667463-85-6
667463-85-6 structure
- Name: BIO-acetoxime
- Chemical Name: [[2-(6-bromo-2-oxo-1H-indol-3-ylidene)indol-3-yl]amino] acetate
- CAS Number: 667463-85-6
- Molecular Formula: C18H12BrN3O3
- Molecular Weight: 398.210
- Catalog: Signaling Pathways PI3K/Akt/mTOR GSK-3
- Create Date: 2018-06-25 07:58:34
- Modify Date: 2024-01-02 23:08:53
-
BIO-acetoxime (BIA) is a potent and selective GSK-3 inhibitor, with IC50s of both 10 nM for GSK-3α/β. BIO-acetoxime has anticonvulsant and anti-infection activity.
| Name | [[2-(6-bromo-2-oxo-1H-indol-3-ylidene)indol-3-yl]amino] acetate |
|---|---|
| Synonyms |
2H-Indol-2-one, 3-[(3E)-3-[(acetyloxy)imino]-1,3-dihydro-2H-indol-2-ylidene]-6-bromo-1,3-dihydro-, (3Z)-
2H-Indol-2-one, 3-[(3E)-3-[(acetyloxy)imino]-1,3-dihydro-2H-indol-2-ylidene]-6-bromo-1,3-dihydro-, (3E)- (3Z)-3-[(3E)-3-(Acetoxyimino)-1,3-dihydro-2H-indol-2-ylidene]-6-bromo-1,3-dihydro-2H-indol-2-one (3E)-3-[(3E)-3-(Acetoxyimino)-1,3-dihydro-2H-indol-2-ylidene]-6-bromo-1,3-dihydro-2H-indol-2-one in1315 (3Z)-3-{(3E)-3-[(acetyloxy)imino]-1,3-dihydro-2H-indol-2-ylidene}-6-bromo-1,3-dihydro-2H-indol-2-one 6-Bromoindirubin-3'-acetoxime BIO-acetoxime GSK-3 Inhibitor X |
| Description | BIO-acetoxime (BIA) is a potent and selective GSK-3 inhibitor, with IC50s of both 10 nM for GSK-3α/β. BIO-acetoxime has anticonvulsant and anti-infection activity. |
|---|---|
| Related Catalog | |
| Target |
GSK-3α:10 nM (IC50) GSK-3β:10 nM (IC50) CDK5/p35:2.4 μM (IC50) CDK2/cyclin A:4.3 μM (IC50) CDK1/cyclin B:63 μM (IC50) |
| In Vitro | BIO-acetoxime (BIA; Compound 13) is a potent and selective GSK-3α/β inhibitor, with IC50s of both 10 nM. BIO-acetoxime (BIA) shows weak effect on CDK5/p35 (IC50, 2.4 μM), CDK2/cyclin A (IC50, 4.3 μM), and CDK1/cyclin B (IC50, 63 μM)[1]. BIO-acetoxime (BIA) (5 μM and 10 μM) increases the viability of HSV-1-infected cells but shows little effect on morphology and viability of mockin-fected cells. Moreover, BIO-acetoxime (BIA) (0.625, 1.25, 2.5, 5, and 10 μM) significantly reduces the release of HSV-1 particles in OC3 cells, with an EC50 of 0.68 ± 0.28 μM. BIO-acetoxime (BIA) inhibits the expression of HSV-1 genes, and may not affect the nuclear targeting of HSV-1 capsids. In addition, delayed addition of BIO-acetoxime (BIA) also inhibits HSV-1 infection[2]. |
| In Vivo | BIO-acetoxime (BIA) shows anticonvulsant effects in the focal pilocarpine rat model at 0.5 mg/kg, and in 6-Hz fully kindled FVB/N mice at 0.5, 2.5, and 5 mg/kg via i.p. administration[3]. |
| Cell Assay | OC3 cells are seeded in 3.5- and 6-cm diameter dishes for western blot analysis and RNA isolation, respectively. Cells are mock treated or exposed to HSV-1 at a multiplicity of infection (m.o.i.) of 5 unless otherwise specified. The glycogen synthase kinase-3 (GSK-3) inhibitor BIO-acetoxime (BIA), is first dissolved in DMSO to make a stock solution. Medium containing DMSO serves as a solvent control. Cells are pretreated with medium only, medium containing 0.1 % DMSO or BIO-acetoxime (BIA) for 45 min prior to mock or HSV-1 infection. BIO-acetoxime (BIA) is also present throughout the infection period. To examine the direct effect on viruses, HSV-1 is treated directly with medium containing 5 μM BIO-acetoxime (BIA) for 1 h at room temperature. Cell morphology is observed with an inverted microscope[2]. |
| Animal Admin | Mice[3] Male FVB/N mice are used to test the anticonvulsant effects of BIO-acetoxime in fully kindled mice. To achieve the fully kindled state, mice are stimulated at a fixed subconvulsive threshold current twice daily, except the weekends, with a 4 h minimum interval between stimulations. Kindled mice are then stimulated for only 2 days a week, twice daily to maintain the fully kindled state. Meanwhile nonkindled mice are kept at the original stimulation scheme for maximum 1-2 more weeks. The anticonvulsant effect of BIO-acetoxime (BIA) is investigated in the “epileptic” fully kindled mice by stimulating these animals on Monday morning. On Monday afternoon, the animals are intraperitoneally (i.p.) injected with vehicle, 30 min prior to stimulation. On Tuesday morning, mice are again stimulated. On Tuesday afternoon, mice are injected i.p. with BIO-acetoxime (BIA) and are stimulated 30 min later. Seizure severity is assessed using Racine’s scale. The pretreatment scores are compared with the post-treatment scores, obtained after the treatment on Tuesday. To confirm any observed effects, the experiment is repeated, respecting 1 week of washout. During this washout week, all mice are stimulated for 2 days (twice daily) to maintain the kindled state. Compound testing during a longer period has not been validated so far. This means that only one dose of BIO-acetoxime can be tested in one batch of kindled mice[3]. |
