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Boc-Gly-OH is a glycine derivative, mainly used for peptide synthesis and as an important intermediate for various drugs and biotechnological applications.
Synonyms: N-tert-Butoxycarbonyl-2-aminoacetic acid; NSC 127669; Boc-Glycine
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PROTACs Targeting MLKL Protect Cells from Necroptosis
Rathje, Oliver H. ; Perryman, Lara ; Payne, Richard J. , et al. JMC,2023,66(16):11216-11236.
Abstract: Mixed Lineage Kinase domain-Like pseudokinase (MLKL) is implicated in a broad range of diseases due to its role as the ultimate effector of necroptosis and has therefore emerged as an attractive drug target. Here, we describe the development of PROteolysis TArgeting Chimeras (PROTACs) as a novel approach to knock down MLKL through chem. means. A series of candidate degraders were synthesized from a high-affinity pyrazole carboxamide-based MLKL ligand leading to the identification of a PROTAC mol. that effectively degraded MLKL and completely abrogated cell death in a TSZ model of necroptosis. By leveraging the innate ability of these PROTACs to degrade MLKL in a dose-dependent manner, the quant. relationship between MLKL levels and necroptosis was interrogated. This work demonstrates the feasibility of targeting MLKL using a PROTAC approach and provides a powerful tool to further our understanding of the role of MLKL within the necroptotic pathway.
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CAS No. : | 4530-20-5 |
Formula : | C7H13NO4 |
M.W : | 175.18 |
SMILES Code : | O=C(O)CNC(OC(C)(C)C)=O |
Synonyms : |
N-tert-Butoxycarbonyl-2-aminoacetic acid; NSC 127669; Boc-Glycine
|
MDL No. : | MFCD00002690 |
InChI Key : | VRPJIFMKZZEXLR-UHFFFAOYSA-N |
Pubchem ID : | 78288 |
GHS Pictogram: | ![]() |
Signal Word: | Danger |
Hazard Statements: | H318 |
Precautionary Statements: | P280-P305+P351+P338-P310-P403-P501 |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With Lawessons reagent; In dichloromethane; at 25℃; for 16h; | Boc-glycine (2.34 g, 0.134 mmol) was dissolved in dichloromethane (130 mL) and treated with Lawesson's reagent (2.9 g, 0.52 equivalents) and the mixture was stirred at 25 C. for 16 h. The mixture was filtered and the solvents were evaporated. The residue was purified using dichloromethane:ethyl acetate (1:1) to give 2.56 g (100%) of the thioamide. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dmap; dicyclohexyl-carbodiimide; In dichloromethane; at 20℃; | In a flask, 0.1 g Irinotecan (0.1704 mmoles), 0.059 g t-Boc-Glycine (0.3408 mmoles), and 0.021 g DMAP (0.1704 mmoles) were dissolved in 13 mL of anhydrous dichloromethane (DCM). To the solution was added 0.070 g DCC (0.3408 mmoles) dissolved in 2 mL of anhydrous DCM. The solution was stirred overnight at room temperature. The solid was removed through a coarse frit, and the solution was washed with 10 mL of 0.1N HCL in a separatory funnel. The organic phase was further washed with 10 mL of deionized H2O in a separatory funnel and then dried with Na2SO4. The solvent was removed using rotary evaporation and the product was further dried under vacuum. 