COH000 is an allosteric, covalent and irreversible inhibitor of ubiquitin-like 1-activating enzyme (SUMO-activating enzyme) (E1), with an IC50 of 0.2 μM for SUMOylation in vitro[1].
IC50 & Target
IC50: 0.2 μM (SUMO-activating enzyme)[1].
体外研究 (In Vitro)
COH000 has over 500-fold selectivity for SUMOylation than ubiquitylation. COH000 inhibits SUMO adenylation without directly competing with ATP or SUMO1 binding. COH000 has an extremely slow off-rate and is consistent with it being covalently bound to the enzyme[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
419.47
Formula
C25H25NO5
CAS 号
1534358-79-6
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Li YJ, et al. Allosteric Inhibition of Ubiquitin-like Modifications by a Class of Inhibitor of SUMO-Activating Enzyme. Cell Chem Biol. 2018 Dec 5. pii: S2451-9456(18)30386-6.
COH29 (RNR Inhibitor COH29) is a potent ribonucleotide reductase (RNR) inhibitor with anticancer activity. COH29 inhibits α and β subunit of RNR with IC50s of 16 μM.
COH29 (RNR Inhibitor COH29) overcome hydroxyurea and gemcitabine resistance in cancer cells. It effectively inhibits proliferation of most cell lines in the NCI 60 human cancer panel, most notably ovarian cancer and leukemia, but exerts little effect on normal fibroblasts or endothelial cells. Site-directed mutagenesis, NMR and surface plasmon resonance biosensor studies confirm COH29 binding to the proposed ligand-binding pocket and offer evidence for assembly blockade of the RRM1-RRM2 quaternary structure[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
COH29 results in a dose-dependent inhibition of MOLT-4 tumor xenograft growth with twice-daily oral dosing at 50 mg/kg and 100 mg/kg, which is pronounced by Day 12 of treatment. Similarly, 7 days of treatment of mice bearing TOV11D xenografts with 200, 300, or 400 mg/kg/day COH29 results in a dose-dependent inhibition of tumor xenograft growth. Tumor growth is significantly inhibited compared with the control group[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
分子量
420.44
Formula
C22H16N2O5S
CAS 号
1190932-38-7
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Zhou B, et al. A small-molecule blocking ribonucleotide reductase holoenzyme formation inhibits cancer cell growth and overcomes drug resistance.Cancer Res. 2013 Nov 1;73(21):6484-93.
[2]. Chen MC, et al. The Novel Ribonucleotide Reductase Inhibitor COH29 Inhibits DNA Repair In Vitro. Mol Pharmacol. 2015 Jun;87(6):996-1005.
Cell Assay [1]
Cells is seeded into 96-well plates in 100 µL of complete medium at 2000 to 5000 cells per well, depending on the cell line’s growth rate. After overnight incubation, test compound is added to each well at various concentrations in 50 µL of culture medium. After a further incubation for 96 hours at 37°C, fluorescein diacetate (final concentration: 10 mg/mL) and eosin Y [final concentration: 0.1% (w/v)] is added to each well, and the cells is incubated for an additional 20 minutes at 37°C. Cytotoxicity is assessed by Digital Imaging Microscopy System detection Viability is assessed using MTS [(3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium)] as previously described[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration [1]
Female NSG mice (NOD/SCID/IL2Rgamma null) aged 8-10 weeks are supplied. Each mouse is injected with 5×106Molt-4 or TOV-112D cells subcutaneously in the right flank, and tumor volume is monitored (0.5×l×w2). After the tumors reach approximately 70 mm3, COH29 in 30% solutol is administered daily by gavage in a one or two dose schedule. Mice is sacrificed on the 28th day after cancer cell transplantation[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Zhou B, et al. A small-molecule blocking ribonucleotide reductase holoenzyme formation inhibits cancer cell growth and overcomes drug resistance.Cancer Res. 2013 Nov 1;73(21):6484-93.
[2]. Chen MC, et al. The Novel Ribonucleotide Reductase Inhibitor COH29 Inhibits DNA Repair In Vitro. Mol Pharmacol. 2015 Jun;87(6):996-1005.
COH34 is a potent and specific poly(ADP-ribose) glycohydrolase (PARG) inhibitor with an IC50 of 0.37 nM. COH34 binds to the catalytic domain of PARG (Kd=0.547 μM), thereby prolonging PARylation at DNA lesions and trapping DNA repair factors[1].
IC50 & Target
IC50: 0.37 nM (PARG)[1]
体外研究 (In Vitro)
COH34 efficiently kills PARP inhibitor-resistant cancer cells[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
COH34 induces lethality in cancer cells with DNA repair defects and exhibits antitumor activity in xenograft mouse cancer models[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
293.38
Formula
C18H15NOS
CAS 号
906439-72-3
运输条件
Room temperature in continental US; may vary elsewhere.
COH-SR4 is an AMPK activator. COH-SR4 shows potent anti-proliferative activities against leukemia, melanoma, breast and lung cancers. COH-SR4 inhibits adipocyte differentiation via AMPK activation. COH-SR4 can be used for the research of obesity and related metabolic disorders[1].
IC50 & Target
AMPK[1]
体外研究 (In Vitro)
COH-SR4 (1-5 μM; 24 hours) results in a dose-dependent increase in the phosphorylation of AMPK and its substrate ACC in 3T3-L1 preadipocytes, as well as in cancer cells such as HL-60, HeLa, MCF-7[1]. COH-SR4 (3-5 µM; 7 days) significantly inhibits 3T3-L1 adipocyte differentiation in a dose-dependent manner[1]. COH-SR4 (1-5 μM; 24 hours) promotes cell G1 cycle arrest[1]. COH-SR4 significantly reduces intracellular lipid accumulation and downregulates the expression of key adipogenesis-related transcription factors and lipogenic proteins[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Western Blot Analysis[1]
Cell Line:
3T3-L1 preadipocytes, HL-60 cells, HeLa cells, MCF-7 cells
Concentration:
1 μM, 3 μM, 5 μM
Incubation Time:
24 hours
Result:
Indirectly activated AMPK.
Cell Cycle Analysis[1]
Cell Line:
3T3-L1 cells
Concentration:
1 μM, 3 μM, 5 μM
Incubation Time:
24 hours
Result:
Modulated the level of proteins active during S and G2 phases of the cell cycle.
体内研究 (In Vivo)
COH-SR4 (5 mg/kg; i.g.; 3x/week; for 6 weeks) reduces body weight and fat mass in high fat diet (HFD) obese mice without affecting food intake[2]. COH-SR4 improves glycemic control and dyslipidemia in HFD obese mice[2]. COH-SR4 decreases adipose tissue hypertrophy and affects circulating adipokine levels in HFD obese mice[2]. COH-SR4 prevents hepatic lipid accumulation and fatty liver in HFD obese mice[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
Nine-week old male C57BL/6J mice[2]
Dosage:
5 mg/kg
Administration:
Oral gavage, three times a week, for 6 weeks
Result:
Decreased body weight and fat mass in HFD obese mice.
分子量
350.03
Formula
C13H8Cl4N2O
CAS 号
73439-19-7
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. James L Figarola, et al. Small‑molecule COH-SR4 inhibits adipocyte differentiation via AMPK activation. Int J Mol Med. 2013 May;31(5):1166-76.
[2]. James Lester Figarola, et al. COH-SR4 Reduces Body Weight, Improves Glycemic Control and Prevents Hepatic Steatosis in High Fat Diet-Induced Obese Mice. PLoS One. 2013; 8(12): e83801.
