 Chemical Structure.png)
Physicochemical Properties
| Molecular Formula | C10H12O5 |
| Molecular Weight | 212.20 |
| Exact Mass | 212.068 |
| CAS # | 88805-35-0 |
| Related CAS # | Prohexadione calcium;127277-53-6 |
| PubChem CID | 184900 |
| Appearance |
Fine white powder Pale yellow brown colored fine powder |
| Density | 1.33 g/cm3 |
| Boiling Point | 454.9ºC at 760 mmHg |
| Melting Point |
>360 °C Yellow powder with sweet smell. Melting point >360 °C. Hardly soluble in organic solvents. /Technical/ |
| Flash Point | 243.1ºC |
| Index of Refraction | 1.512 |
| LogP | 0.214 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 3 |
| Heavy Atom Count | 15 |
| Complexity | 313 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | O=C1C(C(=O)CC)C(=O)CC(C(O)=O)C1 |
| InChi Key | BUCOQPHDYUOJSI-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C10H12O5/c1-2-6(11)9-7(12)3-5(10(14)15)4-8(9)13/h5,9H,2-4H2,1H3,(H,14,15) |
| Chemical Name | 3,5-dioxo-4-propanoylcyclohexane-1-carboxylic 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 |
| 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 | Gibberellin biosynthesis[1] |
| ln Vitro | The activity of JMJD2A demethylase is inhibited by prohexadione (1 mM)[2]. Mouse neurospheres are induced to differentiate into neurons by prohexadione (1-2 mM)[2]. In soybean seedlings, prohexadione (100 mg/L) sprayed on the leaves reduces saline-alkali stress[3]. In potted apple trees, prohexadione increases structural resistance against fire blight infection[4]. |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion In a metabolism study in rats, prohexadione calcium was rapidly absorbed with highest tissue/carcass concentrations obtained within 30 minutes; however, absorption became saturated at the highest dose. The test material did not accumulate in the tissues. For low dose animals, renal excretion was the primary route of elimination. At the high dose, fecal excretion became the primary route of elimination. The primary excreta (both urine and feces) metabolite was identified as the free acid. Metabolism / Metabolites Male and female Fisher 344 rats were dosed by gavage with 50 or 500 mg/kg of [14C]-BX-112 (radiolabel at the 3 or 5 position on the cyclohexene ring)(lot no. CP-1107, radiochemical purity: 98.9%, specific activity: 97.8 mCi/mg). In Groups B (50 mg/kg) and D (500 mg/kg) (the mass balance studies), urine, feces and cage wash samples were collected up to 7 days from 5 animals/sex/group. In Group C1, 5 animals/sex were pretreated for 14 days with unlabelled BX-112 technical (purity: 93.8%), followed by 50 mg/kg of the radiolabelled material. Urine, feces and cage wash samples were collected up to 7 days after the final dose. Samples collected between 0 and 48 hours after dosing were analyzed to determine specific metabolites. In addition, radiolabelled material was extracted from liver and kidney tissue of one male each treated with either 50 mg/kg (Group B3) and 500 mg/kg (Group D3) and euthanized at 0.5 hours after dosing. The test material was largely excreted in the urine and the feces as the free acid (50 mg/kg: 38.3 to 39.1%, 500 mg/kg: 60.9 to 68.0%, and 50 mg/kg, repeated dose: 44.2 to 53.7% of the adminstered dose). An additional compound isolated in the urine was tentatively identified as an ester glucuronide of BX-112. The total conjugated fraction of the test material constituted 20.4 and 21.7% in the 50 mg/kg group, 7.3 and 3.7% in the 500 mg/kg group and 23.2 and 17.7% of the administered dose in the 50 mg/kg, repeated dosing group for the males and females, respectively. The only other identified metabolite was recovered from the organic phase of the feces extraction. This material was the despropionyl free acid of BX-112. It constituted no more than 2.3% of the administered dose in any of the groups examined. In the liver and the kidney, the predominant material recovered at both of the dosing levels was the free acid of the BX-112 (liver: 81.2 and 93.1% of the recovered radiolabel in the 50 and 500 mg/kg, respectively; kidney: 70.1 and 91.8% of the recovered label in the 50 and 500 mg/kg groups, respectively); in the addendum, two of the previously unknown compounds were noted to be methyl esters of the test material and the despropionyl metabolite and were considered to be artifacts; further information was provided regarding the isolation of radiolabelled compounds in the feces; the isolated compound was largely the free acid of the parent compound as had been originally reported; in addition, use of a C18 HPLC column rather than the C8 one resulted in a different ratio of the parent compound and the conjugate noted in the original analysis; further analysis of this "conjugate" by FAB-MS and Atmospheric Pressure Electrospray HPLC/MS did not result in a definitive identification of the compound. |
| Toxicity/Toxicokinetics |
Toxicity Data LC50 (rat) > 4,210 mg/m3/4h Non-Human Toxicity Values LD50 Rat oral >5000 mg/kg LD50 Rat dermal >2000 mg/kg LD50 Mouse oral >5000 mg/kg LC50 Rat inhalation >4.21 mg/L air/4 hr (whole body) |
| References |
[1]. Effect of a plant growth regulator prohexadione-calcium on insect pests of apple and pear. J Econ Entomol. 2005 Apr;98(2):423-31. [2]. Prohexadione, a plant growth regulator, inhibits histone lysine demethylases and modulates epigenetics. Toxicol Rep. 2014 Nov 4;1:1152-1161. [3]. Prohexadione-calcium alleviates saline-alkali stress in soybean seedlings by improving the photosynthesis and up-regulating antioxidant defense. Ecotoxicol Environ Saf. 2021 Sep 1;220:112369. [4]. Evidence that prohexadione-calcium induces structural resistance to fire blight infection. Phytopathology. 2009 May;99(5):591-6. |
| Additional Infomation | Prohexadione is a 4-oxo monocarboxylic acid that is cyclohexanecarboxylic acid which is substituted by oxo groups at positions 3 and 5, and by a propanoyl group at position 4. A plant growth regulator, it is used (commonly as the corresponding calcium salt, known as prohexadione-calcium) as an anti-lodging agent in small-grain cereals. It has a role as an agrochemical, a plant growth regulator and a gibberellin biosynthesis inhibitor. It is a 4-oxo monocarboxylic acid and a beta-triketone. It is a conjugate acid of a prohexadione(2-). |
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 | 4.7125 mL | 23.5627 mL | 47.1254 mL | |
| 5 mM | 0.9425 mL | 4.7125 mL | 9.4251 mL | |
| 10 mM | 0.4713 mL | 2.3563 mL | 4.7125 mL |