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
  • 研究分野

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 MXjLbY5ie2ViYYPzZZk> NVvHXpFkhjhyMDDuUS=> NG\jSYpFVVOR MULpcohq[mm2czDwbI9{eGixconsZZRqd25ib3[gTHNROjd? NUHNblZFOTh|OUezOFU>
U266 MWnLbY5ie2ViYYPzZZk> M4\VUp45ODBibl2= MXTEUXNQ NI\SR3RqdmirYnn0d{BxcG:|cHjvdplt[XSrb36gc4YhUFOSMke= MUWxPFM6PzN2NR?=
MM.1S NWjUUoh5U2mwYYPlJIF{e2G7 NIn4XWx,QDByIH7N MVvEUXNQ MWfpcohq[mm2czDwbI9{eGixconsZZRqd25ib3[gTHNROjd? NU[xVHo{OTh|OUezOFU>
RPMI-Dox40 MUDLbY5ie2ViYYPzZZk> NU\z[3F2hjhyMDDuUS=> NW\5TWpOTE2VTx?= M4jifIlvcGmkaYTzJJBpd3OyaH;yfYxifGmxbjDv[kBJW1B{Nx?= M4DRWVE5Ozl5M{S1
RPMI-LR5 M2HuU2tqdmG|ZTDhd5NigQ>? MV;+PFAxKG6P NXfpOGZyTE2VTx?= MXjpcohq[mm2czDwbI9{eGixconsZZRqd25ib3[gTHNROjd? NHvDfYsyQDN7N{O0OS=>
INA-6 M3PZNGtqdmG|ZTDhd5NigQ>? NVLaT5ZKhjhyMDDuUS=> MkLuSG1UVw>? NGWxRoRqdmirYnn0d{BxcG:|cHjvdplt[XSrb36gc4YhUFOSMke= M4nsVFE5Ozl5M{S1
RPMI-8226 NVHKSmlXS3m2b4jpZ4l1gSCjc4PhfS=> MnzlglExODBibl2= MnrHSG1UVw>? NWHGTok6dm9ic3nncolncWOjboSgZ5l1d3SxeHnjbZR6 MVyxPFM6PzN2NR?=
U266 Mn7YR5l1d3irY3n0fUBie3OjeR?= NUnNZZI3hjFyMECgcm0> M2\kPWROW09? MX7uc{B{cWewaX\pZ4FvfCCleYTveI95cWOrdIm= MXmxPFM6PzN2NR?=
MM.1S NH\hNpNEgXSxeHnjbZR6KGG|c3H5 NEPqVWR,OTByMDDuUS=> M2CyOWROW09? NHPIWI9vdyC|aXfubYZq[2GwdDDjfZRwfG:6aXPpeJk> M1qxdFE5Ozl5M{S1
RPMI-Dox40 M4[3SWN6fG:6aXPpeJkh[XO|YYm= MonUglExODBibl2= NXXKeY9TTE2VTx?= MXvuc{B{cWewaX\pZ4FvfCCleYTveI95cWOrdIm= NVPy[YhvOTh|OUezOFU>
RPMI-LR5 MUTDfZRwgGmlaYT5JIF{e2G7 M1mzTZ4yODByIH7N MlrHSG1UVw>? MkPNco8he2mpbnnmbYNidnRiY4n0c5RwgGmlaYT5 NEKyOoYyQDN7N{O0OS=>
INA-6 NV:5dFZRS3m2b4jpZ4l1gSCjc4PhfS=> MlvCglExODBibl2= M2niRWROW09? NHPt[oxvdyC|aXfubYZq[2GwdDDjfZRwfG:6aXPpeJk> M2KxS|E5Ozl5M{S1
CD14+ MX3GeY5kfGmxbjDhd5NigQ>? NWLlT4ZYhjhyMDDuUS=> MWTEUXNQ NELoW4NqdmirYnn0d{Bwe3Snb3PsZZN1d2enbnXzbZMh\nKxbTDDSFE1KHCxc3n0bZZmKGOnbHzz NVLQd|Y6OTh|OUezOFU>
U-87-MG MmPVSpVv[3Srb36gZZN{[Xl? NEjYcVEyKM7:TR?= NX;IZ2JpTE2VTx?= NF;VV2Jz\WS3Y3XzJJR2dW:{LXTybZZmdiClb4LkJIZwem2jdHnvci=> NV7vOWlEOjN|M{W1NFY>
