GLPBio

Theaflavine-3,3'-digallate

Catalog No.: GN10817Purity:>98%
COASDSData Sheet
Theaflavine-3,3'-digallate is a bioactive tea polyphenol compound. It is an effective inhibitor of the Zika virus (ZIKV) protease with an IC50 of 2.3 μM.

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Theaflavine-3,3'-digallate
Cas No.: 33377-72-9
10mM (in 1mL DMSO)In Stock
$236.00
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1mgIn Stock
$63.00
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5mgIn Stock
$155.00
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10mgIn Stock
$234.00
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25mgIn Stock
$375.00
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50mgIn Stock
$515.00
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Description

Theaflavine-3,3'-digallate is a bioactive tea polyphenol compound. It is an effective inhibitor of the Zika virus (ZIKV) protease with an IC50 of 2.3 μM [1]. Theaflavine-3,3'-digallate directly binds to ZIKVpro (Kd = 8.86μM) and inhibits ZIKV replication. Theaflavine-3,3'-digallate can inhibit the activities of gp41 and NS2B-3 proteases and has antiviral activities against HSV and HIV-1 [2]. Theaflavine-3,3'-digallate is an effective anti-tumor agent and can also be used to study the regulatory effect of intestinal microbiota composition [3].

In vitro, Theaflavine-3,3'-digallate (5-30μM; 3, 72h) pretreatment exhibits growth inhibitory effects on HCT116 cells in a dose- and time-dependent manner, leading to cell cycle arrest and induction of apoptosis, and inhibiting COX-2, iNOS, and ERK1/2 expression [5]. Theaflavine-3,3'-digallate (0-20μM; 6 days) treatment dose-dependently increases the sensitivity of SNU-216 and NCI-N87 cells to trastuzumab (Trast) and reduces cell proliferation [6].

In vivo, Theaflavine-3,3'-digallate (50mg/kg/day; 21 days; i.p.) combined with trastuzumab treatment significantly inhibits tumor growth in xenograft mice carrying NCI-N87 tumor cells and induces a sharp regression of tumors, effectively blocking SHCBP1 nuclear translocation and inhibiting MISP phosphorylation [6].

References:
[1] Cui X, Zhou R, Huang C, et al. Identification of Theaflavin-3,3'-Digallate as a Novel Zika Virus Protease Inhibitor. Front Pharmacol. 2020;11:514313. Published 2020 Oct 21.
[2] Lian Y, Huang Z, Liu X, et al. Discovery of Ten Anti-HIV Hit Compounds and Preliminary Pharmacological Mechanisms Studies[J]. Current HIV Research, 2024, 22(2): 82-90.
[3] Xue Z, Junli Y I N, Jiaxiang W, et al. Research Progress on Anti-Tumor Mechanism of Theaflavins Natural Products[J]. Cancer Research on Prevention and Treatment, 2022, 49(8): 820-826. 
[4] Qu F, Liu S, He C, et al. Comparison of the effects of green and black tea extracts on Na+/K+‐ATPase activity in intestine of type 1 and type 2 diabetic mice[J]. Molecular nutrition & food research, 2019, 63(17): 1801039.
[5] Ding Y, Chen B, Gao Z, Suo H, Xiao H. Pre-treated theaflavin-3,3'-digallate has a higher inhibitory effect on the HCT116 cell line. Food Nutr Res. 2017 Nov 15;61(1):1400340. 
[6] Shi W, Zhang G, Ma Z, et al. Hyperactivation of HER2-SHCBP1-PLK1 axis promotes tumor cell mitosis and impairs trastuzumab sensitivity to gastric cancer[J]. Nature Communications, 2021, 12(1): 2812.

Protocol

Kinase experiment [1]:

Preparation Method

Mixtures of Na+/K+-ATPase enzyme, Tris-buffer (containing 1mM ouabain or not), and different concentrations of Theaflavine-3,3’-digallate were preincubated at 37°C as the method of the Na+/K+-ATPase activity assay. Increasing concentrations of the substrate ATP in the range of 2.0–5.0mM were added to estimate the ATP kinetics of Na+/K+-ATPase. After incubation for 60min at 37°C, 200µL of trichloroacetic acid was added to terminate the reaction, and the liberated inorganic phosphorus was determined by a phosphate assay kit. The Vmax and Km constants were determined using Lineweaver–Burk plots generated from the relevant Michaelis–Menten equations. The Na+/K+-ATPase kinetics for the Na+ or K+ cofactors were determined by the same method in the presence of increasing concentrations of NaCl or KCl in the range of 1.0–8.0mM or 0.5–4.0mM. The amount of ATP was constant (5mM).

