Otenabant_DataSheet_MedChemExpress

Inhibitors, Agonists, Screening Libraries Data SheetBIOLOGICAL ACTIVITY:YM–58483 is the first selective and potent inhibitor of CRAC channels and subsequent Ca 2+ signals.In Vitro: YM–58483 can decrease the levels of P–ERK and P–CREB, without affecting the expression of CD11b andGFAP. YM–58483 also inhibits the release of spinal cord IL–1β, TNF–α, and PGE2[1]. YM–58483 and cyclosporine A inhibits T cell proliferation in a one–way mixed lymphocyte reaction (mLR) with IC 50 values of 330 and 12.7 nM, respectively [2]. YM–58483 inhibits DNP antigen–induced histamine release from and leukotrienes (LTs) production in IgE–primed RBL–2H3 cells, a rat basophilic leukemia cell line, with IC 50 values of 460 and 310 nM, respectively. YM–58483 also inhibits phytohemagglutinin–P (PHA)–stimulated IL–5 and IL–13 production in human peripheral blood cells with IC 50 values of 125 and 148 nM, respectively, which is approximately 5 times less potent than prednisolone [3]. YM–58483 inhibits IL–4 and IL–5 production in a conalbumine–stimulated murine Th2 T cellclone (D10.G4.1), and IL–5 production in phytohemagglutinin–stimulated human whole blood cells with IC 50 values comparable to those reported for its CRAC channel inhibition (around 100 nM)[4].In Vivo: Intrathecal YM–58483 at the concentration of 300 μM (1.5 nmol) and 1000 μM (10 nmol) produces a significant central analgesic effect on the SNL rats [1]. In the mouse graft–versus–host disease (GVHD) model, YM–58483 (1–30 mg/kg, p.o.) and cyclosporine A (1–30 mg/kg, p.o.) inhibit donor anti–host cytotoxic T lymphocyte (CTL) activity and IFN–γ production, and also reduce the number of donor T cells, especially donor CD8+ T cells, in the spleen. YM–58483 (1–10 mg/kg, p.o.) and cyclosporine A (2, 10 mg/kg, p.o.) inhibit the sheep red blood cell (SRBC)–induced delayed type hypersensitivity (DTH) response [2]. M–58483 (30mg/kg, p.o.) significantly suppresses ovalbumin (OVA)–induced bronchoconstriction in OVA–sensitized guinea pigs, whereas prednisolone does not. YM–58483 (3–30 mg/kg, p.o.) and prednisolone (100 mg/kg, p.o.) both significantly and completelysuppress airway hyperresponsiveness (AHR) caused by OVA exposure [3]. YM–58483 inhibits antigen–induced eosinophil infiltration into airways, and decreases IL–4 and cysteinyl–leukotrienes content in inflammatory airways induced in actively sensitized Brown Norway rats. Orally administered YM–58483 prevents antigen–induced late phase asthmatic broncoconstriction and eosinophil infiltration in actively sensitized guinea pigs [4].PROTOCOL (Extracted from published papers and Only for reference)Animal Administration: YM–58483 is suspended in 0.5% methylcellulose solution for oral administration at a volume of 10mL/kg.[2]Male Balb/c mice are immunized by subcutaneous injection of SRBC (2×107 cells) on day 0. Immunized mice are challenged with 30 μL of 1×108 SRBC into the left hind footpad on day 5. Footpad swelling is measured 24 h after the challenge using a thickness gauge and expressed as the difference between the thickness of the left footpad and that of the right one, which receives an equal volume of 0.9% saline. As a negative control, male Balb/c mice are injected with 0.9% saline and challenged with SRBC. YM–58483 and cyclosporine A are administered orally once daily from day 0 to day 5 (6 consecutive days).Product Name:YM–58483Cat. No.:HY-100831CAS No.:223499-30-7Molecular Formula:C 15H 9F 6N 5OS Molecular Weight:421.32Target:CRAC Channel Pathway:Membrane Transporter/Ion Channel Solubility:DMSO: ≥ 32 mg/mLReferences:[1]. Qi Z, et al. The Central Analgesic Mechanism of YM–58483 in Attenuating Neuropathic Pain in Rats. Cell Mol Neurobiol. 2016 Oct;36(7):1035–43.[2]. Ohga K, et al. Characterization of YM–58483/BTP2, a novel store–operated Ca2+ entry blocker, on T cell–mediated immune responses in vivo. Int Immunopharmacol. 2008 Dec 20;8(13–14):1787–92[3]. Ohga K, et al. The suppressive effects of YM–58483/BTP–2, a store–operated Ca2+ entry blocker, on inflammatory mediator release in vitro and airway responses in vivo. Pulm Pharmacol Ther. 2008;21(2):360–9.[4]. Yoshino T, et al. YM–58483, a selective CRAC channel inhibitor, prevents antigen–induced airway eosinophilia and late phase asthmatic responses via Th2 cytokine inhibition in animal models. Eur J Pharmacol. 