| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg | |||
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| 500mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
RNR ( IC50 = 8 μM ); RNR ( IC90 = 31.57±3.35 μM )
COH29 targets ribonucleotide reductase (RNR), a key enzyme that catalyzes the conversion of ribonucleotides to deoxyribonucleotides, which are essential for DNA synthesis. It acts as an inhibitor, binding to the RNR enzyme and preventing its activity. By inhibiting RNR, it blocks DNA replication and inhibits tumor cell proliferation. |
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| ln Vitro |
COH29, an RNR inhibitor, counteracts the effects of gemcitabine and hydroxyurea. It has little effect on normal fibroblasts or endothelial cells, but it significantly reduces intermittent growth in most cell lines in the NCI 60 human cancer panel, most notably advanced malignancies and lymphocytes. The ligand binding pocket of COH29-binding defense was confirmed by site-directed mutagenesis, NMR, and surface barrier biosensor investigations, which also offered proof for the assembly of the RRM1-RRM2 quaternary structure [1].
In vitro, COH29 inhibits recombinant RNR small subunit (RRM1/RRM2) activity with an IC50 of 16 µM. It inhibits the α and β subunits of RNR with IC50s of 16 µM. It is a potent inhibitor of RNR with anticancer activity. |
| ln Vivo |
On day 12 of therapy, COH29 was found to cause a dose-dependent suppression of the growth of MOLT-4 xenograft tumors at twice daily tumor doses of 50 mg/kg and 100 mg/kg. Similarly, dose-inhibitory factors of xenograft tumor growth were obtained by treating TOV11D-labeled xenograft tumor models with 200, 300, or 400 mg/kg/day COH29 for seven days. Factors considerably decreased tumor growth in comparison to the control group [1].
In vivo, COH29 is orally bioavailable. It has potential antineoplastic activity. Upon oral administration, it inhibits RNR-catalyzed deoxyribonucleotide synthesis, inhibiting DNA replication and tumor cell proliferation. |
| Enzyme Assay |
COH29 is evaluated in cell-free enzymatic assays using purified RNR enzyme. The compound is incubated with RNR and a substrate, and the inhibition of enzyme activity is measured. IC50 values are determined to quantify the potency of RNR inhibition.
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| Cell Assay |
Depending on the rate of growth of the cell line, 2000–5000 cells are seeded into each well of 96-well plates using 100 µL of complete medium. Following an overnight incubation period, 50 µL of culture medium containing varying concentrations of the test compound is added to each well. Following a 96-hour incubation period at 37°C, each well is supplemented with 10 mg/mL of fluorescein diacetate and 0.1% (w/v) of eosin Y. The cells are then incubated for a further 20 minutes at 37°C. Digital Imaging Microscopy System detection is used to evaluate cytotoxicity. MTS [(3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium)] is used to evaluate viability, as previously mentioned[1].
COH29 is assessed in cell-based assays using cancer cell lines. Cells are treated with COH29, and cell proliferation, DNA synthesis, and RNR activity are measured. The compound's ability to inhibit RNR and block DNA replication is evaluated. |
| Animal Protocol |
NSG mice, female, 8–10 week old, NOD/SCID/IL2Rgamma null. The tumor volume (0.5×l×w2) of each mouse is tracked after subcutaneous injection of 5×106Molt-4 or TOV-112D cells in the right flank. COH29 in 30% solutol is given through gavage once or twice a day in doses once the tumors get to be about 70 mm3. After transplanting cancer cells, mice are killed on day 28[1].
COH29 is administered orally in animal models to evaluate its antitumor efficacy. It is orally bioavailable. Efficacy is assessed by measuring tumor growth inhibition and DNA synthesis. Its potential antineoplastic activity is evaluated. |
| ADME/Pharmacokinetics |
COH29 has a molecular weight of 420.44 and a molecular formula of C22H16N2O5S. It has a CAS number of 1190932-38-7. The compound is an orally available, aromatically substituted thiazole. It should be stored in a dry, dark place.
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| Toxicity/Toxicokinetics |
No detailed toxicity data is available for COH29. The compound is for research use only and is not intended for human therapeutic use. It is a potent RNR inhibitor used to study cancer and DNA replication.
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| References | |
| Additional Infomation |
The RNR inhibitor CoH29 is an orally potent aromatic substituted thiazole compound that inhibits human ribonucleotide reductase (RNR) and possesses potential antitumor activity. After oral administration, the RNR inhibitor CoH29 binds to the ligand-binding pocket near the C-terminal tail of the RNR M2 subunit (hRRM2). This blocks the interaction between the hRRM1 and hRRM2 subunits and interferes with the assembly of the RNR-active hRRM1/hRRM2 complex. Inhibition of RNR activity reduces the pool of deoxyribonucleoside triphosphates (dNTPs) available for DNA synthesis. This reduction in DNA synthesis leads to cell cycle arrest and growth inhibition. Furthermore, the drug may also inhibit ribozyme polymerase (ADP-ribose) 1, thereby preventing DNA damage repair, leading to the accumulation of single-stranded and double-stranded DNA breaks and the induction of apoptosis. RNR is an enzyme that catalyzes the conversion of ribonucleoside diphosphate to deoxyribonucleoside diphosphate. It is essential for de novo DNA synthesis and plays an important role in cell growth. It is overexpressed in many cancer cell types and is associated with increased drug resistance, cancer cell growth, and metastasis.
COH29 is also known as RNR Inhibitor COH29. It is an orally available, aromatically substituted thiazole inhibitor of human ribonucleotide reductase (RNR). It has potential antineoplastic activity. The compound is not approved for clinical use. |
| Molecular Formula |
C22H16N2O5S
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|---|---|
| Molecular Weight |
420.439
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| Exact Mass |
420.078
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| Elemental Analysis |
C, 62.85; H, 3.84; N, 6.66; O, 19.03; S, 7.63
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| CAS # |
1190932-38-7
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| Related CAS # |
1190932-38-7
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| PubChem CID |
44253415
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
4.624
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
30
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| Complexity |
590
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S1C(N([H])C(C2C([H])=C([H])C(=C(C=2[H])O[H])O[H])=O)=NC(C2C([H])=C([H])C(=C(C=2[H])O[H])O[H])=C1C1C([H])=C([H])C([H])=C([H])C=1[H]
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| InChi Key |
LGGDLPSXAGQFSG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H16N2O5S/c25-15-8-6-13(10-17(15)27)19-20(12-4-2-1-3-5-12)30-22(23-19)24-21(29)14-7-9-16(26)18(28)11-14/h1-11,25-28H,(H,23,24,29)
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| Chemical Name |
N-[4-(3,4-dihydroxyphenyl)-5-phenyl-1,3-thiazol-2-yl]-3,4-dihydroxybenzamide
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| Synonyms |
COH29; COH-29; COH 29
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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: 40~50 mg/mL (95.1~118.9 mM)
Ethanol: 10 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.95 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 (5.95 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.95 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 5 mg/mL (11.89 mM) in 30% Polyethylene glycol 12-hydroxystearate in Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3785 mL | 11.8923 mL | 23.7846 mL | |
| 5 mM | 0.4757 mL | 2.3785 mL | 4.7569 mL | |
| 10 mM | 0.2378 mL | 1.1892 mL | 2.3785 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT02112565 | Active Recruiting |
Drug: RNR inhibitor COH29 Other: pharmacological study |
Unspecified Adult Solid Tumor, Protocol Specific |
City of Hope Medical Center | June 13, 2016 | Phase 1 |
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