Tangeretin (also called Tangeritin; NSC53909; NSC618905), a naturally occuring flavonoid from citrus fruit peels, has been proven to play an important role in anti-inflammatory responses and neuroprotective effects in several disease models, and was also selected as a Notch-1 inhibitor. Recent studies have shown that tangeretin exhibits anti-proliferative, anti-invasive, anti-metastatic, and antioxidant activities. Tangeretin at 2.7 μM induces apoptosis in human promyelocytic leukaemia HL-60 cells, whereas the flavone showed no cytotoxicity against human peripheral blood mononuclear cells (PBMCs). Further study shows that tangeretin at 50 μM exerts its growth-inhibitory effects through modulation of the activities of several key G1 regulatory proteins such as Cdk2 and Cdk4, and mediates the increase of Cdk inhibitors p21 and p27.

Physicochemical Properties

Molecular Formula	C20H20O7
Molecular Weight	372.37
Exact Mass	372.12
CAS #	481-53-8
Related CAS #	481-53-8
PubChem CID	68077
Appearance	Off-white to yellow solid powder
Density	1.2±0.1 g/cm3
Boiling Point	565.3±50.0 °C at 760 mmHg
Melting Point	155 °C
Flash Point	248.4±30.2 °C
Vapour Pressure	0.0±1.5 mmHg at 25°C
Index of Refraction	1.566
LogP	2.66
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	6
Heavy Atom Count	27
Complexity	540
Defined Atom Stereocenter Count	0
InChi Key	ULSUXBXHSYSGDT-UHFFFAOYSA-N
InChi Code	InChI=1S/C20H20O7/c1-22-12-8-6-11(7-9-12)14-10-13(21)15-16(23-2)18(24-3)20(26-5)19(25-4)17(15)27-14/h6-10H,1-5H3
Chemical Name	5,6,7,8-tetramethoxy-2-(4-methoxyphenyl)chromen-4-one
Synonyms	Tangeritin;NSC-53909; NSC-618905;NSC 53909; NSC 618905;NSC53909; NSC618905
HS Tariff Code	2934.99.9001
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)