2007 Apr 10;560(2–3):225–33.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:PF 1022A is a N–methylated cyclooctadepsipeptides (CODPs) with strong anthelmintic properties; acts as an ionophore.IC50 value:Target:PF 1022A showed strong anthelmintic activities against Ascaridia galli in chickens [1]. PF1022A is a novel anthelmintic that binds to the latrophilin–like transmembrane receptor important for pharyngeal pumping in nematodes. Furthermore, PF1022A binds to GABA receptors, which might contribute to the anthelmintic effect. Like other cyclodepsipeptides, PF1022A acts as an ionophore [2]. In vitro, PF1022A showed low activity on embryonation but significantly inhibited egg hatch (10 and 100 μg/ml), whereas albendazole (10 and 100 μg/ml) revealed statistically significant inhibitions of both embryonation and egg hatch. PF1022A (1–100 μg/ml)completely inhibited larval movement at most examination points [3].References:[1]. Sasaki T, et al. A new anthelmintic cyclodepsipeptide, PF1022A. J Antibiot (Tokyo). 1992 May;45(5):692–7.[2]. Dornetshuber R, et al. Effects of the anthelmintic drug PF1022A on mammalian tissue and cells. Biochem Pharmacol. 2009 Apr 15;77(8):1437–44.[3]. Nwosu U, et al. Efficacy of the cyclooctadepsipeptide PF1022A against Heligmosomoides bakeri in vitro and in vivo. Parasitology. 2011 Aug;138(9):1193–201.Product Name:PF 1022A Cat. No.:HY-12361CAS No.:133413-70-4Molecular Formula:C 52H 76N 4O 12Molecular Weight:949.18Target:Parasite Pathway:Anti–infection Solubility:DMSO: ≥ 43 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。

Inhibitors, Agonists, Screening Libraries Data SheetBIOLOGICAL ACTIVITY:LY3009120 is a pan RAF and RAF dimer inhibitor, and inhibits BRAF V600E , BRAF WT and CRAF WT with IC 50 values of 5.8, 9.1 and 15 nM,respectively.IC50 & Target: IC50: 5.8 nM (BRAF V600E ), 9.1 nM (BRAF WT ), 15 nM (CRAF WT )[1]In Vitro: In the whole–cell based KiNativ assay, LY3009120 shows affinity to each RAF isoform with the IC 50 of 44, 31–47 and 42nM for ARAF, BRAF and CRAF respectively. LY3009120 exhibits anti–proliferative effects on cell lines harboring BRAF V600E , KRAS G13and KRAS G12 mutations. LY3009120 (1 μM) inhibits the phosphorylation of both MEK1/2 and ERK1/2 in cell lines with high basal levels of pMEK1/2 and pERK1/2 (RKO and HCT 116)[1]. LY3009120 shows inhibitory effect on tumor cells such as BxPC–3, NCI–H2405and OV–90 cell lines. LY3009120 (0.01 μM) demonstrates potent and dose–dependent inhibition of phospho–MEK and ERK in all three cell lines. LY3009120 demonstrates a concentration–dependent cell growth inhibition with IC 50 values of 0.04, 0.087, and 0.007 μM against H2405, BxPC–3, and OV–90 cells, respectively [2]. LY3009120 inhibits BRAF WT , CRAF WT , BRAF V600E , andBRAF V600E+G468A with the IC 50 values of 9.1, 15, 5.8, and 17 nM, respectively. LY3009120 induces BRAF–CRAF dimerization but inhibits the phosphorylation of downstream MEK and ERK. LY3009120 also inhibits various forms of RAF dimers including BRAF or CRAF homodimers [3]. LY3009120 gives only very minor activation at very low doses, with near complete inhibition of phospho–ERKat concentrations above 100 nM [4].In Vivo: LY3009120 (20 mg/kg bid) displays significant activity in in vivo BRAF mut and KRAS mut CRC xenograft models. In Colo 205xenografts (BRAF mut ), LY3009120 results in statistically significant tumor regression, while treatment of HCT 116 xenografts (KRAS mut ) results in statistically significant inhibition of tumor growth. LY3009120 treatment reduces pMEK1/2 in all HT–29 xenografts and reduces pERK1/2 in the majority of HT–29 xenografts [1]. LY3009120 (15 or 30 mg/kg) achieves almost complete tumor growth regression, and inhibits downstream phospho–MEK and ERK by approximately 70% and 60%, respectively, in the H2405 model [2]. PROTOCOL (Extracted from published papers and Only for reference)Kinase Assay:[3]In the BRAF WT enzymatic assay, the reaction mixture contains 1.2 nM BRAF, 30 nM MEK1, 1000 μM ATP, 3.5units (per 100 μL) of PK, 5 units (per 100 μL) of LDH, 1 mM PEP, and 280 μM of NADH. In the CRAF assay, the reaction mixture contains 0.6 nM CRAF, 26 nM MEK1, 2000 μM ATP, and the same amount of PK, LDH, PEP and NADH. In the BRAF V600E assay,the reaction mixture contains 