TA-01_DataSheet_MedChemExpress

Inhibitors, Agonists, Screening Libraries Data SheetBIOLOGICAL ACTIVITY:T–5224 is a selective inhibitor of c–Fos/activator protein (AP)–1 for rheumatoid arthritis therapy, and inhibits MMP activity with IC 50s of 10 nM for both MMP–3 and MMP–13.IC50 & Target: IC50: 10 nM (MMP–3), 10 nM (MMP–13)In Vitro: T–5224 (0–80 μM) significantly inhibits the invasion, migration, and MMP activity of HSC–3–M3 cells in a dose–dependent manner. There is no significant influence on HSC–3–M3 amd OSC–19 cells proliferation [4].In Vivo: G2 is observed in rat and monkey liver microsomes as a major metabolite of T–5224, suggesting that G2 is not ahuman–specific metabolite [1]. T–5224 (300 mg/kg, p.o.) inhibits the production of TNF–alpha and other downstream effectors in C57BL/6 mice [2]. Administration of T–5224 (300 mg/kg, p.o.) after intraperitoneal injection of LPS impartes appreciable protectionagainst acute elevations in serum levels of TNFα, HMGB1, ALT/AST as well as in liver tissue levels of MIP–1α and MCP–1, and reduces the lethality (27%)[3]. PROTOCOL (Extracted from published papers and Only for reference)Cell Assay: T–5224 is dissolved in DMSO and diluted in DMEM.[4]HSC–3–M3 cells are starved for 24 h with DMEM containing 0.5%FBS. The top chamber of the cell invasion device is coated with 50 μL of 0.1 × basement membrane extract solution and incubataed overnight. HSC–3–M3 cells (5.0 × 104 cells/well) are added to the top chamber with DMEM containing 0.5% FBS mixed with 0–80 μMT–5224; DMEM with 10% FBS is added to the bottom chamber and incubated for 48 h. The bottom plate is read using a multilabel plate reader. The data are compared with the standard curve to determine the fraction of invaded cells.Animal Administration: T–5224 is dissolved in a polyvinylpyrrolidone solution, and adjusted to a concentration of 30 mg/mL.[2]Mice in LPS group are administered orally with polyvinylpyrrolidone solution in the same volume of T–5224 solution immediately after LPS injection, while in the T–5224 group, mice are administered orally with T–5224 (300 mg/kg, p.o.) in the same manner. In the control group, mice receives polyvinylpyrrolidone solution orally soon after intraperitoneal saline injection. Blood samples are collected for each measurement at the optimal time.References:[1]. Uchihashi S, et al. Metabolism of the c–Fos/activator protein–1 inhibitor T–5224 by multiple human UDP–glucuronosyltransferase isoforms. Drug Metab Dispos. 2011 May;39(5):803–13.[2]. Miyazaki H, et al. The effects of a selective inhibitor of c–Fos/activator protein–1 on endotoxin–induced acute kidney injury in mice. BMC Nephrol. 2012Nov 23;13:153.[3]. Izuta S, et al. T–5224, a selective inhibitor of c–Fos/activator protein–1, attenuates lipopolysaccharide–induced liver injury in mice. Biotechnol Lett. 2012Dec;34(12):2175–82.Product Name:T–5224Cat. No.:HY-12270CAS No.:530141-72-1Molecular Formula:C 29H 27NO 8Molecular Weight:517.53Target:MMP Pathway:Metabolic Enzyme/Protease Solubility:DMSO: ≥ 31 mg/mL[4]. Kamide D, et al. Selective activator protein–1 inhibitor T–5224 prevents lymph node metastasis in an oral cancer model. Cancer Sci. 2016 May; 107(5):666–73.Caution: Product has not been fully validated for medical applications. For research use only.Tel: 609-228-6898 Fax: 609-228-5909 E-mail: tech@Address: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USA。

Inhibitors, Agonists, Screening Libraries Data SheetBIOLOGICAL ACTIVITY:Tangeretin, a flavonoid from citrus fruit peels, has been proven to play an important role in anti–inflammatory responses and neuroprotective effects in several disease models, and was also selected as a Notch–1 inhibitor.IC50 value:Target: Notch–1In vitro: Tangeretin enhanced the radiosensitivity of GC cells as demonstrated by MTT and colony formation assays. Tangeretin also attenuated radiation–induced EMT, invasion and migration in GC cells, accompanied by a decrease in Notch–1, Jagged1/2, Hey–1 and Hes–1 expressions. Tangeretin