| 词条 | H-89 |
| 释义 |
| Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 443142728 | ImageFile = H 89 dihydrochloride.svg | ImageSize = | IUPACName = N-[2-[[3-(4-Bromophenyl)-2-propenyl]amino]ethyl]-5-isoquinolinesulfonamide | OtherNames = |Section1={{Chembox Identifiers | IUPHAR_ligand = 5983 | CASNo_Ref = {{cascite|correct|??}} | CASNo = 127243-85-0 | SMILES = c1cc2cnccc2c(c1)S(=O)(=O)NCCNC/C=C/c3ccc(cc3)Br | PubChem = 449241 | ChEMBL_Ref = {{ebicite|changed|EBI}} | ChEMBL = 104264 | ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} | ChemSpiderID = 395827 | ChEBI_Ref = {{ebicite|changed|EBI}} | ChEBI = 47495 | InChI = 1/C20H20BrN3O2S/c21-18-8-6-16(7-9-18)3-2-11-22-13-14-24-27(25,26)20-5-1-4-17-15-23-12-10-19(17)20/h1-10,12,15,22,24H,11,13-14H2/b3-2+ | InChIKey = ZKZXNDJNWUTGDK-NSCUHMNNBL | StdInChI_Ref = {{stdinchicite|changed|chemspider}} | StdInChI = 1S/C20H20BrN3O2S/c21-18-8-6-16(7-9-18)3-2-11-22-13-14-24-27(25,26)20-5-1-4-17-15-23-12-10-19(17)20/h1-10,12,15,22,24H,11,13-14H2/b3-2+ | StdInChIKey_Ref = {{stdinchicite|changed|chemspider}} | StdInChIKey = ZKZXNDJNWUTGDK-NSCUHMNNSA-N |Section2={{Chembox Properties | Formula = |C=20|H=20|Br=1|N=3|O=2|S=1 | MolarMass = | Appearance = | Density = | MeltingPt = | BoilingPt = | Solubility = Soluble to 25 mM in Water | SolubleOther = up to 100 mM DMSO |Section3={{Chembox Hazards | MainHazards = Exposure may cause irritation to eyes, mucous membranes, upper respiratory tract and skin. | RPhrases = | SPhrases = S22 - Do not breathe dust S24/25 - Avoid contact with skin and eyes S36/37/39 - Wear suitable protective clothing, gloves and eye/face protection | RSPhrases = | FlashPt = | AutoignitionPt = }}H-89 is a protein kinase inhibitor with greatest effect on protein kinase A (PKA).[1] H-89, derived from H-8 (N-[2-(methylamino)ethyl]-5-isoquinoline-sulfonamide),[2] was initially believed to act specifically as an inhibitor of PKA,[3] being 30 times more potent than H-8 at inhibiting PKA and 10 times less potent at inhibiting protein kinase G. It achieves this through competitive inhibition of the adenosine triphosphate (ATP) site on the PKA catalytic subunit.[4] However, subsequent work has suggested a variety of additional effects such as inhibition of other protein kinases (IC50 values of 80, 120, 135, 270, 2600 and 2800 nM for S6K1, MSK1, PKA, ROCKII, PKBα and MAPKAP-K1b respectively),[5] and direct inhibition of various potassium currents.[6] In addition to its use in studying mechanisms of cell signalling, H-89 has also been used experimentally in vivo. H-89 has been shown to increase the threshold and latency of pentylenetetrazol-induced seizures [7] and decrease morphine withdrawal symptoms in mice.[8] References1. ^{{cite journal |last1=Marunaka |first1=Yoshinori |last2=Niisato |first2=Naomi |title=H89, an inhibitor of protein kinase A (PKA), stimulates Na+ transport by translocating an epithelial Na+ channel (ENaC) in fetal rat alveolar type II epithelium |journal=Biochemical Pharmacology |volume=66 |issue=6 |pages=1083–9 |year=2003 |pmid=12963496 |doi=10.1016/S0006-2952(03)00456-8 }} {{organic-compound-stub}}2. ^{{Cite journal|last=Hidaka|first=H.