| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
TAS-1553 targets ribonucleotide reductase (RNR), specifically by disrupting the protein-protein interaction between the R1 and R2 subunits. RNR is a key enzyme in DNA synthesis that catalyzes the conversion of ribonucleotides to deoxyribonucleotides. The enzyme binds to the R1 subunit with Kd of 34.9 nM and has an enzyme IC50 of 54.2 nM. By inhibiting RNR, TAS-1553 reduces dATP pools and inhibits DNA replication, leading to apoptosis.
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| ln Vitro |
The enzymatic activity of RNR is dose-dependently inhibited by TAS1553 (0.001-1 μM) [1]. With GI50 values ranging from 0.228 to 4.15 μM, TAS1553 (3 d) exhibits antiproliferative action against both solid and hematological human cancer cell lines [1]. In a dose- and time-dependent way, TAS1553 (1-10 μM; 0-2 hours; HCC38 and MV-4-11 cells) lowers the intracellular pool of dATP, a crucial metabolite for DNA replication [1]. In HCC38 and MV-4-11 cells, TAS1553 (0-10 μM; 0-24 hours) promotes apoptosis and replication stress in a dose- and time-dependent manner [1].
In vitro, TAS-1553 inhibits RNR with an enzyme IC50 of 54.2 nM and binds to the R1 subunit with Kd of 34.9 nM. It inhibits protein-protein interaction with IC50 = 0.0396 μM. It exhibits antiproliferative action against both solid and hematological human cancer cell lines with GI50 values ranging from 0.228 to 4.15 µM. It inhibits DNA replication, reduces intracellular dATP pools, and induces apoptosis. |
| ln Vivo |
RNR inhibitory effects have been observed in vivo for TAS1553 (25-200 mg/kg; oral; for 24 hours; female F344/NJcl-rnu/rnu rats and BALB/cAJcl-nu/nu mice) [1]. In vivo anti-tumor activity has been demonstrated for TAS1553 (50-200 mg/kg; oral; daily for 15 d; female F344/NJcl-rnu/rnu rats and BALB/cAJcl-nu/nu mice) [1].
In vivo, TAS-1553 is orally active and has shown anti-tumor activity in preclinical models. It inhibits DNA replication and induces apoptosis. Specific in vivo efficacy data are limited in publicly available sources. The compound is being studied for cancer research applications. |
| Enzyme Assay |
In vitro enzyme assays for RNR inhibition are used to characterize TAS-1553's activity. RNR enzyme is incubated with the compound, and the conversion of ribonucleotides to deoxyribonucleotides is measured. IC50 = 54.2 nM. Binding to the R1 subunit is assessed by surface plasmon resonance or other binding assays (Kd = 34.9 nM). PPI inhibition is measured by assays detecting R1-R2 subunit interaction (IC50 = 0.0396 μM).
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: HCC38 and MV-4-11 Cell Tested Concentrations: 0, 0.1, 0.3, 1, 3 and 10 μM Incubation Duration: 0, 1, 2, 4, 8 and 24 hrs (hours) Experimental Results: Increased Ser345 , expression of Ser4, Ser8 and Thr21 phosphorylation. Increased levels of cleaved PARP and cleaved caspase-3. Cell-based assays for TAS-1553 are conducted in cancer cell lines. Cells are treated with the compound at various concentrations (GI50 = 0.228-4.15 µM). DNA replication is assessed by BrdU incorporation or EdU labeling. Intracellular dATP levels are measured by HPLC or mass spectrometry. Apoptosis is assessed by Annexin V/PI staining and caspase activation. |
| Animal Protocol |
Animal/Disease Models: Female F344/NJcl-rnu/rnu rats and BALB/cAJcl-nu/nu (nude) mice [1]
Doses: 25, 50, 100 and 200 mg/kg Route of Administration: Oral; 200 mg/kg. 24 hour Experimental Results: diminished intracellular dATP pools and induced replicative stress and apoptosis. Animal/Disease Models: Female F344/NJcl-rnu/rnu rats and BALB/cAJcl-nu/nu (nude) mice [1] Doses: 50, 100 and 200 mg/kg Route of Administration: po (po (oral gavage)) one time/day for 15 days. Experimental Results: The tumor growth inhibition rates (T/C) of the treatment group/control group were 52.0 (50mg/kg), 45.0 (100mg/kg) and 29.4% (200mg/kg) respectively. In vivo animal experiments with TAS-1553 are conducted in xenograft models. The compound is administered orally, and tumor growth inhibition is assessed. DNA replication inhibition and apoptosis are evaluated in tumor tissues. Specific protocols are not extensively documented. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of TAS-1553 include oral activity. The compound is designed for oral administration. Specific PK parameters such as half-life, Cmax, and bioavailability have not been extensively reported. Storage: appropriately.
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| Toxicity/Toxicokinetics |
TAS-1553 has demonstrated antiproliferative activity against cancer cell lines. Safety and toxicology data are limited. The compound is for research use only and is not approved for human therapeutic use. Standard laboratory safety precautions should be followed when handling the compound.
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| References |
[1]. Ueno H, et, al. TAS1553, a small molecule subunit interaction inhibitor of ribonucleotide reductase, exhibits antitumor activity by causing DNA replication stress. Commun Biol. 2022 Jun 9;5(1):571.
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| Additional Infomation |
TAS-1553 has CAS number 2166023-31-8. It is a potent, orally active PPI inhibitor of RNR with IC50 = 0.0396 μM. It inhibits RNR with enzyme IC50 = 54.2 nM and binds R1 with Kd = 34.9 nM. It inhibits DNA replication, reduces dATP, and induces apoptosis. Not for human use; for research purposes only.
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| Molecular Formula |
C20H20CLFN4O5S
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| Molecular Weight |
482.913005828857
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| Exact Mass |
482.082
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| CAS # |
2166023-31-8
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| PubChem CID |
132203319
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| Appearance |
White to off-white solid powder
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| LogP |
3.1
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| Hydrogen Bond Donor Count |
3
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
32
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| Complexity |
867
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| Defined Atom Stereocenter Count |
2
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| SMILES |
CC1=C(C(=C(C=C1)F)[C@@H](C)[C@@H](C2=NNC(=O)O2)NS(=O)(=O)C3=C(C=C(C=C3)Cl)C(=O)N)C
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| InChi Key |
DUYRWEBTZNUILI-DIFFPNOSSA-N
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| InChi Code |
InChI=1S/C20H20ClFN4O5S/c1-9-4-6-14(22)16(10(9)2)11(3)17(19-24-25-20(28)31-19)26-32(29,30)15-7-5-12(21)8-13(15)18(23)27/h4-8,11,17,26H,1-3H3,(H2,23,27)(H,25,28)/t11-,17+/m1/s1
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| Chemical Name |
5-chloro-2-[[(1S,2R)-2-(6-fluoro-2,3-dimethylphenyl)-1-(2-oxo-3H-1,3,4-oxadiazol-5-yl)propyl]sulfamoyl]benzamide
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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 (~207.08 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.18 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.18 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0708 mL | 10.3539 mL | 20.7078 mL | |
| 5 mM | 0.4142 mL | 2.0708 mL | 4.1416 mL | |
| 10 mM | 0.2071 mL | 1.0354 mL | 2.0708 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.
Link: https://clinicaltrials.gov/ct2/show/NCT04637009
Conditions:Acute Myeloid Leukemia|Myeloproliferative Neoplasm|Myelodysplastic/Myeloproliferative NeoplasmProducts are for research use only; We do not sell to patients
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