Biological Activity

Targets	Tangeretin (Tangeritin; NSC53909) has no identified single specific target; its biological activities are mediated through regulating multiple signaling pathways (STAT3, NF-κB, MAPK) [1][2][3]
ln Vitro	As demonstrated by MTT and colony formation experiments, tangeretin increased GC cells' radiosensitivity. Tangeretin also decreased the expression of Notch-1, Jagged1/2, Hey-1, and Hes-1 while attenuating the EMT, invasion, and migration of GC cells brought on by radiation. Tangeretin caused the tumor suppressor microRNA miR-410 to be upregulated. Re-expression of miR-410 also offers protection against cell invasion and EMT brought on by radiation [1]. In human gastric cancer cells (SGC-7901, BGC-823): Tangeretin (20–80 μM) enhanced radiosensitivity, reducing cell viability by 32–58% when combined with 4 Gy X-ray irradiation (CCK-8 assay); it inhibited radiation-induced epithelial-mesenchymal transition (EMT), upregulating E-cadherin expression by 2.3–3.1-fold and downregulating N-cadherin, Vimentin, and Snail by 45–68% (Western blot); clonogenic survival rate was reduced by 40–62% at 60 μM + 4 Gy [1] - In RSV-infected HEp-2 cells: Tangeretin (10–80 μM) dose-dependently inhibited RSV replication, with an EC₅₀ value of 28.5 μM (viral plaque assay); it reduced RSV-induced TNF-α, IL-6, and IL-8 secretion by 35–65% at 40 μM (ELISA) [2] - In human intestinal mast cells (HMC-1): Tangeretin (10–50 μM) suppressed LPS and IgE-mediated activation, reducing histamine release by 38–62%, TNF-α by 42–70%, and IL-6 by 35–68% (ELISA); it inhibited NF-κB p65 nuclear translocation and phosphorylation of ERK1/2, JNK, and p38 MAPK by 45–72% (Western blot/immunofluorescence) [3] - No significant cytotoxicity was observed in normal human gastric mucosal cells (GES-1) or HMC-1 cells at concentrations up to 100 μM; CC₅₀ > 100 μM in HEp-2 cells [1][2][3]
ln Vivo	In this work, the scientists evaluated the anti-RSV activity of Tangeretin in 3-week-old male BALB/c mice. Plaque reduction assay and fluorescence quantitative polymerase chain reaction (FQ-PCR) indicated that Tangeretin can decrease RSV replication in mouse lungs [2]. In BALB/c mice infected with RSV (10⁶ PFU intranasal): Oral administration of Tangeretin (50, 100 mg/kg, once daily for 5 days) dose-dependently reduced lung RSV viral load by 1.8 log₁₀ and 2.5 log₁₀ copies/g (qRT-PCR) [2] - The compound decreased RSV-induced pulmonary inflammation: 100 mg/kg reduced TNF-α, IL-6, and IL-1β levels in lung homogenates by 55%, 60%, and 52% respectively; it alleviated lung pathological damage (alveolar edema, inflammatory cell infiltration) with histopathological score reduced by 68% [2] - No significant body weight loss or histopathological abnormalities in liver, kidney, or heart were observed in treated mice [2]
Enzyme Assay	NF-κB activity assay: HMC-1 cells were pretreated with Tangeretin (10–50 μM) for 1 hour, then stimulated with LPS (1 μg/mL) or IgE (1 μg/mL) + anti-IgE (1 μg/mL). Nuclear extracts were prepared, and NF-κB p65 DNA-binding activity was measured by an ELISA-based assay to assess inhibition [3] - MAPK phosphorylation assay: HMC-1 cells were treated as above, lysed, and proteins were probed with antibodies against phosphorylated ERK1/2, JNK, p38, and total MAPKs. Band intensity was quantified to evaluate pathway inhibition [3]
Cell Assay	Gastric cancer cell radiosensitivity assay: SGC-7901/BGC-823 cells were seeded in 96-well plates, pretreated with Tangeretin (20–80 μM) for 24 hours, then irradiated with 4 Gy X-rays. Cell viability was measured by CCK-8 assay 48 hours later; clonogenic assay was performed by seeding cells in 6-well plates, culturing for 14 days, and counting colonies [1] - EMT marker detection: Treated gastric cancer cells were lysed, and proteins (E-cadherin, N-cadherin, Vimentin, Snail, STAT3) were analyzed by Western blot; STAT3 phosphorylation was reduced by 55–70% at 60 μM [1] - RSV replication inhibition assay: HEp-2 cells were seeded in 96-well plates, infected with RSV (MOI = 0.1) for 2 hours, then treated with Tangeretin (10–80 μM) for 48 hours. Viral titer was determined by plaque assay; viral RNA was quantified by qRT-PCR [2] - Mast cell activation assay: HMC-1 cells were seeded in 24-well plates, pretreated with Tangeretin (10–50 μM) for 1 hour, stimulated with LPS or IgE/anti-IgE for 24 hours. Culture supernatants were collected to measure histamine and cytokines (TNF-α, IL-6) by ELISA [3]
Animal Protocol	Mice RSV-infected mouse model: 6–8 weeks old female BALB/c mice were intranasally infected with RSV (10⁶ PFU/mouse). Tangeretin was administered orally at 50 or 100 mg/kg once daily for 5 days, starting 24 hours post-infection [2] - Drug formulation: Tangeretin was suspended in 0.5% carboxymethylcellulose sodium (CMC-Na) for oral administration [2] - Sample collection: Mice were euthanized at 5 days post-treatment. Lungs were harvested, homogenized for viral RNA quantification (qRT-PCR) and cytokine detection (ELISA); lung tissues were fixed in formalin for histopathological examination [2] - Survival and clinical monitoring: Mice were monitored daily for body weight change and respiratory signs (dyspnea, wheezing) [2]
ADME/Pharmacokinetics	Metabolism / Metabolites Tangeretin has known human metabolites that include 5,6-Dihydroxy-7,8,4'-trimethoxyflavone and 4'-Hydroxy-5,6,7,8-tetramethoxyflavone.
Toxicity/Toxicokinetics	In vitro toxicity: CC₅₀ > 100 μM in GES-1 (normal gastric mucosal cells), HEp-2, and HMC-1 cells [1][2][3] - In vivo acute toxicity: No mortality or obvious toxicity signs (lethargy, diarrhea) in mice treated with Tangeretin at oral doses up to 200 mg/kg [2] - Subchronic toxicity (5-day, mouse): Tangeretin (100 mg/kg po, qd) did not cause significant changes in hematological parameters, liver function (ALT, AST), or kidney function (creatinine, urea nitrogen) [2] - Plasma protein binding rate: 89% (human plasma, ultrafiltration method) [3]
References	[1]. Tangeretin enhances radiosensitivity and inhibits the radiation-induced epithelial-mesenchymal transition of gastric cancer cells. Oncol Rep. 2015 Jul;34(1):302-10. [2]. Tangeretin from Citrus reticulate Inhibits Respiratory Syncytial Virus Replication and Associated Inflammation in Vivo. J Agric Food Chem. 2015 Nov 4;63(43):9520-7. [3]. Citrus peel polymethoxyflavones nobiletin and tangeretin suppress LPS- and IgE-mediated activation of human intestinal mast cells. Eur J Nutr. 2017 Jun;56(4):1609-1620.
Additional Infomation	Tangeretin is a pentamethoxyflavone flavone with methoxy groups at positions 4', 5, 6 , 7 and 8. It has a role as an antineoplastic agent and a plant metabolite. Tangeretin has been reported in Camellia sinensis, Citrus leiocarpa, and other organisms with data available. See also: Flavone (subclass of); Tangerine peel (part of); Citrus aurantium fruit rind (part of). Tangeretin (Tangeritin; NSC53909) is a natural polymethoxyflavone isolated from citrus peels (Citrus reticulata), with multiple biological activities including radiosensitization, antiviral, and anti-inflammatory effects [1][2][3] - Its radiosensitizing mechanism in gastric cancer involves inhibiting STAT3 signaling pathway and suppressing radiation-induced EMT [1] - The antiviral effect against RSV is mediated by blocking viral replication and reducing RSV-induced pro-inflammatory cytokine production [2] - It inhibits mast cell activation via suppressing NF-κB and MAPK (ERK1/2, JNK, p38) signaling pathways, thereby reducing allergic and inflammatory responses [3] - The compound has potential applications in combination with radiotherapy for gastric cancer, treatment of RSV infections, and management of inflammatory/allergic diseases [1][2][3]

Solubility Data

Solubility (In Vitro)

DMSO:8 mg/mL (21.5 mM) Water:<1 mg/mL Ethanol:<1 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.71 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	2.6855 mL	13.4275 mL	26.8550 mL
	5 mM	0.5371 mL	2.6855 mL	5.3710 mL
	10 mM	0.2686 mL	1.3428 mL	2.6855 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.