 Chemical Structure.png)
Physicochemical Properties
| Molecular Formula | C25H42O6 |
| Molecular Weight | 438.60 |
| Exact Mass | 438.298 |
| Elemental Analysis | C, 68.46; H, 9.65; O, 21.89 |
| CAS # | 142861-00-5 |
| PubChem CID | 6438496 |
| Appearance | White to yellow solid powder |
| Density | 1.056g/cm3 |
| Boiling Point | 567.9ºC at 760 mmHg |
| Flash Point | 181.9ºC |
| Vapour Pressure | 2.92E-15mmHg at 25°C |
| Index of Refraction | 1.497 |
| LogP | 4.362 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 11 |
| Heavy Atom Count | 31 |
| Complexity | 658 |
| Defined Atom Stereocenter Count | 9 |
| SMILES | O1[C@]([H])([C@]([H])(C([H])([H])[H])[C@]([H])([C@@]([H])(C([H])([H])[H])O[H])OC([H])([H])[H])[C@@]1(C([H])([H])[H])C([H])([H])[C@@]([H])(/C(/[H])=C(\[H])/C(/[H])=C(\C([H])([H])[H])/[C@]1([H])[C@@]([H])(C([H])([H])[H])C([H])([H])C([H])([H])[C@]([H])(C([H])([H])C(=O)O[H])O1)C([H])([H])[H] |
| InChi Key | ISZXEMUWHQLLTC-LSIVYLFASA-N |
| InChi Code | InChI=1S/C25H42O6/c1-15(14-25(6)24(31-25)18(4)23(29-7)19(5)26)9-8-10-16(2)22-17(3)11-12-20(30-22)13-21(27)28/h8-10,15,17-20,22-24,26H,11-14H2,1-7H3,(H,27,28)/b9-8+,16-10+/t15-,17+,18-,19-,20-,22-,23-,24-,25-/m1/s1 |
| Chemical Name | 2-[(2R,5S,6S)-6-[(2E,4E,6S)-7-[(2R,3R)-3-[(2R,3R,4R)-4-hydroxy-3-methoxypentan-2-yl]-2-methyloxiran-2-yl]-6-methylhepta-2,4-dien-2-yl]-5-methyloxan-2-yl]acetic acid |
| Synonyms | GEX1A; Tan1609; Tan-1609; Herboxidiene; 142861-00-5; QSB7EM5EUD; 2-[(2R,5S,6S)-6-[(2E,4E,6S)-7-[(2R,3R)-3-[(2R,3R,4R)-4-hydroxy-3-methoxypentan-2-yl]-2-methyloxiran-2-yl]-6-methylhepta-2,4-dien-2-yl]-5-methyloxan-2-yl]acetic acid; TAN 1609; GEX1A compound; (+)-Herboxidiene; UNII-QSB7EM5EUD; Tan 1609; Herboxidiene |
| 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: (1). This product requires protection from light (avoid light exposure) during transportation and storage.(2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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 | Pre-mRNA splicing |
| ln Vitro | In a human normal fibroblast cell line, WI-38, herboxidiene (24 hours) produces both G1 and G2/M arrest with an IC50 of 7.6 nM[3]. With IC50s of 3.7, 21, and 51 nM, respectively, herboxidiene demonstrates cytotoxicity against A431, A549, and DLD-1 cells[3]. |
| ln Vivo | The anticancer efficacy of herboxidiene (GEX1A) (1 mg/kg; ip; once) is noteworthy[3]. |
| Animal Protocol |
Animal/Disease Models: balb/c (Bagg ALBino) mouse: (bearing SVT2 murine fibrosarcoma)[3] Doses: 1 mg/kg Route of Administration: Ip; once Experimental Results: demonstrated significant antitumor activity on day 4. |
| References |
[1]. Herboxidiene biosynthesis, production, and structural modifications: prospect for hybrids with related polyketide. Appl Microbiol Biotechnol. 2015;99(20):8351‐8362. [2]. GEX1 compounds, novel antitumor antibiotics related to herboxidiene, produced by Streptomyces sp. I. Taxonomy, production, isolation, physicochemical properties and biological activities. J Antibiot (Tokyo). 2002;55(10):855‐862. [3]. Herboxidiene, a new herbicidal substance from Streptomyces chromofuscus A7847. Taxonomy, fermentation, isolation, physico-chemical and biological properties. J Antibiot (Tokyo). 1992;45(6):914‐921. |
| Additional Infomation |
Herboxidiene has been reported in Streptomyces chromofuscus with data available. See also: Gex1Q1 (annotation moved to). Herboxidiene is a polyketide with a diverse range of activities, including herbicidal, anti-cholesterol, and pre-mRNA splicing inhibitory effects. Thus, production of the compound on the industrial scale is in high demand, and various rational metabolic engineering approaches have been employed to enhance the yield. Directing the precursors and cofactors pool toward the production of polyketide compounds provides a rationale for developing a good host for polyketide production. Due to multiple promising biological activities, the production of a number of herboxidiene derivatives has been attempted in recent years in a search for the key to improve its potency and to introduce new activities. Structural diversification through combinatorial biosynthesis was attempted, utilizing the heterologous expression of substrate-flexible glucosyltransferase (GT) and cytochrome P450 in Streptomyces chromofuscus to generate structurally and functionally diverse derivatives of herboxidiene. The successful attempt confirmed that the strain was amenable to heterologous expression of foreign polyketide synthase (PKS) or post-PKS modification genes, providing the foundation for generating novel or hybrid polyketides.[1] Six structurally related antitumor antibiotics named GEX1 compounds were isolated from a culture broth of Streptomyces sp. GEX1A was identified as a known herbicide, herboxidiene, structurally interested by the tetrahydropyran moiety and the side chain including a conjugated diene. GEX1Q1 to approximately Q5 were determined as novel compounds related to herboxidiene. All GEX1 compounds showed cytotoxicity with IC50 values of 0.0037 to approximately 0.99 microM against human tumor cell lines in vitro, but were not active against both gram-positive and -negative bacteria. Though GEX1A/herboxidiene exhibited antitumor activity in murine tumor-planted mouse models, both GEX1Q3 and GEX1Q5 did not.[2] Screening of microbial fermentation broths for herbicidal activity led to the discovery of a novel polyketide, herboxidiene, from an actinomycete identified as a member of the Streptomyces chromofuscus cluster. A 14- to 20-fold increase in fermentation production of herboxidiene was achieved as a result of media optimization. Herboxidiene was purified using successive reverse phase C18 steps and Sephadex LH-20 chromatography. Its molecular formula, C25H42O6, was determined by HRFAB-MS. Herboxidiene demonstrated exceptionally potent, selective, herbicidal activity against a variety of weed species and was inactive against wheat, even at rates as high as 5.6 kg/hectare.[3] |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2800 mL | 11.3999 mL | 22.7998 mL | |
| 5 mM | 0.4560 mL | 2.2800 mL | 4.5600 mL | |
| 10 mM | 0.2280 mL | 1.1400 mL | 2.2800 mL |