1.6 μM BRAF V600E , 26 nM MEK1, 200 μM ATP and the same amount of PK, LDH, PEP andNADH as above. In the BRAF V600E+G468A assay, the reaction mixture contains 3.5 nM BRAF, 30 nM MEK1, 200 μM ATP and the same amount of PK, LDH, PEP and NADH as above. All assays are started by mixing the above mixture with test compound and monitored at A340 continuously for approximately 5 hr. Reaction data at the 3 to 4 hour time frame are collected to calculate IC 50.Cell Assay:[4]Briefly, cells are grown in McCoy’s 5A supplemented with 10% characterized fetal bovine serum and 1%penicillin/streptomycin/l–glutamine at 37°C, 5% CO 2, and 95% humidity. Cells are allowed to expand until 75–90% confluency at which point they are subcultured or harvested for assay use. A serial dilution of test compound is dispensed into a 384–well blackProduct Name:LY3009120Cat. No.:HY-12558CAS No.:1454682-72-4Molecular Formula:C 23H 29FN 6O Molecular Weight:424.51Target:Raf; Autophagy Pathway:MAPK/ERK Pathway; Autophagy Solubility:DMSO: ≥ 38 mg/mLclear bottom plate in triplicate. Six–hundred–twenty–five cells are added per well in 50 μL of complete growth medium in the384–well plate. Plates are incubated for 67 h at 37°C, 5% CO2, and 95% humidity. At the end of the incubation period, 10 μL of a 440μM solution of resazurin in PBS is added to each well of the plate and plates are incubated for an additional 5 h at 37°C, 5% CO2, and 95% humidity. Plates are read on a Synergy2 reader using an excitation of 540 nm and an emission of 600 nm. Data are analyzed using Prism softwareto calculate IC50 values.Animal Administration:[2]Briefly, 5×106 to 10×106 tumor cells in a 1:1 Matrigel mix (0.2 mL total volume) are injected subcutaneously into the right hind flank of female NIH nude rats. After tumors reach a desired size of approximately 300 mm3, animals are randomized into groups of 8 for efficacy studies. Drugs (LY3009120 or vemurafenib) are administered orally (gavage) in 0.6–mL volume of vehicle with the dose schedules. Tumor growth and body weight are monitored over time to evaluate efficacy and signs of toxicity.References:[1]. Vakana E, et al. LY3009120, a panRAF inhibitor, has significant anti–tumor activity in BRAF and KRAS mutant preclinical models of colorectal cancer. Oncotarget. 2017 Feb 7;8(6):9251–9266.[2]. Chen SH, et al. Oncogenic BRAF Deletions That Function as Homodimers and Are Sensitive to Inhibition by RAF Dimer Inhibitor LY3009120. Cancer Discov. 2016 Mar;6(3):300–15.[3]. Peng SB, et al. Inhibition of RAF Isoforms and Active Dimers by LY3009120 Leads to Anti–tumor Activities in RAS or BRAF Mutant Cancers. Cancer Cell. 2015 Sep 14;28(3):384–98.[4]. Henry JR, et al. Discovery of 1–(3,3–dimethylbutyl)–3–(2–fluoro–4–methyl–5–(7–methyl–2–(methylamino)pyrido[2,3–d]pyrimidin–6–yl)phenyl)urea (LY3009120) as a pan–RAF inhibitor with minimal paradoxical activation and activity against BRAF or RAS mutant tumoCaution: 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 LibrariesSafety Data Sheet Revision Date:Jun.-20-2017Print Date:Jun.-20-20171. PRODUCT AND COMPANY IDENTIFICATION1.1 Product identifierProduct name :AT-406Catalog No. :HY-15454CAS No. :1071992-99-81.2 Relevant identified uses of the substance or mixture and uses advised againstIdentified uses :Laboratory chemicals, manufacture of substances.1.3 Details of the supplier of the safety data sheetCompany:MedChemExpress USATel:609-228-6898Fax:609-228-5909E-mail:sales@1.4 Emergency telephone numberEmergency Phone #:609-228-68982. HAZARDS IDENTIFICATION2.1 Classification of the substance or mixtureGHS Classification in accordance with 29 CFR 1910 (OSHA HCS)Acute toxicity, Oral (Category 4), H302Acute aquatic toxicity (Category 1), H400Chronic aquatic toxicity (Category 1), H4102.2 GHS Label elements, including precautionary statementsPictogramSignal word WarningHazard statement(s)H302 Harmful if swallowed.H410 Very toxic to aquatic life with long lasting effects.Precautionary statement(s)P264 Wash skin thoroughly after handling.P270 Do not eat, drink or smoke when using this product.P273 Avoid release to the environment.P301 + P312 IF SWALLOWED: Call a POISON CENTER or doctor/ physician if you feel unwell.P330 Rinse mouth.P391 Collect spillage.P501 Dispose of contents/ container to an approved waste disposal plant.2.3 