|last2=Inagaki|first2=M.|last3=Kawamoto|first3=S.|last4=Sasaki|first4=Y.|date=1984-10-09|title=Isoquinolinesulfonamides, novel and potent inhibitors of cyclic nucleotide dependent protein kinase and protein kinase C|journal=Biochemistry|volume=23|issue=21|pages=5036–5041|issn=0006-2960|pmid=6238627|doi=10.1021/bi00316a032}} 3. ^{{Cite journal|last=Chijiwa|first=T.|last2=Mishima|first2=A.|last3=Hagiwara|first3=M.|last4=Sano|first4=M.|last5=Hayashi|first5=K.|last6=Inoue|first6=T.|last7=Naito|first7=K.|last8=Toshioka|first8=T.|last9=Hidaka|first9=H.|date=1990-03-25|title=Inhibition of forskolin-induced neurite outgrowth and protein phosphorylation by a newly synthesized selective inhibitor of cyclic AMP-dependent protein kinase, N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89), of PC12D pheochromocytoma cells|journal=The Journal of Biological Chemistry|volume=265|issue=9|pages=5267–5272|issn=0021-9258|pmid=2156866}} 4. ^{{cite journal |last1=Murray |first1=A. J. |title=Pharmacological PKA Inhibition: All May Not Be What It Seems |journal=Science Signaling |volume=1 |issue=22 |pages=re4 |year=2008 |pmid=18523239 |doi=10.1126/scisignal.122re4 }} 5. ^{{cite journal |last1=Lochner |first1=A. |last2=Moolman |first2=J. A. |title=The Many Faces of H89: A Review |journal=Cardiovascular Drug Reviews |volume=24 |issue=3–4 |pages=261–74 |year=2006 |pmid=17214602 |doi=10.1111/j.1527-3466.2006.00261.x }} 6. ^{{Cite journal|last=Pearman|first=Charles|last2=Kent|first2=William|last3=Bracken|first3=Nicolas|last4=Hussain|first4=Munir|date=August 2006|title=H-89 inhibits transient outward and inward rectifier potassium currents in isolated rat ventricular myocytes|journal=British Journal of Pharmacology|volume=148|issue=8|pages=1091–1098|doi=10.1038/sj.bjp.0706810|issn=0007-1188|pmc=1752020|pmid=16799649}} 7. ^{{cite journal |last1=Hosseini-Zare |first1=Mahshid Sadat |last2=Salehi |first2=Forouz |last3=Seyedi |first3=Seyedeh Yalda |last4=Azami |first4=Kian |last5=Ghadiri |first5=Tahereh |last6=Mobasseri |first6=Mohammad |last7=Gholizadeh |first7=Shervin |last8=Beyer |first8=Cordian |last9=Sharifzadeh |first9=Mohammad |title=Effects of pentoxifylline and H-89 on epileptogenic activity of bucladesine in pentylenetetrazol-treated mice |journal=European Journal of Pharmacology |volume=670 |issue=2–3 |pages=464–70 |year=2011 |pmid=21946102 |doi=10.1016/j.ejphar.2011.09.026 }} 8. ^{{cite journal |last1=Seyedi |first1=Seyedeh Y. |last2=Salehi |first2=Forouz |last3=Payandemehr |first3=Borna |last4=Hossein |first4=Sara |last5=Hosseini-Zare |first5=Mahshid S. |last6=Nassireslami |first6=Ehsan |last7=Yazdi |first7=Behnoosh B. |last8=Sharifzadeh |first8=Mohammad |title=Dual effect of cAMP agonist on ameliorative function of PKA inhibitor in morphine-dependent mice |journal=Fundamental & Clinical Pharmacology |volume=28 |issue=4 |pages=445–54 |year=2014 |pmid=24033391 |doi=10.1111/fcp.12045 }} 4 : Isoquinolines|Organobromides|Sulfonamides|Protein kinase inhibitors |
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