MDA-MB-231 M3fofmZ2dmO2aX;uJIF{e2G7 NWGwfYN[OSEQvF2= NFX1OHBFVVOR MYHy[YR2[2W|IIT1cY9zNWS{aY\lckBkd3KmIH\vdo1ifGmxbh?= M3TtbFI{OzN3NUC2
A-2780 MnzXSpVv[3Srb36gZZN{[Xl? MmrSNUDPxE1? Mln1SG1UVw>? M{X0dpJm\HWlZYOgeJVud3JvZILpeoVvKGOxcnSg[o9zdWG2aX;u NFHGTI4zOzN|NUWwOi=>
SK-OV-3 MlzUSpVv[3Srb36gZZN{[Xl? MlT4NUDPxE1? NEXCOZhFVVOR M4TqZ5Jm\HWlZYOgeJVud3JvZILpeoVvKGOxcnSg[o9zdWG2aX;u MoDnNlM{OzV3ME[=
LXFA-629 MUnGeY5kfGmxbjDhd5NigQ>? MXSxJO69VQ>? NFXyNlNFVVOR Ml\NdoVlfWOnczD0eY1wei2mcnn2[Y4h[2:{ZDDmc5Ju[XSrb36= MXKyN|M{PTVyNh?=
NCI-H1650 M{HMRWZ2dmO2aX;uJIF{e2G7 MmPvNUDPxE1? MYnEUXNQ NYqxUWtremWmdXPld{B1fW2xcj3kdol3\W5iY3;y[EBnd3KvYYTpc44> MmrLNlM{OzV3ME[=
PC-3 M4WwemZ2dmO2aX;uJIF{e2G7 MUWxJO69VQ>? M3vQ[mROW09? Mlm0doVlfWOnczD0eY1wei2mcnn2[Y4h[2:{ZDDmc5Ju[XSrb36= NHHrenMzOzN|NUWwOi=>
RAW264.7 M2T0T2Z2dmO2aX;uJIF{e2G7 NFPTSZZ,OjBizszN M{CxSGROW09? NFfaR2dqdmirYnn0d{BCdmm|b335Z4lvNXO2aX31cIF1\WRiTVuyJJBpd3OyaH;yfYxifGmxbjD3bZRpKEmFNUCgc4YhOzVwMzDuUS=> M4\FWVI1OzV4OEG0
mouse peritoneal macrophages NE\aSG9HfW6ldHnvckBie3OjeR?= NYDLNJFrhjJyIN88US=> M4PUd2ROW09? M1HsUGxRWy:LRl6t{tPjiJO|dHnteYxifGWmIGTOSk3PuSCycn;keYN1cW:wIIfpeIghUUN3MDDv[kA3NjNibl2= NH7pRXAzPDN3NkixOC=>
A549 NFG3e2lHfW6ldHnvckBie3OjeR?= MofJglIxKM7:TR?= MnvoSG1UVw>? NUj1bmxlcW6qaXLpeJMhVFCVLXnu[JVk\WRiQ2jDUFgheHKxZIXjeIlwdiC5aYToJGlEPTBib3[gNVQ1Njlibl2= M37VPFI1OzV4OEG0
MDA-231 M4TLVWZ2dmO2aX;uJIF{e2G7 MVX+NVAh|ryP NHX4e|R{fXCycnXzd4V{KESNSz2xJIV5eHKnc4Ppc44> M4O2V|I3PDB5OESz
MCF-7 MYPGeY5kfGmxbjDhd5NigQ>? NFKwOVR,OTBizszN MmS3d5VxeHKnc4Pld{BFU0tvMTDlfJBz\XO|aX;u M4nNOlI3PDB5OESz
MDA-435 NWmzWlV3TnWwY4Tpc44h[XO|YYm= MWj+NVAh|ryP MVzzeZBxemW|c3XzJGRMUy1zIHX4dJJme3Orb36= NFzpXFczPjRyN{i0Ny=>
PC3 NE\MfYNHfW6ldHnvckBie3OjeR?= Mof3glExKM7:TR?= MULEUXNQ NU\WN2dWe3WycILld5NmeyCGS1utNUBmgHC{ZYPzbY9v MYCyOlkyOzZyOB?=

... 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)

技術サポート&よくある質問(FAQ)

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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