triggered the upregulation of miR–410, a tumor–suppressive microRNA. Furthermore, re–expression of miR–410 prevented radiation–induced EMT and cell invasion [1].In vivo: In this study, we investigated the in vivo anti–RSV activity of tangeretin in 3–week–old male BALB/c mice. A plaque reduction assay and fluorescence quantitative polymerase chain reaction (FQ–PCR) showed that tangeretin inhibited RSV replication in the lung of mice [2].PROTOCOL (Extracted from published papers and Only for reference)Kinase assay [2]HEK293 cells (8 × 104 cells/well) were seeded in a 48–well plate and incubated for 24 h. Cells were transiently co–transfected with the pGL–NF–κB–luciferase reporter plasmid and the Renilla luciferase reporter plasmid pRL–TK using a Lipofectamine 3000 kit (Invitrogen,Carlsbad, CA). At 6 h following transfection, the cells were treated with varying concentrations of tangeretin and stimulated with RSV Long strain (MOI = 1) for 3, 6, 12, or 18 h. NF–κB luciferase activity was measured using the Dual–Luciferase Reporter Assay System (Promega, Madison, WI) using a microplate reader (Thermo, Rockford, IL) according to the instructions of the manufacturer. Data were expressed by dividing the firefly luciferase activity by the Renilla luciferase activity.Cell assay [2]The effect of tangeretin on RAW264.7 cells was determined using a MTT assay as previously reported.(13) Briefly, RAW264.7 cells (1 ×104 cells/well) were seeded in a 96–well plate for 24 h and treated with different concentrations of tangeretin (6.3–50.0 μM) anddimethyl sulfoxide (DMSO) (vehicle control, 0.01 and 0.1%) for 10 or 48 h. The absorbance was measured at 570 nm using an enzyme immunoassay (EIA) reader (Thermo Scientific, Waltham, MA), and cell viability (%) was calculated as follows: [(absorbance of the test group – absorbance of the blank control)/(absorbance of the control group – absorbance of the blank control)] × 100.Animal administration [2]The mice were maintained in an air–conditioned, pathogen–free room (temperature of 24 ± 2 °C, with a 12 h light/dark cycle from 6:00 am to 6:00 pm) with free access to food and water. Mice were randomly divided into five groups (n = 10) as follows: normal (control), RSV–challenged, and three treatment groups administered 25, 50, or 100 mg/kg/day tangeretin dissolved in saline. The control and RSV–challenged groups received equal volumes of saline. During the experiment, mice in the treatment groups wereProduct Name:Tangeretin Cat. No.:HY-N0133CAS No.:481-53-8Molecular Formula:C 20H 20O 7Molecular Weight:372.37Target:Notch Pathway:Stem Cell/Wnt Solubility:10 mM in DMSOintragastrically administrated tangeretin for 3 days consecutively before RSV stimulation. Mice were lightly anesthetized with diethyl ether and intranasally challenged with RSV Long strain [6.7 × 106 plaque–forming units (PFU)] on day 4 after tangeretin treatment, while the control group was sham–infected with an equal volume of HEp–2 cell lysate, which was centrifuged under the same conditions as the viral suspensions. The mice were weighed during the experiment and sacrificed on day 5 post–infection after anesthetizing them with chloral hydrate (Figure 1B). The lung tissues were removed and weighed, and the lung index was calculated using the following formula: lung index = lung weight/body weight.References:[1]. Zhang X, et al. Tangeretin enhances radiosensitivity and inhibits the radiation–induced epithelial–mesenchymal transition of gastric cancer cells. Oncol Rep. 2015 Jul;34(1):302–10.[2]. Xu JJ, et al. Tangeretin from Citrus reticulate Inhibits Respiratory Syncytial Virus Replication and Associated Inflammation in Vivo. J Agric Food Chem. 2015 Nov 4;63(43):9520–7.[3]. Hagenlocher Y, et al. Citrus peel polymethoxyflavones nobiletin and tangeretin suppress LPS– and IgE–mediated activation of human intestinal mast cells. Eur J Nutr. 2016 Mar 28.Caution: Product has not been fully validated for medical applications. For research use only.Tel: 609-228-6898 Fax: 609-228-5909 E-mail: tech@Address: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USA。