Other hazardsNone.3. COMPOSITION/INFORMATION ON INGREDIENTS3.1 SubstancesSynonyms:SM–406; Debio–1143Formula:C32H43N5O4Molecular Weight:561.71CAS No. :1071992-99-84. FIRST AID MEASURES4.1 Description of first aid measuresEye contactRemove any contact lenses, locate eye-wash station, and flush eyes immediately with large amounts of water. Separate eyelids with fingers to ensure adequate flushing. Promptly call a physician.Skin contactRinse skin thoroughly with large amounts of water. Remove contaminated clothing and shoes and call a physician.InhalationImmediately relocate self or casualty to fresh air. If breathing is difficult, give cardiopulmonary resuscitation (CPR). Avoid mouth-to-mouth resuscitation.IngestionWash out mouth with water; Do NOT induce vomiting; call a physician.4.2 Most important symptoms and effects, both acute and delayedThe most important known symptoms and effects are described in the labelling (see section 2.2).4.3 Indication of any immediate medical attention and special treatment neededTreat symptomatically.5. FIRE FIGHTING MEASURES5.1 Extinguishing mediaSuitable extinguishing mediaUse water spray, dry chemical, foam, and carbon dioxide fire extinguisher.5.2 Special hazards arising from the substance or mixtureDuring combustion, may emit irritant fumes.5.3 Advice for firefightersWear self-contained breathing apparatus and protective clothing.6. ACCIDENTAL RELEASE MEASURES6.1 Personal precautions, protective equipment and emergency proceduresUse full personal protective equipment. Avoid breathing vapors, mist, dust or gas. Ensure adequate ventilation. Evacuate personnel to safe areas.Refer to protective measures listed in sections 8.6.2 Environmental precautionsTry to prevent further leakage or spillage. Keep the product away from drains or water courses.6.3 Methods and materials for containment and cleaning upAbsorb solutions with finely-powdered liquid-binding material (diatomite, universal binders); Decontaminate surfaces and equipment by scrubbing with alcohol; Dispose of contaminated material according to Section 13.7. HANDLING AND STORAGE7.1 Precautions for safe handlingAvoid inhalation, contact with eyes and skin. Avoid dust and aerosol formation. Use only in areas with appropriate exhaust ventilation.7.2 Conditions for safe storage, including any incompatibilitiesKeep container tightly sealed in cool, well-ventilated area. Keep away from direct sunlight and sources of ignition.Recommended storage temperature:Powder-20°C 3 years4°C 2 yearsIn solvent-80°C 6 months-20°C 1 monthShipping at room temperature if less than 2 weeks.7.3 Specific end use(s)No data available.8. EXPOSURE CONTROLS/PERSONAL PROTECTION8.1 Control parametersComponents with workplace control parametersThis product contains no substances with occupational exposure limit values.8.2 Exposure controlsEngineering controlsEnsure adequate ventilation. Provide accessible safety shower and eye wash station.Personal protective equipmentEye protection Safety goggles with side-shields.Hand protection Protective gloves.Skin and body protection Impervious clothing.Respiratory protection Suitable respirator.Environmental exposure controls Keep the product away from drains, water courses or the soil. Cleanspillages in a safe way as soon as possible.9. PHYSICAL AND CHEMICAL PROPERTIES9.1 Information on basic physical and chemical propertiesAppearance White to off-white (Solid)Odor No data availableOdor threshold No data availablepH No data availableMelting/freezing point No data availableBoiling point/range No data availableFlash point No data availableEvaporation rate No data availableFlammability (solid, gas)No data availableUpper/lower flammability or explosive limits No data availableVapor pressure No data availableVapor density No data availableRelative density No data availableWater Solubility No data availablePartition coefficient No data availableAuto-ignition temperature No data availableDecomposition temperature No data availableViscosity No data availableExplosive properties No data availableOxidizing properties No data available9.2 Other safety informationNo data available.10. STABILITY AND REACTIVITY10.1 ReactivityNo data available.10.2 Chemical stabilityStable under recommended storage conditions.10.3 Possibility of hazardous reactionsNo data available.10.4 