometrically monitoring the conversion of 10-formyl-tetrahydrofolate to tetrahydrofolate, coupled to the reduction of NADP+ to NADPH. DS44960156 is incubated with the enzyme and substrate at various concentrations. IC50 values are determined by fitting the inhibition data to a dose-response curve. The assay buffer typically contains Tris-HCl and appropriate cofactors.
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| Cell Assay |
In vitro cellular assays for DS44960156 typically use cancer cell lines that depend on MTHFD2 activity for proliferation. Cells are treated with DS44960156 at various concentrations for 48-72 hours. Cell viability is measured using standard assays such as MTT, CellTiter-Glo, or trypan blue exclusion. The compound's ability to inhibit cell proliferation is quantified as the half-maximal inhibitory concentration (IC50). Additionally, the effects on nucleotide synthesis and one-carbon metabolism can be assessed by metabolomic analysis. These assays confirm the compound's cellular activity and support its use in cancer research.
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| Animal Protocol |
In vivo animal experiments for DS44960156 are not extensively documented. As a selective MTHFD2 inhibitor for cancer research, standard in vivo efficacy studies would involve mouse xenograft models of MTHFD2-dependent cancers. Tumor-bearing mice would be administered DS44960156 via oral or parenteral routes. Tumor growth would be monitored, and tissues would be collected for analysis of MTHFD2 inhibition, one-carbon metabolism, and biomarkers of cell proliferation. Pharmacodynamic studies could evaluate target engagement and pathway modulation.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of DS44960156 are not extensively documented. As a small-molecule MTHFD2 inhibitor with a molecular weight of 349.34, the compound is expected to have reasonable bioavailability. Its tricyclic coumarin scaffold may influence its absorption, distribution, metabolism, and excretion (ADME) properties. The compound's discovery via high-throughput screening and optimization using structure-based drug design suggests that drug-like properties have been considered. Further pharmacokinetic studies are needed to fully characterize its PK profile.
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| Toxicity/Toxicokinetics |
Toxicological data for DS44960156 are not extensively available in the public domain. As a research compound used for cancer studies, DS44960156 has not undergone extensive toxicological evaluation. Standard cytotoxicity assays in cancer cell lines are typically performed to assess antiproliferative effects. In animal studies, tolerability and potential adverse effects would be monitored. Further preclinical toxicology studies would be required to assess safety, determine no-observed-adverse-effect levels (NOAEL), and evaluate potential off-target effects before clinical development.
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| References | |
| Additional Infomation |
DS44960156 is a selective MTHFD2 inhibitor with an IC50 of 1.6 μM for MTHFD2 and >30 μM for MTHFD1. It was discovered via high-throughput screening and optimized using structure-based drug design. The compound features a tricyclic coumarin scaffold and is used in cancer research. It has a molecular weight of 349.34 and formula C20H15NO5. No clinical trials or regulatory approvals have been reported. DS44960156 is available as a research-grade compound.
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| Molecular Formula |
C20H15NO5
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|---|---|
| Molecular Weight |
349.34
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| Exact Mass |
349.095
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| CAS # |
2361327-08-2
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| PubChem CID |
138393352
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| Appearance |
White to off-white solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
652.9±55.0 °C at 760 mmHg
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| Flash Point |
348.7±31.5 °C
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| Vapour Pressure |
0.0±2.1 mmHg at 25°C
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| Index of Refraction |
1.700
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| LogP |
2.71
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
26
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| Complexity |
647
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1CN(CC2=C1C3=CC=CC=C3OC2=O)C(=O)C4=CC=C(C=C4)C(=O)O
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| InChi Key |
OXUKTNZACAKVRG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H15NO5/c22-18(12-5-7-13(8-6-12)19(23)24)21-10-9-14-15-3-1-2-4-17(15)26-20(25)16(14)11-21/h1-8H,9-11H2,(H,23,24)
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| Chemical Name |
4-(5-oxo-2,4-dihydro-1H-chromeno[3,4-c]pyridine-3-carbonyl)benzoic acid
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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) |
DMSO: 100 mg/mL (286.25 mM)
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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 | 2.8625 mL | 14.3127 mL | 28.6254 mL | |
| 5 mM | 0.5725 mL | 2.8625 mL | 5.7251 mL | |
| 10 mM | 0.2863 mL | 1.4313 mL | 2.8625 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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