Dasatinib 化学構造
分子量: 488.01

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Quality Control & MSDS

製品説明

  • Compare Src Inhibitors
    Src製品生物活性の比較
  • 研究分野
  • Combination Therapy
    併用療法

製品の説明

生物活性

製品説明 Dasatinib は、野生型ablとSrcのためのSrc/abl阻害剤で、IC50 がそれぞれ 0.6 nM と 0.8 nMです。
ターゲット Abl Src c-Kit (WT)/c-Kit (D816V)
IC50

0.6 nM

0.8 nM [1]

79 nM/37 nM [2]
In vitro試験 Dasatinib is more effective than imatinib in inhibiting the proliferation of Ba/F3 cells expressing wild-type Bcr-Abl and Bcr-Abl mutants, with the exception of T315I. Dasatinib has a two-log (∼325-fold) increased potency relative to imatinib. Dasatinib potently inhibits wild-type Abl kinase and all mutants except T315I over a narrow range. Dasatinib directly targets wild-type and mutant Abl kinase domains and inhibits autophosphorylation and substrate phosphorylation in a concentration-dependent manner. Dasatinib displays 325-fold greater potency compared with imatinib against cells expressing wild-type Bcr-Abl. [1] The percent of colonies of TgE bone marrow cells are decreased from 100% in untreated wells to 4.12% in Dasatinib treated wells. In the presence of Dasatinib, the difference in the percentage of colonies formed by WT and TgE bone marrow cells is statistically significant. Expression of LMP2A is able to promote B lymphocyte survival and proliferation, which can be inhibited by targeting Lyn and/or c-Abl kinases through Dasatinib. [3] Dasatinib treatment inhibits Src signaling, decreases growth, and induces cell cycle arrest and apoptosis in a subset of thyroid cancer cells. Treatment with increasing doses of Dasatinib (0.019 μM to 1.25 μM) for 3 days inhibits the growth of the C643, TPC1, BCPAP, and SW1736 cell lines by about 50% at low nanomolar concentrations, while higher concentrations are required to inhibit the growth of the K1 cell line. Treatment with 10 nM or 50 nM Dasatinib results in a 9-22% increase of cells in the G1 population among BCPAP and SW1736 and K1 cells, and a corresponding 7-18% decrease in the percentage of cells in the S phase. [4]
Cell Data
Cell LinesAssay TypeConcentrationIncubation TimeFormulationActivity Description
M07ep210 MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWe3NkBp MnrsSG1UVw>? NInPU4ZKSzVyPUCuNFAxODdizszN
K562 NELmcVBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4TpOFczKGh? NGnk[5ZFVVOR M2nsUmlEPTB;MD6wNFEh|ryP
M07e NYHBcXZmT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWDJZXdqPzJiaB?= NYLreYQ6TE2VTx?= NXfSXI5mUUN3ME2wMlAxOTJizszN
ALL3 MlvMR5l1d3SxeHnjJGF{e2G7 MWWwMlHPxE1? NHfMTYk4OiCq NXXTfWhKTE2VTx?= M4nMNmlEPTB;MD6wNFA1KM7:TR?=
CML NWjYZpc5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4DXcFIxKG2rbh?= MoHLSG1UVw>? NU\odVhFUUN3ME2wMlAxOSEQvF2=
BA/F3 MkjJS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3;uS|czKGh? NFjFWZNFVVOR NEXTdHRKSzVyPU[uOVg6KM7:TR?=
BA/F3 NHjXOVlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmnOO|IhcA>? NFvkepdFVVOR MojETY5lfWOnczDhcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IH3veZNmKEKDL1[zJINmdGy|IHX4dJJme3OrbnegRoNzNUGkbDDNN|UyXCCvdYThcpQhf2m2aDDJR|UxKG:oIECuNFAxQDQQvF2=