Reaction Conditions

0-30μM; 60min

Applications

Theaflavine-3,3’-digallate significantly inhibits Na+/K+-ATPase activity in a dose-dependent manner.
Cell experiment [2]:

Cell lines

HCT116 cells

Preparation Method

Cell viability was assessed using a variation of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenytetrazolium bromide (MTT) assay. HCT116 cells were seeded into 96-well plates (2×103 cells/well). After 24h of incubation at 37°C, the cells were treated with four conditions of Theaflavine-3,3’-digallate (TFDG). First, the cells were treated with different concentrations of TFDG (TFDG, 5–30μM) for 72h. Second, the cells were treated with different concentrations of pre-treated TFDG (O-TFDG) for 72h. The concentration of O-TFDG was expressed in TFDG equivalents. Third, the cells were treated by TFDG for only 3h, after which the media were replaced by fresh media for another 69h incubation (TFDG-3). Fourth, the cells were treated by O-TFDG for only 3h, after which the media were replaced by fresh media for another 69h of incubation (O-TFDG-3). After 72h, the number of viable cells compared with the control were detected using MTT assay. The treatment media were changed with 100μl of fresh media containing 0.5mg/ml of MTT and incubated for 1.5h. The media were replaced again by 100μl of DMSO. After gentle shaking, the optical density (OD) was measured at 570nm using a microplate reader.

Reaction Conditions

5-30μM; 3, 72h

Applications

The Theaflavine-3,3’-digallate pretreatment exerts growth inhibitory effects on HCT116 cells in a dose- and time-dependent manner.
Animal experiment [3]:

Animal models

BALB/c nude mice (NCI-N87/luc tumor xenograft models)

Preparation Method

NCI-N87/luc tumor xenograft models were established in athymic nude mice. Tumors were imaged by an in vivo Imaging System. To evaluate SHCBP1 knockdown involving in the gastric cancer sensitivity to trastuzumab, female BALB/c nude mice (6–8 weeks of age) received single subcutaneous flank injection of 1 × 106 Lenti-vector or Lenti-shRNA targeting NCI-N87/luc cells in a 1:1 PBS:Matrigel suspension. When tumor volumes reached 100mm3, trastuzumab was given at 10mg/kg intraperitoneally twice weekly. Tumors were measured by caliper three times per week. Animals were sacrificed and immunohistochemical staining was performed in the tumors after drug treatment for 21 days. To determine the synergistic effects of combining trastuzumab with Theaflavine-3,3'-digallate, NCI-N87/luc cells (1 × 106 cells per site) in suspension were mixed with equal volumes of Matrigel and injected subcutaneously into 6–8-week old female BALB/c nude mice. When tumor volumes reached 100mm3, preestablished NCI-N87 tumor xenografts were treated with vehicle, trastuzumab (intraperitoneal, 10mg/kg, 2×/wk × 3), Theaflavine-3,3'-digallate (subcutaneous, 2.5mg/kg or intraperitoneal, 50mg/kg, 1×/day × 21), or a combination of the agents. At the end of experiments, animals were sacrificed and subcutaneous tumors were harvested. Tumor proliferation was assessed by Ki-67 immunohistochemical staining.

Dosage form

50mg/kg/day; 21 days; i.p.

Applications

Theaflavine-3,3'-digallate combined with trastuzumab treatment significantly inhibited the tumor growth in xenograft mice carrying NCI-N87 tumor cells and induced a sharp regression of the tumors.

References:
[1] Qu F, Liu S, He C, et al. Comparison of the effects of green and black tea extracts on Na+/K+?ATPase activity in intestine of type 1 and type 2 diabetic mice[J]. Molecular nutrition & food research, 2019, 63(17): 1801039.
[2] Ding Y, Chen B, Gao Z, Suo H, Xiao H. Pre-treated theaflavin-3,3'-digallate has a higher inhibitory effect on the HCT116 cell line. Food Nutr Res. 2017 Nov 15;61(1):1400340.
[3] Shi W, Zhang G, Ma Z, et al. Hyperactivation of HER2-SHCBP1-PLK1 axis promotes tumor cell mitosis and impairs trastuzumab sensitivity to gastric cancer[J]. Nature Communications, 2021, 12(1): 2812.

Chemical Properties

CAS No.
33377-72-9
Chemical Name
(2S,3S)-2-(8-((2R,3R)-5,7-dihydroxy-3-((3,4,5-trihydroxybenzoyl)oxy)chroman-2-yl)-3,4,6-trihydroxy-5-oxo-5H-benzo[7]annulen-1-yl)-5,7-dihydroxychroman-3-yl 3,4,5-trihydroxybenzoate
SMILES
OC(C=C1O2)=CC(O)=C1C[C@](OC(C3=CC(O)=C(O)C(O)=C3)=O)([H])[C@@]2([H])C(C=C4O)=CC(C([C@@]5([H])[C@](OC(C6=CC(O)=C(O)C(O)=C6)=O)([H])CC7=C(O)C=C(O)C=C7O5)=CC(O)=C8O)=C8C4=O
Molecular Formula
C43H32O20
Molecular Weight
868.7
Solubility
Soluble in DMSO
Storage
Store at -20°C
General tips
Select a suitable solvent according to the product solubility data. Once prepared, aliquot the stock solution to avoid repeated freeze-thaw cycles.
Use stock solutions within 6 months when stored at -80°C or within 1 month when stored at -20°C.
To improve solubility, warm the tube to 37°C and sonicate it for an appropriate period.
Shipping Condition
Evaluation samples are shipped with blue ice. Other available sizes are shipped at room temperature or with blue ice upon request.

CalculatorsMolarity / Dilution / Molecular Weight / Unit Conversion / In Vivo Formulation / Solubility

g/mol

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