Inhibitors, Agonists, Screening Libraries Data SheetBIOLOGICAL ACTIVITY:D8–MMAE is a deuterated form of MMAE, which is a microtubule –disrupting agent.IC50 & Target: Microtubule [1]In Vitro: Antibody–drug conjugates (ADC) comprise targeting antibodies armed with potent small–molecule payloads. ADCs are generated to target different receptors on the anaplastic large cell lymphoma line L–82, but delivered the same cytotoxic payload (monomethyl auristatin E, MMAE), and the intracellular concentration of released MMAE correlated with in vitro ADC–mediated cytotoxicity independent of target expression or drug:antibody ratios. LC–MS is used to measure the concentration of MMAE in a parallel cohort of L–82 tumors with an identical treatment regimen. Although tumor volume is not different among treatment groups 3 days after dose, the intratumoral MMAE measurement reveals two patterns. First, intratumoral MMAE concentration increases proportionally to the ADC dose, which correspondes to stronger antitumor activity. Second, the intratumoral MMAEconcentration obtained from treatment with both cOKT9–vcMMAE and cAC10–vcMMAE is similar at each dose, consistent with the observation that tumor responded similarly to these two ADCs [1].In Vivo: Intratumoral MMAE concentrations consistently correlates with the extent of tumor growth inhibition in tumor xenograft models. IHC analysis reveals that nonbinding control–treated tumors consist of both CD30+ and CD30–cells, presumably because they do not kill either CD30+ or CD30– Karpas 299 cells. Only CD30– cells are found in cAC10–vcMMAF–treated tumors, illustrating that cAC10–vcMMAF eliminates most CD30+ cells. Interestingly, the two tumors that relapses from cAC10–vcMMAE treatment are also found to be CD30– by the end of study, indicating a small fraction of CD30– cells might have escaped from bystander killing in these two remaining tumors [1].PROTOCOL (Extracted from published papers and Only for reference)Kinase Assay:[1]Cell pellets are collected 24 hours after ADC treatment. Cell count, diameter, and circularity are determined on Vi–Cell Counter. MMAE extraction and quantification method is performed. Briefly, tumors or cell pellets are homogenized with methanol and acetonitrile containing internal standard (d 8–MMAE for MMAE detection and 13C–MMAF for MMAF detection).The homogenates are centrifuged at 10,000 rpm to precipitate protein and protein–bound payloads. The supernatant is then subjected to solid phase extraction, and signals of MMAE and MMAF are detected by LC–MS [1].References:[1]. Li F, et al. Intracellular Released Payload Influences Potency and Bystander–Killing Effects of Antibody–Drug Conjugates in Preclinical Models. Cancer Res.2016 May 1;76(9):2710–9.Product Name:D8–MMAE Cat. No.:HY-15162A CAS No.:2070009-72-0Molecular Formula:C 39H 59D 8N 5O 7Molecular Weight:726.03Target:Microtubule/Tubulin; Microtubule/Tubulin; ADC Cytotoxin Pathway:Cell Cycle/DNA Damage; Cytoskeleton; Antibody–drug Conjugate/ADC Related Solubility:DMSO: ≥ 40 mg/mLCaution: Product has not been fully validated for medical applications. For research use only.Tel: 609-228-6898 Fax: 609-228-5909 E-mail: tech@Address: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USA。

制备储备液
Mass Solvent Concentration
1 mM
1 mg 2.1585 mL
5 mg 10.7924 mL
10 mg 21.5848 mL
5 mM
0.4317 mL
2.1585 mL
4.3170 mL
10 mM
0.2158 mL
1.0792 mL
2.1585 mL
请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存方式和期限。
REFERENCES [1]. Zhang Y, et al. Autotaxin through lysophosphatidic acid stimulates polarization, motility, and transendothelial migration of naive T cells. J Immunol. 2012 Oct 15;189(8):3914-3924. [2]. Bai Z, et al. Constitutive lymphocyte transmigration across the basal lamina of high endothelial venules is regulated by theautotaxin/lysophosphatidic acid axis. J Immunol. 2013 Mar 1;190(5):2036-2048.
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