BA/F3 M2P5emdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NI\XOYY4OiCq MVrEUXNQ MUPJcoR2[2W|IHHueIlxem:uaX\ldoF1cX[nIHHjeIl3cXS7IHHnZYlve3RibX;1d4UhSkFxRkOgZ4VtdHNiZYjwdoV{e2mwZzD3bYxlKHS7cHWgRoNzNUGkbDD3bZRpKEmFNUCgc4YhOC5yMES1{txO
BA/F3 M1nKUWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MojHO|IhcA>? Mom5SG1UVw>? NU\yNINDUW6mdXPld{BidnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JI1wfXOnIFLBM2Y{KGOnbHzzJIV5eHKnc4PpcochSmO{LVHicEBVOzF3STDteZRidnRid3n0bEBKSzVyIH;mJFEvPzF2zszN
BA/F3 Mnq3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXi3NkBp MmXZSG1UVw>? NWPwR3VUUW6mdXPld{BkgXSxdH;4bYNqfHliYXfhbY5{fCCvb4Xz[UBDSS:IMzDj[YxteyCneIDy[ZN{cW6pIFLDVk1CSkxiRkS4OnMhdXW2YX70JIF{e2W|c3XkJIF{KGe{b4f0bEBKdmirYnn0bY9vKHerdHigTWM2OCCxZjCwMlAxODoQvF2=
BA/F3 MoPUS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGO2eJo4OiCq Ml\xSG1UVw>? M3fz[Glv\HWlZYOgZ5l1d3SxeHnjbZR6KGGpYXnud5QhdW:3c3WgRmEwTjNiY3XscJMh\XiycnXzd4lv\yCEQ2KtRWJNKEV{NUXLJI12fGGwdDDhd5Nme3OnZDDhd{Boem:5dHigTY5pcWKrdHnvckB4cXSqIFnDOVAhd2ZiMD6wNFMz|ryP
BA/F3 MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUC3NkBp Mk\KSG1UVw>? NH73cWlKdmS3Y3XzJIN6fG:2b4jpZ4l1gSCjZ3HpcpN1KG2xdYPlJGJCN0Z|IHPlcIx{KGW6cILld5NqdmdiQlPSMWFDVCCJMkWwSUBufXSjboSgZZN{\XO|ZXSgZZMh\3Kxd4ToJGlvcGmkaYTpc44hf2m2aDDJR|UxKG:oIECuNFA2Oc7:TR?=
BA/F3 NWrQUXM{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVz4d3huPzJiaB?= NYqybGVWTE2VTx?= MkDvTY5lfWOnczDjfZRwfG:6aXPpeJkh[WejaX7zeEBud3W|ZTDCRU9HOyClZXzsd{BmgHC{ZYPzbY5oKEKFUj3BRmwhWTJ3MligcZV1[W62IHHzd4V{e2WmIHHzJIdzd3e2aDDJcohq[mm2aX;uJJdqfGhiSVO1NEBw\iByLkCwPO69VQ>?
BA/F3 NFj5So9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHO4fHA4OiCq MoC4SG1UVw>? MnP0TY5lfWOnczDjfZRwfG:6aXPpeJkh[WejaX7zeEBud3W|ZTDCRU9HOyClZXzsd{BmgHC{ZYPzbY5oKEKFUj3BRmwhTTN3OW[gcZV1[W62IHHzd4V{e2WmIHHzJIdzd3e2aDDJcohq[mm2aX;uJJdqfGhiSVO1NEBw\iByLkCwNVPPxE1?
BA/F3 MkjwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkDZO|IhcA>? NGfXcXJFVVOR M17LSmlv\HWlZYOgZ5l1d3SxeHnjbZR6KGGpYXnud5QhdW:3c3WgRmEwTjNiY3XscJMh\XiycnXzd4lv\yC5aXzkJJR6eGViQlPSMWFDVCCjc4Pld5Nm\CCjczDndo94fGhiSX7obYJqfGmxbjD3bZRpKEmFNUCgc4YhOC5yMEG5{txO
BA/F3 NVfYcIhYT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXy3NkBp MWTEUXNQ M3jj[2lv\HWlZYOgZ5l1d3SxeHnjbZR6KGGpYXnud5QhdW:3c3WgRmEwTjNiY3XscJMh\XiycnXzd4lv\yCEQ2KtRWJNKFl{NUPIJI12fGGwdDDhd5Nme3OnZDDhd{Boem:5dHigTY5pcWKrdHnvckB4cXSqIFnDOVAhd2ZiMD6wNFI{|ryP
BA/F3 MnnoS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnzMO|IhcA>? M1ewdGROW09? M1PuZWlv\HWlZYOgZ5l1d3SxeHnjbZR6KGGpYXnud5QhdW:3c3WgRmEwTjNiY3XscJMh\XiycnXzd4lv\yCEQ2KtRWJNKFR|MUXJJI12fGGwdDDhd5Nme3OnZDDhd{Boem:5dHigTY5pcWKrdHnvckB4cXSqIFnDOVAhd2ZiMz62{txO
BA/F3 MnSzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M375XFczKGh? NWP5bnlQTE2VTx?= MmjETY5lfWOnczDjfZRwfG:6aXPpeJkh[WejaX7zeEBud3W|ZTDCRU9HOyClZXzsd{Bie3Onc4Pl[EBieyCpcn;3eIghUW6qaXLpeIlwdiC5aYToJGlEPTBib3[gNk42|ryP
T cell NGDpb4RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmTtO|IhcA>? MVLEUXNQ MWnJcohq[mm2czDhcpRqKEOGMz2gZY5lKGGwdHmgR2QzQC2rbnT1Z4VlKFRiY3XscEBxem:uaX\ldoF1cW:wIIfpeIghUUN3MDDv[kAxNjByM988US=>