Conditions to avoidNo data available.10.5 Incompatible materialsStrong acids/alkalis, strong oxidising/reducing agents.10.6 Hazardous decomposition productsUnder fire conditions, may decompose and emit toxic fumes.Other decomposition products - no data available.11.TOXICOLOGICAL INFORMATION11.1 Information on toxicological effectsAcute toxicityClassified based on available data. For more details, see section 2Skin corrosion/irritationClassified based on available data. For more details, see section 2Serious eye damage/irritationClassified based on available data. For more details, see section 2Respiratory or skin sensitizationClassified based on available data. For more details, see section 2Germ cell mutagenicityClassified based on available data. For more details, see section 2CarcinogenicityIARC: No component of this product present at a level equal to or greater than 0.1% is identified as probable, possible or confirmed human carcinogen by IARC.ACGIH: No component of this product present at a level equal to or greater than 0.1% is identified as a potential or confirmed carcinogen by ACGIH.NTP: No component of this product present at a level equal to or greater than 0.1% is identified as a anticipated or confirmed carcinogen by NTP.OSHA: No component of this product present at a level equal to or greater than 0.1% is identified as a potential or confirmed carcinogen by OSHA.Reproductive toxicityClassified based on available data. For more details, see section 2Specific target organ toxicity - single exposureClassified based on available data. For more details, see section 2Specific target organ toxicity - repeated exposureClassified based on available data. For more details, see section 2Aspiration hazardClassified based on available data. For more details, see section 212. ECOLOGICAL INFORMATION12.1 ToxicityNo data available.12.2 Persistence and degradabilityNo data available.12.3 Bioaccumlative potentialNo data available.12.4 Mobility in soilNo data available.12.5 Results of PBT and vPvB assessmentPBT/vPvB assessment unavailable as chemical safety assessment not required or not conducted.12.6 Other adverse effectsNo data available.13. DISPOSAL CONSIDERATIONS13.1 Waste treatment methodsProductDispose substance in accordance with prevailing country, federal, state and local regulations.Contaminated packagingConduct recycling or disposal in accordance with prevailing country, federal, state and local regulations.14. TRANSPORT INFORMATIONDOT (US)This substance is considered to be non-hazardous for transport.IMDGUN number: 3077Class: 9Packing group: IIIEMS-No: F-A, S-FProper shipping name: ENVIRONMENTALLY HAZARDOUS SUBSTANCE, SOLID, N.O.S.Marine pollutant: Marine pollutantIATAUN number: 3077Class: 9Packing group: IIIProper shipping name: Environmentally hazardous substance, solid, n.o.s.15. REGULATORY INFORMATIONSARA 302 Components:No chemicals in this material are subject to the reporting requirements of SARA Title III, Section 302.SARA 313 Components:This material does not contain any chemical components with known CAS numbers that exceed the threshold (De Minimis) reporting levels established by SARA Title III, Section 313.SARA 311/312 Hazards:No SARA Hazards.Massachusetts Right To Know Components:No components are subject to the Massachusetts Right to Know Act.Pennsylvania Right To Know Components:No components are subject to the Pennsylvania Right to Know Act.New Jersey Right To Know Components:No components are subject to the New Jersey Right to Know Act.California Prop. 65 Components:This product does not contain any chemicals known to State of California to cause cancer, birth defects, or anyother reproductive harm.16. OTHER INFORMATIONCopyright 2017 MedChemExpress. The above information is correct to the best of our present knowledge but does not purport to be all inclusive and should be used only as a guide. The product is for research use only and for experienced personnel. It must only be handled by suitably qualified experienced scientists in appropriately equipped and authorized facilities. The burden of safe use of this material rests entirely with the user. MedChemExpress disclaims all liability for any damage resulting from handling or from contact with this product.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。