LY2228820 化学構造
分子量: 612.74

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製品説明

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    p38 MAPK製品生物活性の比較
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製品の説明

生物活性

製品説明 LY2228820は、p38 MAPKの新しくて強力な阻害剤で、 IC50 が7 nMになる。
ターゲット p38α
IC50 7 nM [1]
In vitro試験 LY2228820 inhibits p38α, as well as the level of phosphoMAPKAPK-2 (pMK2) in RAW 264.7 cells, with IC50 values of 7 nM and 34.3 nM, respectively. Furthermore, LY2228820 inhibits lipopolysaccharide (LPS)-induced TNFα formation in murine peritoneal macrophages, with IC50 of 5.2 nM. [1] In multiple myeloma (MM) cells, including INA6, RPMI-8226, U266, and RPMI-Dox40, LY2228820 (200 nM–800 nM) significantly blocks p38MAPK signaling, as revealed by its inhibition on phosphorylation of HSP27, a downstream target of p38MAPK, without affecting the expression level of HSP27. LY2228820 (200 nM–400 nM) enhances bortezomib-induced cytotoxicity and apoptosis, but LY2228820 alone doesn't inhibit the growth of MM.1S cells. LY2228820 (200 nM–800 nM) also inhibits secretion of IL-6 and MIP-1α in long-term BM stromal cells (LT-BMSCs), BM mononuclear cells (BMMNCs), peripheral blood (PB) CD138+, CD138 or PB CD14+ cells. LY2228820 (400 nM–800 nM) also blocks osteoclastogenesis from CD14+ cells. [2]
Cell Data
Cell LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
RPMI-8226 M1z3[GtqdmG|ZTDhd5NigQ>? MV;+PFAxKG6P M2PqfmROW09? NX;yOI17cW6qaXLpeJMheGixc4Doc5J6dGG2aX;uJI9nKEiVUEK3 MonxNVg{QTd|NEW=
U266 MoTOT4lv[XOnIHHzd4F6 NH7N[Gh,QDByIH7N NUTRWoVJTE2VTx?= Mn[0bY5pcWKrdIOgdIhwe3Cqb4L5cIF1cW:wIH;mJGhUWDJ5 NF3GUWYyQDN7N{O0OS=>
MM.1S MoXET4lv[XOnIHHzd4F6 M37PRZ45ODBibl2= NWPEemJvTE2VTx?= MnXQbY5pcWKrdIOgdIhwe3Cqb4L5cIF1cW:wIH;mJGhUWDJ5 NYPq[WtWOTh|OUezOFU>
RPMI-Dox40 MkO5T4lv[XOnIHHzd4F6 MnO5glgxOCCwTR?= Mnr2SG1UVw>? NHnnU2ZqdmirYnn0d{BxcG:|cHjvdplt[XSrb36gc4YhUFOSMke= NYG1bY5kOTh|OUezOFU>
RPMI-LR5 NFPuNndMcW6jc3WgZZN{[Xl? M2DsVp45ODBibl2= NH[z[GNFVVOR M3TwUolvcGmkaYTzJJBpd3OyaH;yfYxifGmxbjDv[kBJW1B{Nx?= MnHrNVg{QTd|NEW=
INA-6 MoLIT4lv[XOnIHHzd4F6 NWeyZ45NhjhyMDDuUS=> MlL2SG1UVw>? NIHyUolqdmirYnn0d{BxcG:|cHjvdplt[XSrb36gc4YhUFOSMke= Mni3NVg{QTd|NEW=
RPMI-8226 MlXHR5l1d3irY3n0fUBie3OjeR?= MVX+NVAxOCCwTR?= M3vUOWROW09? NEK0TlZvdyC|aXfubYZq[2GwdDDjfZRwfG:6aXPpeJk> MV:xPFM6PzN2NR?=
U266 MlvIR5l1d3irY3n0fUBie3OjeR?= MofzglExODBibl2= MmPwSG1UVw>? Mnflco8he2mpbnnmbYNidnRiY4n0c5RwgGmlaYT5 MWKxPFM6PzN2NR?=
MM.1S NFjyVGJEgXSxeHnjbZR6KGG|c3H5 MX\+NVAxOCCwTR?= NHn6dnlFVVOR M4S1Zo5wKHOrZ37p[olk[W62IHP5eI91d3irY3n0fS=> NISzTmkyQDN7N{O0OS=>
