| 名稱 | Longdaysin |
| 描述 | Longdaysin is an inhibitor of CK1α and CK1δ (IC50s: 5.6/8.8 μM). It also can inhibit ERK2 (IC50: 52 μM). |
| 細(xì)胞實(shí)驗(yàn) | 2×10^5 cells were suspended in 100 μL serum-free medium containing the indicated concentrations of longdaysin, and then seeded in 24-transwell chambers with 8 μm pore membrane. The lower chamber contained medium with 20% FBS. After incubation at 37°C for 6 hours, the unmigrated cells on the upper side of membrane were removed by a cotton swab, and the migrated cells were stained with crystal violet and stained cells were photomicrographed. For invasion assays, the transwell chambers with 8 μm pore membranes were coated with Matrigel [2]. |
| 激酶實(shí)驗(yàn) | The CKIδ, CKIα, CDK7, and ERK2 kinase assays were performed on 384-well plates (10 μl volume). The reaction mixture was as follows: for CKIδ, 2 ng/μl CKIδ, 50 μM peptide substrate RKKKAEpSVASLTSQCSYSS corresponding to human PER2 Lys659-Ser674, and CKI buffer (40 mM Tris, 10 mM MgCl2, 0.5 mM DTT, 0.1 mg/ml BSA, pH 7.5); for CKIα, 1 ng/μl CKIα, 50 μM CKI peptide substrate, and CKI buffer; for CDK7, 5 ng/μl CDK7, 100 μM Cdk7/9 peptide substrate, and CKI buffer; for ERK2, 1.5 ng/μl ERK2, 0.8 μg/μl MBP, and ERK buffer (50 mM Tris, 10 mM MgCl2, 0.5 mM DTT, 1 mM EGTA, pH 7.5). Five hundred nl of compound was added to the mixture (final 5% DMSO), and the reaction was started by adding ATP (final 5 μM). After incubation at 30°C for 3h, 10 μl of Kinase-Glo Luminescent Kinase Assay reagent was added, and the luminescence was detected to determine the remaining ATP amount. All of the tested compounds did not inhibit luciferase activity directly [1]. |
| 動(dòng)物實(shí)驗(yàn) | MDA-MB-231 cells were injected s.c. into the right flank of nude mice (1×10^7 cells per mouse), and tumor growth was closely observed and measured every 3 days. When the tumors reached approximately 50 mm3, the mice were randomly divided into two groups (eight mice per group) and i.p. injected with the vehicle (0.8% DMSO/12% Cremophor/8% ethanol in normal saline) or 5 mg/kg longdaysin in vehicle every 3 days. This longdaysin dosage was selected based on results from preliminary experiments, and was well tolerated in the mouse model. Subsequently, tumor volumes were measured with a caliper and calculated as follows: 0.523×(length)×(width)2. After treatment for 3 weeks, the mice were sacrificed and the tumor tissues were collected and weighed before being fixed in buffered formalin [2]. |
| 體外活性 | Longdaysin對(duì)CKIδ、CKIα、ERK2和CDK7的活性產(chǎn)生了抑制作用（IC50分別為8.8、5.6、52和29 μM），而對(duì)p38α的影響則較小。CKIδ缺陷細(xì)胞的周期比野生型細(xì)胞長(zhǎng)1.1小時(shí)。在CKIδ缺陷細(xì)胞和野生型細(xì)胞中，Longdaysin以劑量依賴性方式延長(zhǎng)了周期[1]。在乳腺癌Hs578T和MDA-MB-231細(xì)胞中，micromolar濃度的Longdaysin減弱了LRP6和DVL2的磷酸化，并降低了活性β-catenin和總β-catenin的表達(dá)，從而導(dǎo)致Wnt靶基因Axin2、DKK1、LEF1和Survivin的下調(diào)[2]。 |
| 體內(nèi)活性 | 在MDA-MB-231乳腺癌異種移植模型中，longdaysin與Wnt/β-catenin信號(hào)傳導(dǎo)的抑制相關(guān)，抑制了腫瘤生長(zhǎng)[2]。 |
| 存儲(chǔ)條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | DMSO : 100 mg/mL (298.21 mM)
H2O : Insoluble
|
| 關(guān)鍵字 | ERK | Cyclin dependent kinase | inhibit | CDK | Inhibitor | Longdaysin | Casein Kinase | Extracellular signal regulated kinases |
| 相關(guān)產(chǎn)品 | Lidocaine hydrochloride | Astragaloside IV | Lidocaine | Sodium Oxamate | Honokiol | Ribociclib | Notoginsenoside R1 | CASIN | Tauroursodeoxycholate | Dinaciclib | TBHQ | Abemaciclib |
| 相關(guān)庫(kù) | 抑制劑庫(kù) | 經(jīng)典已知活性庫(kù) | 抗癌活性化合物庫(kù) | 已知活性化合物庫(kù) | 細(xì)胞周期化合物庫(kù) | 抗結(jié)直腸癌化合物庫(kù) | 激酶抑制劑庫(kù) | 抗衰老化合物庫(kù) | HIF-1化合物庫(kù) | 疼痛相關(guān)化合物庫(kù) |