Gambogenic Acid, a naturally occuring ingredient dound in gamboge, is a potent inhibitor of the fibroblast growth factor receptor (FGFR) signaling pathway in erlotinib-resistant non-small-cell lung cancer (NSCLC). It can inhibit the growth of xenografts derived from patients and exhibit anticancer properties. Gambogenic acid specifically and covalently binds to Cys668 within the EZH2-SET domain, causing EZH2 ubiquitination, thereby acting as an effective inhibitor of EZH2.
Physicochemical Properties
| Molecular Formula | C38H46O8 |
| Molecular Weight | 630.7671 |
| Exact Mass | 630.319 |
| Elemental Analysis | C, 72.36; H, 7.35; O, 20.29 |
| CAS # | 173932-75-7 |
| Related CAS # | 173932-75-7 |
| PubChem CID | 10794070 |
| Appearance | Light yellow to yellow solid powder |
| Density | 1.3±0.1 g/cm3 |
| Boiling Point | 818.6±65.0 °C at 760 mmHg |
| Flash Point | 253.0±27.8 °C |
| Vapour Pressure | 0.0±3.1 mmHg at 25°C |
| Index of Refraction | 1.619 |
| LogP | 9.42 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 8 |
| Rotatable Bond Count | 10 |
| Heavy Atom Count | 46 |
| Complexity | 1440 |
| Defined Atom Stereocenter Count | 4 |
| SMILES | O1C(C([H])([H])[H])(C([H])([H])[H])C2([H])C([H])([H])[C@@]3([H])C([H])=C4C(C5=C(C(C([H])([H])/C(/[H])=C(\C([H])([H])[H])/C([H])([H])C([H])([H])/C(/[H])=C(\C([H])([H])[H])/C([H])([H])[H])=C(C(C([H])([H])/C(/[H])=C(\C([H])([H])[H])/C([H])([H])[H])=C5O[C@@]24C1(C([H])([H])/C(/[H])=C(\C(=O)O[H])/C([H])([H])[H])C3=O)O[H])O[H])=O |
| InChi Key | RCWNBHCZYXWDOV-VSFMGBBVSA-N |
| InChi Code | InChI=1S/C38H46O8/c1-20(2)10-9-11-22(5)13-15-25-30(39)26(14-12-21(3)4)33-29(31(25)40)32(41)27-18-24-19-28-36(7,8)46-37(34(24)42,38(27,28)45-33)17-16-23(6)35(43)44/h10,12-13,16,18,24,28,39-40H,9,11,14-15,17,19H2,1-8H3,(H,43,44)/b22-13+,23-16-/t24-,28+,37+,38-/m1/s1 |
| Chemical Name | (Z)-4-[(1S,2S,13S,15R)-7-[(2E)-3,7-dimethylocta-2,6-dienyl]-6,8-dihydroxy-17,17-dimethyl-5-(3-methylbut-2-enyl)-10,14-dioxo-3,16-dioxapentacyclo[11.4.1.02,11.02,15.04,9]octadeca-4,6,8,11-tetraen-15-yl]-2-methylbut-2-enoic acid |
| Synonyms | GNA; Gambogenic Acid |
| 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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 | FGFR; EZH2 |
| ln Vitro | Gambogenic acid is a novel agent that specifically and covalently binds to Cys668 within the EZH2‐SET domain, causing EZH2 degradation through ubiquitination at the COOH terminus of the Hsp70-interacting protein (CHIP). Gambogenic acid effectively reactivates polycomb repressor complex 2 (PRC2)-silenced tumor suppressor genes and significantly suppresses H3K27Me3. In an EZH2-dependent manner, gambogenic acid significantly suppresses the growth of tumors.[1] |
| ln Vivo | Gambogenic acid derivative GNA002 dramatically lowers H3K27Me3 levels in tumor tissues and the volumes of tumors derived from Cal-27 in xenograft mice. |
| Cell Assay | GNA002 or 2 μM GNA is applied to cancer cells for a full day. Subsequently, the cells are collected and mixed again with 500 μl of binding buffer. Different cell dyes are added to the 100 μl of cell suspension and incubated. Fluorescence-activated cell sorting is used to analyze the stained cells using a flow cytometry apparatus. |
| References |
[1]. EMBO J . 2017 May 2;36(9):1243-1260. [2]. Cell Death Dis . 2018 Feb 15;9(3):262. |
| Additional Infomation | Gambogenic Acid has been reported in Garcinia hanburyi with data available. |
Solubility Data
| Solubility (In Vitro) | DMSO: ~100 mg/mL (~158.5 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 4 mg/mL (6.34 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 40.0 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5854 mL | 7.9268 mL | 15.8536 mL | |
| 5 mM | 0.3171 mL | 1.5854 mL | 3.1707 mL | |
| 10 mM | 0.1585 mL | 0.7927 mL | 1.5854 mL |