Icaritin (Anhydroicaritin) is a naturally occurring flavonoid isolated frp, Epimedium brevicornuMaxim. It is a traditional Chinese medicine acting as a modulator of estrogen receptor α36. Also inhibits the proliferation of K562 cells (IC50 of 8 µM) and primary CML cells (IC50 of 13.4 µM for CML-CP and 18 µM for CML-BC). Icaritin regulates MAPK/ERK/JNK and JAK2/STAT3 /AKT signalings, also enhances osteogenesis
Physicochemical Properties
| Molecular Formula | C21H20O6 |
| Molecular Weight | 368.385 |
| Exact Mass | 368.125 |
| CAS # | 118525-40-9 |
| PubChem CID | 5318980 |
| Appearance | Light yellow to yellow solid powder |
| Density | 1.4±0.1 g/cm3 |
| Boiling Point | 582.0±50.0 °C at 760 mmHg |
| Melting Point | 239ºC |
| Flash Point | 206.7±23.6 °C |
| Vapour Pressure | 0.0±1.7 mmHg at 25°C |
| Index of Refraction | 1.657 |
| LogP | 4.84 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 27 |
| Complexity | 612 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | TUUXBSASAQJECY-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C21H20O6/c1-11(2)4-9-14-15(22)10-16(23)17-18(24)19(25)20(27-21(14)17)12-5-7-13(26-3)8-6-12/h4-8,10,22-23,25H,9H2,1-3H3 |
| Chemical Name | 3,5,7-trihydroxy-2-(4-methoxyphenyl)-8-(3-methylbut-2-enyl)chromen-4-one |
| Synonyms | IcaritinAnhydroicaritin |
| 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
| ln Vitro | Treatment with isaurin (4-64 μM; 48 hours; K562, imatinib-intervention cells, and primary CML cells) suppresses the proliferation of these patient types [1]. Icariin (32 μM; K562 cells) therapy induced in K562 or primary cells in a concentration-dependent manner, increasing sub-G1 phase in K562 cells 0-64 μM; 48 hours [1]. The Bcl-cell population in K562 was likewise markedly reduced by icaridin treatment [1]. |
| ln Vivo | In a mouse leukemia model, icarcitin (4–8 mg/kg; intraperitoneal injection; daily; for 10 weeks; female NOD-SCID nude mice) treatment could increase the longevity of NOD-SCID nude mice injected with K562 cells without suppressing bone marrow[1]. |
| Cell Assay |
Cell Proliferation Assay[1] Cell Types: K562, 2 expresses protein and upregulates Bax protein expression in a dose-dependent manner, accompanied by the cleavage activation of caspase-3 or caspase-9, and the expression of Apaf-1[1]. Imatinib-resistant cells and primary CML cells Tested Concentrations: 4 µM, 8 µM, 16 µM, 32 µM and 64 µM Incubation Duration: 48 hrs (hours) Experimental Results: Inhibition of cell proliferation. Apoptosis analysis[1] Cell Types: K562 or primary cells Tested Concentrations: 0 µM, 4 µM, 8 µM, 16 µM, 32 µM and 64 µM Incubation Duration: 48 hrs (hours) Experimental Results: Induction of apoptosis in K562 or primary cells. Cell cycle analysis[1] Cell Types: K562 Cell Tested Concentrations: 32 µM Incubation Duration: Experimental Results: Increased number of cells in sub-G1 phase. Western Blot Analysis[1] Cell Types: K562 Cell Tested Concentrations: 0 µM, 4 µM, 8 µM, 16 µM, 32 µM and 64 µM Incubation Duration: 48 hrs (hours) Experimental Results: Inhibits MAPK/ERK/JNK downstream signaling and attenuates Jak2/ Stat3 /Akt expression. |
| Animal Protocol |
Animal/Disease Models: Female NOD-SCID nude mice (6-8 weeks old) K562 cells [1] Doses: 4 mg/kg and 8 mg/kg Route of Administration: intraperitoneal (ip) injection; bone marrow [1]. Routine; 10 consecutive weeks Experimental Results: It can extend the lifespan of NOD-SCID nude mice inoculated with K562 cells without suppressing bone marrow. |
| References |
[1]. Icaritin shows potent anti-leukemia activity on chronic myeloid leukemia in vitro and in vivo by regulating MAPK/ERK/JNK and JAK2/STAT3 /AKT signalings. PLoS One. 2011;6(8):e23720. [2]. Icaritin, an exogenous phytomolecule, enhances osteogenesis but not angiogenesis--an in vitro efficacy study. PLoS One. 2012;7(8):e41264. [3]. An anticancer agent icaritin induces sustained activation of the extracellular signal-regulated kinase (ERK) pathway and inhibits growth of breast cancer cells. Eur J Pharmacol. 2011 May 11;658(2-3):114-22. |
| Additional Infomation |
Icaritin is a member of flavones. Icaritin has been used in trials studying the treatment of Solid Tumors, Metastatic Breast Cancer, and Hepatocellular Carcinoma (HCC). Icaritin has been reported in Epimedium acuminatum, Epimedium diphyllum, and other organisms with data available. |
Solubility Data
| Solubility (In Vitro) |
DMSO : ~15.62 mg/mL (~42.40 mM) H2O : ~1.2 mg/mL (~3.26 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: 10 mg/mL (27.15 mM) in 15% Cremophor EL + 85% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1.56 mg/mL (4.23 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 15.6 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 3: 1.51 mg/mL (4.10 mM) in 50% PEG300 50% 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7145 mL | 13.5726 mL | 27.1451 mL | |
| 5 mM | 0.5429 mL | 2.7145 mL | 5.4290 mL | |
| 10 mM | 0.2715 mL | 1.3573 mL | 2.7145 mL |