- Ivermectin
- A 438079
- A 438079 hydrochloride
- A-317491
- KN-92 hydrochloride
| KN-93CaMKII inhibitor,selective and cometitive |
Sample solution is provided at 25 µL, 10mM.
Nature.2017 Jan 19;541(7637):417-420.
Nature.2018 Nov;563(7731):407-411.Nature.2018 Jun 13.Nature.2018 Jun 27.Nature.2018 Mar 29;555(7698):673-677.Nature.2017 Sep 7;549(7670):96-100.Nature.2016 Apr 21;532(7599):398-401.
Science.2016 Aug 5;353(6299)594-8Nat Nanotechnol.2017 Dec;12(12):1190-1198.Nature Biotechnology.2017 Jun;35(6):569-576Nat Med.2018 Sep 17.Cell.2018 Dec 21. pii: S0092-8674(18)31561-7.Cell.Available online 25 October 2018.Cell.2018 Sep 27. pii: S0092-8674(18)31183-8.Cell.2018 Jun 28;174(1):172-186.e21.Cell.2018 Feb 22;172(5):1007-1021.e17.Cell.2017 Nov 30;171(6):1284-1300.e21.Cell.2017 Aug 17. pii: S0092-8674(17)30869-3.Cell.2017 Jul 13;170(2):312-323Nat Med.2018 Jan 29.Nat Med.2017 Nov;23(11):1342-1351.Cell.2017 Apr 6;169(2):286-300.Cell.2015 Aug 27;162(5):987-1002.Cell.2015 Feb 12;160(4):729-44.Nature Medicine.2017 Apr;23(4):493-500.Cancer Cell.2018 May 14;33(5):905-921.e5.Cancer Cell.2018 Apr 9;33(4):752-769.e8.Cancer Cell.2018 Mar 12;33(3):401-416.e8.Cancer Cell.2017 Aug 14;32(2):253-267.e5.Nat Methods.2018 Jul;15(7):523-526.Cell Stem Cell.2018 May 3;22(5):769-778.e4.Cell Stem Cell.2017 Nov 20. pii: S1934-5909(17)30375-2.Quality Control & MSDS
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- Purity = 98.68%
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Chemical structure
| Description | KN-93 is a selective and competitive inhibitor of Ca2+/calmodulin-dependent kinase type II (CaMKII) with Ki value of 370 nM. | |||||
| Targets | CaMKII | |||||
| IC50 | 370 nM (Ki) | |||||
| Kinase experiment [1]: | |
Measurement of activities of autophosphorylated/non-autophosphorylate CaMKII | CaMKII activity was measured utilizing syntideII as a substrate. Purified CaMKII was pre-incubated in the assay mixture (35 mM Hepes-Na ( pH 8.0), 10 mM MgC12, 0.5 μM CaM, 5 μM ATP, 1 mM CaCl2 or 1 mM EGTA, total 25 μL) at 30°C for 2 mins. After this pre-incubation, the protein substrate/radioactive ATP mixture was added to the same test tube and the preparation was further incubated at 30°C, for 5 mins (final assay condition: 35 mM Hepes-Na (pH 8.0), 10 mM MgCl2, 0.125 μM CaCl2, 20 μM syntideII, 11.25 μM [γ-32P] ATP, 10 % DMSO and indicated concentrations of KN-93, supplemented with 0.25 mM CaCl2 and 2 mM EGTA (for autophosphorylated samples) or 0.25 mM EGTA and 2 mM CaCl2 (for nonautophosphorylated samples ), total 100 μL). The reaction was terminated by adding of 25 μL of 100 % (w/v) ice-cold TCA. After centrifugation, 80 μL of the supernatant was applied to phosphocellulose paper. The filters were then washed with 75 mM H3PO4 for 15 mins with continuous agitation. After 4-cycles of washing, the radioactivity retains on the filter paper was quantified in a liquid scintillation counter. |
| Cell experiment [2]: | |
Cell lines | NIH 3T3 fibroblasts |
Preparation method | The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
Reaction Conditions | ~ 24 μM; 70 hrs |
Applications | KN-93 inhibited serum-induced fibroblast cell growth with an IC50 value of 8 μM, and induced apoptosis after prolonged G1 arrest at the concentration of 24 μM. |
| Animal experiment [3]: | |
Animal models | Parkinson’s disease (PD) rats |
Dosage form | 1, 2 or 5 μg; intrastriatal administration; b.i.d., for 21 days |
Applications | In PD rats, KN-93 (5 μg) ameliorated levodopa-induced dyskinesia through lowering the expression of pGluR1S845. |