1H NMR (DMSO): delta 0.919 (t, CH2CH3), 1.34 (s, C(CH3)3), 3.83 (m, CH2), 7.66 (d, aromatic H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 4-methyl-morpholine; In ethyl acetate; N,N-dimethyl-formamide; | 1. t-Butyloxycarbonyl-glycyl-L-aspartic acid dibenzyl ester t-Butyloxycarbonyl-glycine (7.1 g) was dissolved in ethyl acetate (50 ml), cooled to -10 to -15 C. with stirring and treated with N-methylmorpholine (5.6 ml) followed by isobutyl chloroformate (5.18 ml). The mixture was stirred at -15 C. for 10 minutes. Meanwhile, L-aspartic acid dibenzyl ester p-tosylate salt (2.1 g) was dissolved in dimethyl formamide (80 ml), cooled to -10 C. and neutralized by adding N-methylmorpholine (5.6 ml). This solution was added to the above solution of the preformed mixed anhydride and the reaction mixture allowed to warm slowly to room temperature with stirring over 3 hours. The reaction mixture was then diluted with ethyl acetate (300 ml) and the solution washed with brine (twice) followed by 4% aqueous sodium bicarbonate, water, 5% aqueous citric acid and finally with water to neutrality. The organic phase was dried (magnesium sulfate) and then evaporated to an oil. Yield: 20 g. The product was homogeneous by TLC (System: chloroform:methanol:acetic acid, 360:32:8; Rf =0.8). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
46% | With trifluoromethanesulfonic acid anhydride; N-ethyl-N,N-diisopropylamine; In dichloromethane; ethyl acetate; | a) Preparation of 2-(2-maleimidoethoxy)ethanol above (2.70 mmoles) was added 10 mL of methylene chloride, and the solution cooled to 0°. To the solution was added 1.11 g of 2,6-di-tertbutyl-4-methylpyridine (2.70 mmoles, 100 molpercent) followed by 0.45 mL of trifluoromethanesulfonic anhydride (2.70 mmoles, 100 molpercent). The heterogeneous mixture was stirred at 0° for 1 h. The solution was filtered, and to the filtrate was added a solution of 0.47 g of N-tBOC-glycine (2.70 mmoles, 100 molpercent) and 0.47 mL of diisopropylethylamine (2.70 mmoles, 100 molpercent) in 10 mL of CH2 Cl2. The mixture was stirred for 2 h at room temperature. Ethyl acetate (100 mL) was added and the solution extracted with water (1*50 mL) then dried over Na2S04. Filtration and removal of solvent gave an oil which was purified by flash chromatography on 100 mL of silica gel. The column was eluted with 400 mL of EtOAc/hexanes 1:1, giving 0.43 g of pure material (1.26 mmoles, 46percent). NMR (300 MHz, CDCl3) delta1.45 (s, 9H), 3.66 (m, 6H) 3.94(d, 2H), 4.26 (t, 2H), 5.14 (m, 1H), 6.74 (s, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; for 8h; | EXAMPLE 39 Preparation of tert-butyl 2-(isoquinolin-6-ylamino)-2-oxoethyl carbamate (F39) To N-Boc-glycine in DMF was added EDC, HOBT and <strong>[23687-26-5]6-aminoisoquinoline</strong>. This mixture was stirred for 8 hours. The reaction was washed with NaHCO3(sat), extracted with EtOAc, dried (Na2SO4), filtered and evaporated. Column chromatography (SiO2, MeOH/CH2Cl2) gave tert-butyl 2-(isoquinolin-6-ylamino)-2-oxoethyl carbamate (E39). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1. Weigh 175 mg Boc-glycine and 150 mg NMM into 20 mL THF.2. Add 100mg of isobutyl chloroformate under nitrogen atmosphere at 0 ° C and react at 0 ° C for 30min.3. To the above reaction solution was added 87.5mg CABT (purchased from Shanghai Ou Kun Chemical Co., Ltd.), the reaction was stirred at 0 ° C 2h, then stirred at room temperature for 12h.4. To the above reaction solution was added 100 mL of saturated NaHCO 3, extracted with 3 × 150 mL of ethyl acetate, and the organic phase was dried over anhydrous sodium sulfate.5. After removing the organic phase by rotary evaporation under reduced pressure, the product was purified by column chromatography on silica gel. The final product Boc-glycine-CBT was eluted with dichloromethane: methanol (10: 1-5: 