WiDr M3rtTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXi3NkBp NYH4RWhZTE2VTx?= NWTvcmhbUUN3ME2wMlA2OiEQvF2=
PC3 MlX5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NILUXVU4OiCq MYrEUXNQ NWD3PFhjUUN3ME2wMlAxQTRizszN
MDA-MB-231 NXzPNGdpT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NF\xZ2Y4OiCq MkLlSG1UVw>? MYPJR|UxRTBwMEGyJO69VQ>?
Hs578T M3i2T2N6fG:2b4jpZ{BCe3OjeR?= MkftO|IhcA>? MVTEUXNQ MnfzS2k2OD1yLkCzJO69VQ>?
HMEC MkHBR5l1d3SxeHnjJGF{e2G7 NG\G[mo4OiCq NHjoOldFVVOR NVPaXYtUT0l3ME2xMlgh|ryP
DU145 MYXDfZRwfG:6aXOgRZN{[Xl? Mn34O|IhcA>? MkS0SG1UVw>? NFSz[pRIUTVyPUCuNVYh|ryP
U251 MXXDfZRwfG:6aXOgRZN{[Xl? NVrLZYEyPzJiaB?= M3vJSmROW09? MlLiS2k2OD1{LkixJO69VQ>?
NCI60 NXPz[odbS3m2b4TvfIlkKEG|c3H5 MWO3NkBp MmfnSG1UVw>? Mnu4S2k2OD13Lkeg{txO
MALME-3M NXjuS3lFS3m2b4TvfIlkKEG|c3H5 MYq3NkBp MXnEUXNQ NWTycXo{T0l3ME22MlYyKM7:TR?=
KM12 MXnDfZRwfG:6aXOgRZN{[Xl? NUD5d2c3PzJiaB?= MmDkSG1UVw>? NFHxcmtIUTVyPUeuOFQh|ryP
SW620 M3vaS2N6fG:2b4jpZ{BCe3OjeR?= M4jSW|czKGh? NHKwN|ZFVVOR M2PXbmdKPTB;OD60N{DPxE1?
RXF 393NL MkDmR5l1d3SxeHnjJGF{e2G7 NYfIdHFXPCCmYYnz Mni4SG1UVw>? M{\RNWlEPTB;MD6wNlE4KM7:TR?=
LXFA 983L MmjQR5l1d3SxeHnjJGF{e2G7 M{XJcVQh\GG7cx?= M2q0eWROW09? NXL2[4FWUUN3ME2wMlA2PjVizszN
PRXF DU145 MVXDfZRwfG:6aXOgRZN{[Xl? MYW0JIRigXN? Mn:5SG1UVw>? MY\JR|UxRTBwME[yN{DPxE1?
PAXF 1657L Ml20R5l1d3SxeHnjJGF{e2G7 NUjidZh1PCCmYYnz NUDSS5p2TE2VTx?= MknBTWM2OD1yLkGyNUDPxE1?
CXF 1103L MUDDfZRwfG:6aXOgRZN{[Xl? MVW0JIRigXN? M{TtXWROW09? NFP3cIZKSzVyPUSuN|Yh|ryP
GXF251L MonFR5l1d3SxeHnjJGF{e2G7 NELTSm01KGSjeYO= M37u[WROW09? NXToRmRQUUN3ME2yMlI2KM7:TR?=
NCI-H23 NEXqV5ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmjqO|IhcA>? MWfEUXNQ NFTSNXVKSzVyPUKuNlch|ryP
HCT116 M1fRPGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1;nNlczKGh? M2riSGROW09? NWTXZ3JwUUN3ME2yMlMh|ryP
MCF7 M4LySWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUXV[pNmPzJiaB?= NFzDfpBFVVOR NEHOdI1KSzVyPUKuOVch|ryP
NCI-H460 M3j4O2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4H6dVczKGh? NH\TeHBFVVOR MX\JR|UxRThwOUmg{txO
DLD1 MnfTS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUO3NkBp MUDEUXNQ NXXi[VdDUUN3ME20MlYh|ryP
NCI-H661 MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkmyO|IhcA>? M3jjV2ROW09? NV3wUG5sUUN3ME23Mlgh|ryP
A549 MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Ml3vO|IhcA>? NFG1W45FVVOR NGrTSpRKSzVyPUiuNkDPxE1?
U937 NVnNVnJRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVi3NkBp NX\Y[m85TE2VTx?= M1LHV2lEPTB;MUKuNkDPxE1?
HEK293 M2G2UmZ2dmO2aX;uJGF{e2G7 NHe3eWoyOMLizszN MWrEUXNQ NFv5ZZRKdmS3Y3XzJIJqdmSrbnegZYZncW6rdImgeI8hcHWvYX6g[pVtdC2uZX7neIghUGm|LYTh[4dm\CCPeYSxJItqdmG|ZTDlfJBz\XO|ZXSgbY4hUEWNMkmzJINmdGy|IIfpeIghUUN3MDDv[kAxNjB4M988US=>
HUVEC NXT5PHhxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVKwMlE2yqEQvF2= MmL1O|IhcA>? NX[wb5k2TE2VTx?= NWS0[ItsUW6mdXPld{BidnSrYX7nbY9o\W6rYzDhZ5Rqfmm2eTDpckBJXV[HQzDjc{1kfWy2dYLl[EB4cXSqII\hd4N2dGG{IIPtc491cCCvdYPjcIUh[2WubIOgZZN{\XO|ZXSgZZMhUW6qaXLpeIlwdiCxZjDj[YxtKGe{b4f0bEBifCByLkG1JJVO