Other notes | Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
References: [1]. Sumi M, Kiuchi K, Ishikawa T, Ishii A, Hagiwara M, Nagatsu T, Hidaka H. The newly synthesized selective Ca2+/calmodulin dependent protein kinase II inhibitor KN-93 reduces dopamine contents in PC12h cells. Biochem Biophys Res Commun. 1991 Dec 31;181(3):968-75. [2]. Tombes RM, Grant S, Westin EH, Krystal G: G1 cell cycle arrest and apoptosis are induced in NIH 3T3 cells by KN-93, an inhibitor of CaMK-II (the multifunctional Ca2+/CaM kinase). Cell Growth Differ 1995, 6(9):1063-1070. [3]. Yang X, Wu N, Song L, Liu Z. Intrastriatal injections of KN-93 ameliorates levodopa-induced dyskinesia in a rat model of Parkinson"s disease. Neuropsychiatr Dis Treat. 2013;9:1213-20. | |
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| Cas No. | 139298-40-1 | SDF | Download SDF |
| Synonyms | KN 93;KN93 | ||
| Chemical Name | N-[2-[[[(E)-3-(4-chlorophenyl)prop-2-enyl]-methylamino]methyl]phenyl]-N-(2-hydroxyethyl)-4-methoxybenzenesulfonamide | ||
| Canonical SMILES | CN(CC=CC1=CC=C(C=C1)Cl)CC2=CC=CC=C2N(CCO)S(=O)(=O)C3=CC=C(C=C3)OC | ||
| Formula | C26H29ClN2O4S | M.Wt | 501.04 |
| Solubility | ≥19.15mg/mL in DMSO | Storage | Store at -20°C |
| Physical Appearance | A solid | Shipping Condition | Evaluation sample solution : ship with blue ice.All other available size:ship with RT , or blue ice upon request |
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. | ||
KN-93 is a potent and selective inhibitor of CaM kinase II with IC50 value of 0.37μM.[1]CaM kinase II means Ca2+/calmodulin-dependent protein kinase II which is a serine/threonine-specific protein kinase. It is regulated by the Ca2+/calmodulin complex. CaMKII has 28 different isoforms. The structure governs an autoinhibition which is the Threonine 286 residue. When this site is phosphorylated, it will permanently activate the CaMKII enzyme. The variable and self-associative domains of CaMKII enzyme govern the sensitivity to calcium and calmodulin. CaMKII is related to many signaling pathways. CaMKII is considered to play an important role in learning and memory. CaMKII is also important for reuptake in cardiomyocytes and Ca2+ homeostasis, and CD8 T-cell activation. Misregulation of CaMKII is considered to be related to Alzheimer’s disease, heart arrhythmia , and Angelman syndrome.[2]KN-93 significantly inhibited CaM kinase activity at 0.5μM in vitro CaM kinase assay. KN-93 potent inhibited CaM kinase II activity In vitro CaM kinase activity with rabbit myocardium with Ki value of 2.58μM. [1] KN-93 inhibited cell growth at 12μM in NIH 3T3 cells and arrested cells in G1 cycle. KN-93 induced cell apoptosis at 24μM in NIH 3T3 cells. [3] KN-93 inhibits expression of Mcl-1which is an anti-apoptotic protein, It also induces p53-independent cell death in PCa cells. KN-93 also induces the generation of ROS and inhibits AR activity then induces cell death. References: [1]. Anderson ME, Braun AP, Wu Y, Lu T, Schulman H, Sung RJ: KN-93, an inhibitor of multifunctional Ca++/calmodulin-dependent protein kinase, decreases early afterdepolarizations in rabbit heart. J Pharmacol Exp Ther 1998, 287(3):996-1006.[2]. Yamauchi T: Neuronal Ca2+/calmodulin-dependent protein kinase II--discovery, progress in a quarter of a century, and perspective: implication for learning and memory. Biol Pharm Bull 2005, 28(8):1342-1354.[3]. Tombes RM, Grant S, Westin EH, Krystal G: G1 cell cycle arrest and apoptosis are induced in NIH 3T3 cells by KN-93, an inhibitor of CaMK-II (the multifunctional Ca2+/CaM kinase). Cell Growth Differ 1995, 6(9):1063-1070.