RPMI-Dox40 MWXDfZRwgGmlaYT5JIF{e2G7 NG\MOI1,OTByMDDuUS=> MX;EUXNQ MWfuc{B{cWewaX\pZ4FvfCCleYTveI95cWOrdIm= MX6xPFM6PzN2NR?=
RPMI-LR5 M{fQVGN6fG:6aXPpeJkh[XO|YYm= MnXDglExODBibl2= MmrrSG1UVw>? M2LH[Y5wKHOrZ37p[olk[W62IHP5eI91d3irY3n0fS=> Mlf0NVg{QTd|NEW=
INA-6 M2e4e2N6fG:6aXPpeJkh[XO|YYm= MWX+NVAxOCCwTR?= MUPEUXNQ MXPuc{B{cWewaX\pZ4FvfCCleYTveI95cWOrdIm= MVSxPFM6PzN2NR?=
CD14+ MkLISpVv[3Srb36gZZN{[Xl? M3[5R545ODBibl2= MlXGSG1UVw>? MlvObY5pcWKrdIOgc5N1\W:lbHHzeI9o\W6nc3nzJIZzd21iQ1SxOEBxd3OrdHn2[UBk\Wyucx?= MW[xPFM6PzN2NR?=
U-87-MG NXPTV5Q2TnWwY4Tpc44h[XO|YYm= NHXmRWEyKM7:TR?= NICwTpVFVVOR NYPhVZI5emWmdXPld{B1fW2xcj3kdol3\W5iY3;y[EBnd3KvYYTpc44> MoDtNlM{OzV3ME[=
MDA-MB-231 NHvCcIVHfW6ldHnvckBie3OjeR?= NHLhVG4yKM7:TR?= MV3EUXNQ MnLldoVlfWOnczD0eY1wei2mcnn2[Y4h[2:{ZDDmc5Ju[XSrb36= MWiyN|M{PTVyNh?=
A-2780 M4PwZmZ2dmO2aX;uJIF{e2G7 NYXiOGZHOSEQvF2= NFrESVRFVVOR NEXJWW1z\WS3Y3XzJJR2dW:{LXTybZZmdiClb4LkJIZwem2jdHnvci=> MWqyN|M{PTVyNh?=
SK-OV-3 MX7GeY5kfGmxbjDhd5NigQ>? NXn3NnNmOSEQvF2= MnLqSG1UVw>? MVzy[YR2[2W|IIT1cY9zNWS{aY\lckBkd3KmIH\vdo1ifGmxbh?= MkiyNlM{OzV3ME[=
LXFA-629 M1\5TmZ2dmO2aX;uJIF{e2G7 NHS3WYUyKM7:TR?= NGXSe5BFVVOR MUny[YR2[2W|IIT1cY9zNWS{aY\lckBkd3KmIH\vdo1ifGmxbh?= M3fqUVI{OzN3NUC2
NCI-H1650 NIraT4RHfW6ldHnvckBie3OjeR?= NEnRdVYyKM7:TR?= M3TweWROW09? NFyxNFRz\WS3Y3XzJJR2dW:{LXTybZZmdiClb4LkJIZwem2jdHnvci=> NXrqeppFOjN|M{W1NFY>
PC-3 MnS5SpVv[3Srb36gZZN{[Xl? MoDWNUDPxE1? NYG5b5pPTE2VTx?= NHnDTFJz\WS3Y3XzJJR2dW:{LXTybZZmdiClb4LkJIZwem2jdHnvci=> NFzHdmYzOzN|NUWwOi=>
RAW264.7 MUfGeY5kfGmxbjDhd5NigQ>? Mn7EglIxKM7:TR?= NInNRVFFVVOR Mkn5bY5pcWKrdIOgRY5qe2:veXPpck1{fGmvdXzheIVlKE2NMjDwbI9{eGixconsZZRqd25id3n0bEBKSzVyIH;mJFM2NjNibl2= MWqyOFM2PjhzNB?=
mouse peritoneal macrophages NE\sXlVHfW6ldHnvckBie3OjeR?= M1GxVZ4zOCEQvF2= MVzEUXNQ M3fmUWxRWy:LRl6t{tPjiJO|dHnteYxifGWmIGTOSk3PuSCycn;keYN1cW:wIIfpeIghUUN3MDDv[kA3NjNibl2= NHHrWI4zPDN3NkixOC=>
A549 NGrsVVVHfW6ldHnvckBie3OjeR?= MkLOglIxKM7:TR?= M4HFUmROW09? NXjCZpZLcW6qaXLpeJMhVFCVLXnu[JVk\WRiQ2jDUFgheHKxZIXjeIlwdiC5aYToJGlEPTBib3[gNVQ1Njlibl2= NIKwR44zPDN3NkixOC=>
MDA-231 NF;t[5NHfW6ldHnvckBie3OjeR?= MW\+NVAh|ryP MWfzeZBxemW|c3XzJGRMUy1zIHX4dJJme3Orb36= NUHwRnhYOjZ2MEe4OFM>
MCF-7 MoLFSpVv[3Srb36gZZN{[Xl? M1;udJ4yOCEQvF2= MYrzeZBxemW|c3XzJGRMUy1zIHX4dJJme3Orb36= MVqyOlQxPzh2Mx?=
MDA-435 M{G1fGZ2dmO2aX;uJIF{e2G7 NV6yNW51hjFyIN88US=> NVr3bFBWe3WycILld5NmeyCGS1utNUBmgHC{ZYPzbY9v M2X1XlI3PDB5OESz
PC3 MYfGeY5kfGmxbjDhd5NigQ>? NH\6NFJ,OTBizszN MmXRSG1UVw>? MlnMd5VxeHKnc4Pld{BFU0tvMTDlfJBz\XO|aX;u NYPue2dPOjZ7MUO2NFg>