1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dmap; diisopropyl-carbodiimide; In dichloromethane; at 4 - 20℃; for 3h; | IRI (61.9 mg, 0.1 mmol), Boc-Gly-OH (18 mg, 0.1 mmol), andDMAP (12 mg, 0.1 mmol) were dissolved in DCM (10 mL), cooledto 4 C, combined with DIPCDI (31 lL, 0.2 mmol) and stirred for3 h at room temperature. The reaction mixture was washed anddried as above. The residue was dissolved in 50percentTFA/DCM (1 mL)and solidified as above to give H2N-Gly-IRI TFA salt. To a solutionof this salt in dioxane (1 mL) EMCA (44 mg, 0.2 mmol) was added,followed by pyridine (17 lL, 0.1 mmol) and DIPCDI (16 lL,0.1 mmol). The mixture was stirred for a further 3 h at room temperatureand solidified with diethyl ether to give 5 (55 mg, 64percentyield). | |
4.02 g | With dmap; dicyclohexyl-carbodiimide; In dichloromethane; at 20℃; for 4h; | BGC0222-SM1 (Irinotican, 3.50g,1.0eq) and DMF (52.5 mL) were added into a 250 mL round-bottomed flask. DMF wasremoved under reduced pressure at 60 oC. Then n-heptane (100 mL) was added and removed under reduced pressure for three times. DCM (105 mL), Boc-Gly-OH(1.08 g, 1.2 eq) and DMAP (63 mg, 0.1 eq) were added. DCC (1.59 g, 1.5 eq)dissolved in DCM (10 mL) was added into the reaction under 20 oC. The mixture was reactedfor 4 h until the reaction was completed (monitored by TLC). The mixture wasfiltered, IPA (120 mL) was added to the liquid, the solution was condensed toabout 30 mL and was poured into n-heptane (150 mL) to give white solid. Thesuspension was stirred for 1 h. The solid was filtered out and washed withn-heptane (30 mL*2) to give pale yellow solid BGC0222dwith 4.02 g. 1HNMR (400MHz, DMSO-d6): delta 0.93 (3H, t, J= 7.20 Hz), 1.04 (1H,d, J= 6.40 Hz), 1.25~1.31 (4H, m), 1.34~1.40 (9H, m), 1.76~1.85 (6H, m),2.11~2.19 (4H, m), 2.97~3.22 (6H, m), 3.38~3.41(2H, m), 3.79~3.85 (1H, m),3.92~3.98 (1H, m), 4.19~4.42 (2H, m), 5.29~5.40 (2H, m), 5.52 (2H, s), 7.21(1H, s), 7.43 (1H, H, t, J= 6.00 Hz), 7.69 (1H, dd, J= 2.40 Hz; 7.20 Hz), 8.00 (1H, d, J= 2.40 Hz), 8.13~8.17 (1 H, m);10.67 (1H, s); 13C NMR (100MHz, DMSO-d6)delta 169.99, 167.59, 157.01, 156.32,153.03, 152.07, 150.32, 146.84, 146.75, 145.70, 145.61, 131.35, 128.93, 127.48,126.39, 119.19, 115.46, 95.89, 78.94, 76.66, 66.72, 62.49, 50.02, 49.45, 43.45,43.06, 42.54, 31.72, 30.78, 28.64, 28.31, 26.21, 25.96, 25.87, 23.07, 22.69, 22.57,22.16, 14.42, 7.97. LC/MS (m/z): calcd for C40H49N5O9 743.35;found 744 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 20℃; for 1h; | Methyl 3-(2-aminoacetamido)-4-fluorobenzoate (I-58)HATU (8.2 mmol) was added to a mixture of N-Boc glycine (6.8 mmol), <strong>[369-26-6]methyl 3-amino-4-fluorobenzoate</strong> (6.2 mmol), diisopropylethylamine (3.6 mL, 20.5 mmol) and DMF (15 mL). The reaction was stirred at room temperature for 1 hr. LCMS indicated that the reaction was complete. The reaction was diluted with water and extracted with ethyl acetate. The organic extracts were dried over MgSC and concentrated. No further purification was necessary. The crude amide (I-57) (9.2 mmol) was dissolved in dichloromethane (15 mL) and treated with trifluoroacetic acid (8 mL). The reaction stirred at room temperature for 1 hr. LCMS indicated that the reaction was complete. The reaction was concentrated to dryness and the crude material was purified by preparative HPLC to give I-58. | |