| References |
| Density | 1.7±0.1 g/cm3 |
|---|---|
| Molecular Formula | C18H12BrN3O3 |
| Molecular Weight | 398.210 |
| Exact Mass | 397.006195 |
| PSA | 83.28000 |
| LogP | 2.37 |
| Index of Refraction | 1.741 |
| Storage condition | -20℃ |
|
SECTION 1: Identification of the substance/mixture and of the company/undertaking Product identifiers Product name: BIO-Acetoxime REACH No.: A registration number is not available for this substance as the substance or its uses are exempted from registration, the annual tonnage does not require a registration or the registration is envisaged for a later registration deadline.
CAS-No.: 667463-85-6 Relevant identified uses of the substance or mixture and uses advised against Identified uses: Laboratory chemicals, Manufacture of substances SECTION 2: Hazards identification Classification of the substance or mixture Classification according to Regulation (EC) No 1272/2008 Acute toxicity, Oral (Category 4), H302 Acute aquatic toxicity (Category 1), H400 Chronic aquatic toxicity (Category 1), H410 For the full text of the H-Statements mentioned in this Section, see Section 16. Classification according to EU Directives 67/548/EEC or 1999/45/EC N, Xn Dangerous for theR22, R50/53 environment, Harmful For the full text of the R-phrases mentioned in this Section, see Section 16. Label elements Labelling according Regulation (EC) No 1272/2008 Pictogram Signal wordWarning Hazard statement(s) H302Harmful if swallowed. H410Very toxic to aquatic life with long lasting effects. Precautionary statement(s) P273Avoid release to the environment. P501Dispose of contents/ container to an approved waste disposal plant. Supplemental Hazardnone Statements Other hazards - none SECTION 3: Composition/information on ingredients Substances Synonyms: BIA (2'Z,3'E)-6-Bromoindirubin-3'-acetoxime 6-Bromoindirubin-3'-acetoxime 6-Bromoindirubin acetoxime (3Z)-3-[(3E)-3-[(Acetyloxy)imino]-1,3-dihydro-2H-indol-2-ylidene]-6- bromo-1,3-dihydro-2H-Indol-2-one Formula: C18H12BrN3O3 Molecular Weight: 398,21 g/mol CAS-No.: 667463-85-6 Hazardous ingredients according to Regulation (EC) No 1272/2008 ComponentClassificationConcentration (2'Z,3'E)-6-Bromoindirubin-3'-acetoxime Acute Tox. 4; Aquatic Acute 1; - Aquatic Chronic 1; H302, H410 For the full text of the H-Statements and R-Phrases mentioned in this Section, see Section 16 SECTION 4: First aid measures Description of first aid measures General advice Consult a physician. Show this safety data sheet to the doctor in attendance. If inhaled If breathed in, move person into fresh air. If not breathing, give artificial respiration. Consult a physician. In case of skin contact Wash off with soap and plenty of water. Consult a physician. In case of eye contact Flush eyes with water as a precaution. If swallowed Never give anything by mouth to an unconscious person. Rinse mouth with water. Consult a physician. Most important symptoms and effects, both acute and delayed The most important known symptoms and effects are described in the labelling (see section 2.2) and/or in section 11 Indication of any immediate medical attention and special treatment needed no data available SECTION 5: Firefighting measures Extinguishing media Suitable extinguishing media Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide. Special hazards arising from the substance or mixture Carbon oxides, nitrogen oxides (NOx), Hydrogen bromide gas Advice for firefighters Wear self contained breathing apparatus for fire fighting if necessary. Further information no data available SECTION 6: Accidental release measures Personal precautions, protective equipment and emergency procedures Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Avoid breathing dust. For personal protection see section 8. Environmental precautions Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided. Methods and materials for containment and cleaning up Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal. Reference to other sections For disposal see section 13. SECTION 7: Handling and storage Precautions for safe handling Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed. For precautions see section 2.2. Conditions for safe storage, including any incompatibilities Store in cool place. Keep container tightly closed in a dry and well-ventilated place. Recommended storage temperature: 2 - 8 °C Specific end use(s) A part from the uses mentioned in section 1.2 no other specific uses are stipulated SECTION 8: Exposure controls/personal protection Control parameters Components with workplace control parameters Exposure controls Appropriate engineering controls Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday. Personal protective equipment Eye/face protection Safety glasses with side-shields conforming to EN166 Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU). Skin protection Handle with gloves. Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands. The selected protective gloves have to satisfy the specifications of EU Directive 89/686/EEC and the standard EN 374 derived from it. Body Protection Complete suit protecting against chemicals, The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace. Respiratory protection For nuisance exposures use type P95 (US) or type P1 (EU EN 143) particle respirator.For higher level protection use type OV/AG/P99 (US) or type ABEK-P2 (EU EN 143) respirator cartridges. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU). Control of environmental exposure Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided. SECTION 9: Physical and chemical properties Information on basic physical and chemical properties a) AppearanceForm: solid b) Odourno data available c) Odour Thresholdno data available d) pHno data available e) Melting point/freezingno data available point f) Initial boiling point and no data available boiling range g) Flash pointnot applicable h) Evaporation rateno data available i) Flammability (solid, gas) no data available j) Upper/lowerno data available flammability or explosive limits k) Vapour pressureno data available l) Vapour densityno data available m) Relative densityno data available n) Water solubilityno data available o) Partition coefficient: n- log Pow: 4,635 octanol/water p) Auto-ignitionno data available temperature q) Decompositionno data available temperature r) Viscosityno data available s) Explosive propertiesno data available t) Oxidizing propertiesno data available Other safety information no data available SECTION 10: Stability and reactivity Reactivity no data available Chemical stability Stable under recommended storage conditions. Possibility of hazardous reactions no data available Conditions to avoid no data available Incompatible materials Strong oxidizing agents Hazardous decomposition products Other decomposition products - no data available In the event of fire: see section 5 SECTION 11: Toxicological information Information on toxicological effects Acute toxicity no data available Skin corrosion/irritation no data available Serious eye damage/eye irritation no data available Respiratory or skin sensitization no data available Germ cell mutagenicity no data available Carcinogenicity IARC:No component of this product present at levels greater than or equal to 0.1% is identified as probable, possible or confirmed human carcinogen by IARC. Reproductive toxicity no data available Specific target organ toxicity - single exposure no data available Specific target organ toxicity - repeated exposure no data available Aspiration hazard no data available Additional Information RTECS: Not available To the best of our knowledge, the chemical, physical, and toxicological properties have not been thoroughly investigated. SECTION 12: Ecological information Toxicity no data available Persistence and degradability no data available Bioaccumulative potential no data available Mobility in soil no data available Results of PBT and vPvB assessment PBT/vPvB assessment not available as chemical safety assessment not required/not conducted Other adverse effects Very toxic to aquatic life with long lasting effects. no data available SECTION 13: Disposal considerations Waste treatment methods Product Offer surplus and non-recyclable solutions to a licensed disposal company. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber. Contaminated packaging Dispose of as unused product. SECTION 14: Transport information UN number ADR/RID: 3077IMDG: 3077IATA: 3077 UN proper shipping name ADR/RID: ENVIRONMENTALLY HAZARDOUS SUBSTANCE, SOLID, N.O.S. ( (2'Z,3'E)-6- Bromoindirubin-3'-acetoxime) IMDG: ENVIRONMENTALLY HAZARDOUS SUBSTANCE, SOLID, N.O.S. ( (2'Z,3'E)-6- Bromoindirubin-3'-acetoxime) IATA:Environmentally hazardous substance, solid, n.o.s. ( (2'Z,3'E)-6-Bromoindirubin-3'-acetoxime) Transport hazard class(es) ADR/RID: 9IMDG: 9IATA: 9 Packaging group ADR/RID: IIIIMDG: IIIIATA: III Environmental hazards ADR/RID: yesIMDG Marine Pollutant: yesIATA: yes Special precautions for user Further information EHS-Mark required (ADR 2.2.9.1.10, IMDG code 2.10.3) for single packagings and combination packagings containing inner packagings with Dangerous Goods > 5L for liquids or > 5kg for solids. SECTION 15 - REGULATORY INFORMATION N/A SECTION 16 - ADDITIONAL INFORMATION N/A |
| Symbol |
GHS07, GHS09 |
|---|---|
| Signal Word | Warning |
| Hazard Statements | H302-H410 |
| Precautionary Statements | P273-P501 |
| Hazard Codes | N |
| RIDADR | UN 3077 9 / PGIII |