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Plasmodium falciparum MYrGeY5kfGmxbjDBd5NigQ>? M2rsclExyqEQvF2= MUWxOUBucW5? MWHEUXNQ NGOzOnhKdmirYnn0d{BRdGG|bX;kbZVuKG[jbHPpdIFzfW1icILvcIln\XKjdHnvckBjgSCrbnjpZol1cW6pIITo[UBHfW6ldHnvckBw\iCSZlPEVGsyKHC{b4TlbY4hf2m2aDDJR|UxKG:oIEGuNVfPxE1?
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DU145 M3W4T2Z2dmO2aX;uJGF{e2G7 MmnWNE4yKM7:TR?= M2HVO|UhcA>? MnXOSG1UVw>? NF3tWo1KdmirYnn0d{BpfW2jbjDEWVE1PSClZXzsJIFlcGW|aX;uJIF1KDFyMDDuUS=>
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BL-70 M1LWXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGXYd3pKSzVyPUCuNFAxODByOEKyJO69VQ>?
EM-2 M4DMbWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MV\JR|UxRTBwMECwNFAyODhizszN
LAMA-84 MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlPtTWM2OD1yLkCwNFAxOzJzIN88US=>
MEG-01 M4LTR2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1XQNGlEPTB;MD6wNFAxODl6IN88US=>
EoL-1-cell Mm\xS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnXsTWM2OD1yLkCwNFAyOzFizszN
CTV-1 MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXfYT4F7UUN3ME2wMlAxODB2MESg{txO
TE-15 M1O3eWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEjUVVdKSzVyPUCuNFA2QDlizszN
NOS-1 MoPCS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MX7JR|UxRTBwMEC2NVMh|ryP
D-336MG NGXrNWlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEH0eGVKSzVyPUCuNFA3OyEQvF2=
LB1047-RCC NEPZNlZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnTzTWM2OD1yLkCwPVg6KM7:TR?=
LB996-RCC M2fBN2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MknjTWM2OD1yLkCwPVkyKM7:TR?=
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OVCAR-4 NHnKcldIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2PadWlEPTB;MD6zO|Q{OyEQvF2=
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OCUB-M M4XEN2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NH\zR5RKSzVyPUGuNFQ1OTJizszN
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NCI-H1838 NGDaWWtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUTJR|UxRTFwM{C3N|Mh|ryP
NKM-1 MnnrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{j2TGlEPTB;MT6zNFg2QSEQvF2=
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HCE-T M1vzXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NF7hSWtKSzVyPUGuOVY4OTRizszN
SBC-1 MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoHOTWM2OD1zLkW3PVg1KM7:TR?=
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JVM-2 NFzq[ZlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVPpSYNLUUN3ME2yMlM3Ojh2IN88US=>
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MV-4-11 MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{HmdGlEPTB;ND6zOlQ2PCEQvF2=
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DJM-1 MmDHS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVHJR|UxRTZwNEi1OVgh|ryP
RPMI-6666 MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4rMUGlEPTB;Nz6yO|A3PyEQvF2=
KARPAS-45 NVzFb|hrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoXNTWM2OD15LkWxOlcyKM7:TR?=
LP-1 MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUfJR|UxRTdwNUS3PFIh|ryP