To a 40 mL reaction vessel was added reagents in the following order: N-(tert- butoxycarbonyl)glycine (1.0 mmol), THF (4.0 mL), N-methyl morpholine (c.a. 0.2 mL, 2.0 mmol). This was stirred until complete dissolution. Next was added 2-chloro-4,6-dimethoxy-1,3,5- triazine (1.0 mmol) and this solution was stirred for 20 mins at 50 °C until a white precipitate fully formed. The precipitate was physically agitated to ensure all solids were well stirred. Next was added <strong>[369-26-6]methyl 3-amino-4-fluorobenzoate</strong> (1.3 mmol) and the reaction was stirred for 30 mins at 50 °C and then at room temperature for 2 hrs, then diluted with 5 mL of MeOH and then purified by being poured into water (rapidly stirred, 25 mL). A white solid was collected and treated with dichloromethane (5 mL) and TFA (5 mL), and heated to 34 °C for about 1 hr until removal of the Boc group was complete (by LCMS monitoring). The material was concentrated to dryness and subjected to reverse-phase chromatography (10 to 40 percent water/ACN) to give I-69. The desired fractions were then passed through polymer bound ion- exchange free base cartridges to removal any residual TFA (using product Stratospheres, SPE PL HC03 MP SPE 0.9 mmol nominal load x 2 units). Mobilizing eluent was MeOH (10 mL total flush volume). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 16h; | General procedure: To a solution of carboxylic acid 19 (300 mg, 1.13 mmol), in dry DMF (5 mL), under N2 atmosphere and cooled to 0 °C, were added TBTU (363 mg, 1.13 mmol) and DIPEA (6.18 mL, 39.55 mmol). After 30' a 0 °C, 5-amine-2-oxindole (168 mg, 1.13 mmol) was added and the temperature was kept at 0 °C for additional 30'. Later the mixture was slowly warmed to room temperature and left under stirring at rt overnight. Once TLC verified the disappearance of the precursor, the organic solvent was evaporated under vacuum and the crude product was purified by flash chromatography over silica gel, using 0-4percent MeOH as a gradient in CHCl3, to obtain pure 1 as a white solid (210 mg, 0.53 mmol, 47percent yield). |
86% | With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine; | N-Boc derivative 1a (2.64 mmol) was reacted through a condensation reaction with 5-amino-indol-2-one (391 mg, 2.64 mmol), in the presence of the condensing agent TBTU (848 mg, 2.64 mmol) and DIPEA (5.28 mmol, 0.92 ml_) as a base. The amide was obtained after purification of the crude product by column chromatography over silica gel using CHC /MeOH 92:8 as the eluent (693 mg, 2.27 mmol, 86percent yield).1 H-N MR (400 MHz, DMSO-de): delta 1 .39 (s, 9H, Boc); 3.46 (s, 2H, CH2 indole); 3.68 (d, 2H, J = 6.0 Hz, CH2 glycine); 6.73 (d, 1 H, J = 8.2 Hz, Ar); 7.00 (t, 1 H, J = 6.0 Hz, NH); 7.32 (dd, 1 H, J =2.0, 8.2 Hz, Ar); 7.49 (s, 1 H, Ar); 9.74 (br s, 1 H, NH); 10.27 (br s, 1 H, NH) ppm. Anal. Calcd for C15H19N3O4: C, 59.01 percent; H, 6.27percent; N 13.76percent; Found: C, 59.10percent; H, 6.19percent; N, 13.99percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dicyclohexyl-carbodiimide; In N,N-dimethyl-formamide; at 20℃; | A mixture of 2-(tert-butoxycarbonylamino) acetic acid (1.75 g, 10 mmol), 5,6- diamino-1-methylpyrimidine-2,4(1H,3H)-dione (1.56 g, 10 mmol), DCC (8.25 g, 40 mmol) in DMF (40 mL) was stirred at rt overnight. The mixture was diluted with H20 (300 mL) and stirred for 30 mm, then filtered. The filtrate was concentrated in vacuo to give crude product which was purified by flash column chromatography (MeOHIDCM 10percent30percent) to give tertbutyl 2-(6-amino- 1 -methyl-2,4-dioxo- 1,2,3 ,4-tetrahydropyrimidin-5 -ylamino)-2- oxoethylcarbamate; ESI: m/z 314.2 (M+H)t This product (700 mg, 2.23 mmol) and NaOH (1 N aqueous, 9 mL, 9.00 mmol ) in EtOH (90 mL) was heated to 50 °C overnight. The solvent was concentrated in vacuo and the residue was diluted with H20 (100 mL). The pH was adjusted to 7.0 with iN HC1. The precipitate was collected by filtration and dried under vacuum. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