... Click to View More Cell Line Experimental Data

In vivo試験 In LPS-induced mice, LY2228820 effectively inhibits the formation of TNFα with a threshold minimum 50% effective dose (TMED50) less than 1 mg/kg. In a rat model of collagen-inducedarthritis (CIA), LY2228820 displays potent effects on paw swelling, bone erosion, and cartilage destruction, with a threshold minimum 50% effective dose (TMED50)of 1.5 mg/kg. [1]
臨床試験 LY2228820 is currently under a Phase I clinical trial for the treatment of advanced cancer.
特集

プロトコル (参考用のみ)

キナーゼアッセイ: [1]

Inhibition of p38α Inhibition of p38α is determined using recombinant human p38α in a standard filter binding protocol using ATP[γ-33P] and EGFR 21-mer peptide as substrate. Functional inhibition of TNFα in murine peritoneal macrophages is determined using LPS stimulation in the presence of LY2228820. To assess p38α activity in cells more directly, RAW 264.7 cells are treated with LY2228820 and then stimulated with anisomycin. The level of p38α activity is detected using a phosphoMAPKAPK-2 (pMK2) (Thr 334) antibody which reacts with a residue specifically phosphorylated by p38α.

細胞アッセイ: [2, 3]

細胞株 MM cells, including INA6, RPMI-8226, U266, and RPMI-Dox40
濃度 200 nM–800 nM
反応時間 48 hours
実験の流れ MTT assays and APO 2.7 staining are performed to assess cellular proliferation and induction of apoptosis, respectively. Viability is expressed as percent viable cells. Apoptosis in cells is evaluated by APO 2.7 staining. For detection of mitochondrial membrane protein 7A6 expressed in apoptotic cells, cells are incubated with APO 2.7 reagent for 20 min. Expression of APO 2.7 is determined using an EPICS XL flow cytometer.

動物実験: [1]

動物モデル Lipopolysaccharide (LPS)-induced Balb/c mice
製剤 Dissolved in 1% CMC/0.25% Tween 80 in water
投薬量 0–20 mg/kg
投与方法 Oral bid dosing for 14 days

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDogMonkeyBaboon
Weight (kg)0.020.151.80.40.0810312
Body Surface Area (m2)0.0070.0250.150.050.020.50.240.6
Km factor361285201220
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

参考

化学情報

Download LY2228820 SDF
分子量 612.74
化学式

C24H29FN6.2CH4O3S

CAS No. 862507-23-1
保管 3年-20℃
2年-80℃in solvent
別名 N/A
溶解度 (25°C) * In vitro Water 100 mg/mL warming (163.2 mM)
DMSO 4 mg/mL warming (6.52 mM)
Ethanol 3 mg/mL (4.89 mM)
In vivo Saline 30 mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
化学名 5-(2-tert-butyl-4-(4-fluorophenyl)-1H-imidazol-5-yl)-3-neopentyl-3H-imidazo[4,5-b]pyridin-2-amine dimethanesulfonate

文献中の引用 (9)

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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