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胰蛋白酶Trypsin (Parenzyme) 为蛋白酶的一种，EC 3.4.4.4，是从牛、羊、猪的胰脏提取的一种丝氨酸蛋白水解酶。在脊椎动物中，作为消化酶而起作用。在胰脏是作为酶的前体胰蛋白酶原而被合成的。作为胰液的成分而分泌，受肠激酶，或胰蛋白酶的限制分解成为活化胰蛋白酶，是肽链内切酶，它能把多肽链中赖氨酸和精氨酸残基中的羧基侧切断。它不仅起消化酶的作用，而且还能限制分解糜蛋白酶原、羧肽酶原、磷脂酶原等其它酶的前体，起活化作用。是特异性最强的蛋白酶，在决定蛋白质的氨基酸排列中，它成为不可缺少的工具。
明白了么，少年？
共价调节酶（covalent regulatory enzyme） 是一类由其它酶对其结构进行可逆共价修饰，使其处于活性和非活性的互变状态，从而调节酶活性。共价调节酶一般都存在相对无活性和有活性两种形式，两种形式之间互变的正、逆向反应由不同的酶催化。磷酸化是可逆共价修饰中最常见的类型。因为信号激酶能作用于很多靶分子，通过磷酸化作用信号能被极大地放大。蛋白激酶的调节作用能被催化水解磷酸基团的蛋白质磷酸酶逆转。通过磷酸化和脱磷酸化作用，使酶在活性形式和非活性形式之间互变。
别构调节：酶分子的非催化部位与某些化合物可逆地非共价结合后发生构象的改变，进而改变酶活性状态，称为酶的别构调节。有些酶分子在空间至少有两个不同的部位，一个为催化部位，一个为调节部位。某些物质可以与这种酶的调节部位相互作用而使酶分子构象发生改变，进而使催化部位受到影响，导致酶的催化活性改变，这种现象称为酶的别构调节,或称别位调节、变构调节
蛋白酶分布广泛,主要存在于人和动物消化道中，而消化道通过口与肛门与外界相通，属于外环境或外界环境
（溶菌酶、凝血酶原等）分布在内环境
（消化）酶分布在消化道
食物酶：
天然存在於所有的生食物中。他们是消化酶的外部来源。食物酶在烹饪和处理过程中很容易被破坏。
一些富含酶的食物:
青木瓜内含丰富的木瓜酵素、木瓜蛋白酶、凝乳蛋白酶、胡萝卜素。
绿豆富含维生素B族、葡萄糖、蛋白质、淀粉酶、氧化酶。
生的蔬菜水果坚果种子富含各种酶，如菠菜、海藻等。
胡萝卜富含维生素C分解酶，萝卜、香瓜、菜花富含过氧化物酶，南瓜含维生素C分解酶，蕨菜含有维生素B1分解酶，菠萝和猕猴桃富含蛋白酶，无花果富含淀粉酶和蛋白酶，纳豆菌中富含淀粉酶、纤维酶。
人体内存在大量酶，结构复杂，种类繁多，到目前为止，已发现3000种以上（即多样性）．如米饭在口腔内咀嚼时，咀嚼时间越长，甜味越明显，是由于米饭中的淀粉在口腔分泌出的唾液淀粉酶的作用下，水解成麦芽糖的缘故．因此，吃饭时多咀嚼可以让食物与唾液充分混合，有利于消化．此外人体内还有胃蛋白酶，胰蛋白酶等多种水解酶．人体从食物中摄取的蛋白质，必须在胃蛋白酶等作用下，水解成氨基酸，然后再在其它酶的作用下，选择人体所需的20多种氨基酸，按照一定的顺序重新结合成人体所需的各种蛋白质，这其中发生了许多复杂的化学反应．可以这样说，没有酶就没有生物的新陈代谢，也就没有自然界中形形色色、丰富多彩的生物界．