RS4-11 MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoKwTWM2OD15Lk[1O|g4KM7:TR?=
DU-4475 M3e2bmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MW\JR|UxRThwMkG2OVIh|ryP
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NCI-SNU-16 NHm0T4tIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NX;kTmRrUUN3ME24MlU3OTJ6IN88US=>
SJSA-1 M1;ab2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGm4XoxKSzVyPUiuO|I5ODVizszN
MMAC-SF NHrQZ|dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NH;odXJKSzVyPUiuO|k{ODdizszN
SK-NEP-1 MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmrUTWM2OD16Lki5NVU2KM7:TR?=
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SKM-1 NV7uenVzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mn;zTWM2OD17LkCxO|M1KM7:TR?=
LB2241-RCC M3zESGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NF;UXGZKSzVyPUmuNFIxOTJizszN
SIG-M5 Mmm0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlfPTWM2OD17LkCyOFk{KM7:TR?=
EVSA-T M2LKXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYHJR|UxRTlwMke3PVMh|ryP
GT3TKB NET6dZZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnfiTWM2OD17LkO1OVQ3KM7:TR?=
NB6 NGTmdpdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFPWWZZKSzVyPUmuPVIzPTlizszN
EHEB NF:yPXRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Ml3QTWM2OD1zMD6wOlU3KM7:TR?=
HEL MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1HzdWlEPTB;MUCuOFc4PiEQvF2=
ALL-PO MnzFS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWi1R2UzUUN3ME2xNE44QTN6IN88US=>
TGW NFrifY1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXzJR|UxRTFzLkK4Nlgh|ryP
BC-3 NX3TPHprT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXXPeVFsUUN3ME2xNk4yOTN6IN88US=>
IA-LM M4fIUmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MojITWM2OD1zMj60OFQ2KM7:TR?=
UACC-257 NHHR[5VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFr2W3dKSzVyPUGyMlkyQThizszN
KP-N-YS NWjJR5dDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXX2bW4{UUN3ME2xNk46Ojh|IN88US=>
Raji NITaeGNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGT6S3NKSzVyPUGzMlc1QTdizszN
SF539 NVLB[5dxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NX;vT444UUN3ME2xN{45PTV5IN88US=>
DMS-153 M{nYeGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2C4UWlEPTB;MUSuNFAzQCEQvF2=
L-540 MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1KycWlEPTB;MUWuNFY4OiEQvF2=
MN-60 M1XhOGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGnOWoZKSzVyPUG1MlE6PzlizszN
RPMI-8866 M3nwOmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVrJR|UxRTF5LkS0OVQh|ryP
NCI-H510A NGjP[ldIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2jmemlEPTB;MUmuN|k4OyEQvF2=
NB13 NUPOWZprT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{DFbGlEPTB;MUmuOFg4PyEQvF2=
HAL-01 NWn5VGd{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYWyWnZUUUN3ME2xPU44PTR|IN88US=>
NCI-H720 M2XMOWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHTIN|BKSzVyPUKwMlI4OzNizszN
REH NXT4cYFbT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHzyT5ZKSzVyPUKwMlY{PTdizszN