21% | General procedure: Solid-phase peptide synthesis was carried out on Fmoc-cappedpolystyrene rink amide MBHA resin (100-200 mesh, 0.05-0.15 mmol scale). The following amino acidderivatives suitable for Fmoc SPPS were used: Fmoc-Cys(Trt)-OH, Fmoc-Gly-OH, Fmoc-Glu(tBu)-OH,Fmoc-Trp(Boc)-OH, Fmoc-Ala-OH, Fmoc-Tyr(tBu)-OH, Fmoc-Asn(Trt)-OH, Fmoc-Pro-OH, Fmoc-Thr(tBu)-OH, Fmoc-Lys(Boc)-OH, Fmoc-Phe-OH, Fmoc-Val-OH, Fmoc-aPhe-OH, Fmoc-aVal-OH,Fmoc-aTyr(tBu)-OH, Fmoc-(N-Me)-Phe-OH, Fmoc-D-Ser(TBS)-OH, Fmoc-D-hSer(TBS)-OH, Boc-Gly-OH. Dry resin was washed with DMF 3x and allowed to swell in DMF for 2 h prior to use. Allreactions were carried out using gentle agitation. Fmoc deprotection steps were carried out by treating theresin with a solution of 20percent piperidine/DMF (15 min x 2). Coupling of Fmoc-protected amino acids aswell as (N2-Boc)-hydrazino acids was effected using 5 equiv. HATU (0.5 M in DMF), 10 equiv. DIEA(1.0 M in DMF), and 5 equiv. of the carboxylic acid in DMF at 50 oC (1 h). Coupling of residues Nterminalto the hydrazino acids was carried out with 30 equiv. collidine and 10 equiv. of pre-formed Fmocamino acid chlorides (or 10 equiv. of Fmoc amino acids with 3.3 equiv. triphosgene) in THF at rt (1 h x2).3 After each reaction the resin was washed with DMF 2x, DCM 1x, then DMF 1x. Peptides undergoingMitsunobu reactions were capped with Boc-Gly-OH, washed with DCM 3x, and treated with 5 equiv.TBAF in THF for 3 h at rt. After the reaction the resin was washed with DCM 3x and then treated with 5equiv. triphenylphosphine in THF followed by 5 equiv. of DIAD, then strirred overnight at rt. Peptideswere cleaved from the resin by incubating with gentle stirring in 2 mL of 95:5 TFA:H2O at rt for 2 h. Thecleavage mixture was filtered and the resin was rinsed with an additional 1 mL of cleavage solution. Thefiltrate was treated with 8 mL of cold Et2O to induce precipitation. The mixture was centrifuged and thesupernatant was removed. The remaining solid was washed 2 more times with Et2O and dried undervacuum. Cysteine-containing peptides were purified, lyophilized, dissolved in 10mM phosphate buffer(pH 8.9, 5percent v/v DMSO), stirred until analytical HPLC and MS showed complete conversion to the cyclicdisulfide (1-2 d), and then repurified. Peptides were analyzed and purified on C12 RP-HPLC columns(preparative: 4mu, 90A, 250 x 21.2 mm; analytical: 4mu, 90A, 150 x 4.6 mm) using linear gradients ofMeCN/H2O (with 0.1percent formic acid), then lyophilized to afford white powders. All peptides werecharacterized by LCMS (ESI), HRMS (ESI-TOF), and 1H NMR. Analytical HPLC samples for all purifiedpeptides were prepared as 1 mM in H2O containing 20 mM phosphate buffer at pH 7.0. Linear gradientsof MeCN in H2O (0.1percent formic acid) were run over 20 minutes and spectra are provided for lambda = 220 nm. |
Tags: 4530-20-5 synthesis path| 4530-20-5 SDS| 4530-20-5 COA| 4530-20-5 purity| 4530-20-5 application| 4530-20-5 NMR| 4530-20-5 COA| 4530-20-5 structure
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P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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