KNS-81-FD M1jwUmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXn3dIlHUUN3ME2yN{4yPDZizszN
HC-1 NW\He5ZWT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NES5[ZBKSzVyPUK0MlU2PTFizszN
NCI-H2141 MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnPQTWM2OD1{ND63O|U1KM7:TR?=
MOLT-4 NFPSfmRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NU\STFhDUUN3ME2yOk43PzV|IN88US=>
OMC-1 M{i0e2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWHJR|UxRTJ5LkG0NlIh|ryP
LC-1F NIfqPVdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEXHTZhKSzVyPUK3MlMzPDVizszN
NCI-H1304 MoDES5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmLFTWM2OD1{OD6xOlI5KM7:TR?=
BC-1 NVG5[GoyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoHwTWM2OD1{OD62OVEh|ryP
NCI-H64 M{H4bWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3XpcmlEPTB;MkmuOlI2OyEQvF2=
MOLT-16 NEnwbXBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnWyTWM2OD1{OT62NlkzKM7:TR?=
U-87-MG MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGfNNYtKSzVyPUOwMlc3PiEQvF2=
GAK NHjKZWpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVnJR|UxRTNzLkK2PFYh|ryP
ES8 NYjFV4xZT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mm\rTWM2OD1|Mj6xNlUzKM7:TR?=
HCC1599 NYOxeXRxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVK5[oU3UUN3ME2zNk4{OzJ3IN88US=>
EB-3 M1HlPWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEn2b5BKSzVyPUO0MlMyOTdizszN
HCC1187 NV3jR3BIT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXjJR|UxRTN3LkiwOVIh|ryP
SK-PN-DW NEPFbHFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYPqRYZbUUN3ME2zOk4yQTR|IN88US=>
JVM-3 M{XQ[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NU\veZZvUUN3ME2zO{4zOzN6IN88US=>
HCC2157 NWnhdVR4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mn7pTWM2OD1|Nz65PVQ3KM7:TR?=
A4-Fuk MkjqS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYPxPG9uUUN3ME2zPE4yODB7IN88US=>
COR-L279 MXTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGDzfIRKSzVyPUSwMlI5PTFizszN
DEL M2\xU2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{\nXWlEPTB;NEGuPVA5PiEQvF2=
NCI-H1395 NX\BR2xkT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{HTT2lEPTB;NEKuNFE3OyEQvF2=
MHH-NB-11 NWO1VYhOT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXPJR|UxRTR|LkC4NVgh|ryP
NCI-H2107 M2Wxemdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoG4TWM2OD12Mz60PFQ3KM7:TR?=
NEC8 MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUSybGpjUUN3ME20OE4{OzZizszN
COLO-684 NWfJ[29yT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXzJR|UxRTR4LkKyOVgh|ryP
LS-411N NGP1VY9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NF32Xm5KSzVyPUS4MlQ4PDhizszN

... Click to View More Cell Line Experimental Data

In vivo試験 Dasatinib reverses splenomegaly in LMP2A/MYC double transgenic mice. Dasatinib specifically prevents colony formation by LMP2A expressing bone marrow B cells and decreased spleen size in the TgE mice. Spleen mass is significantly decreased among Dasatinib treated Tg6/λ-MYC mice when compared to the control group. Dasatinib inhibits lymphadenopathy in LMP2A/MYC double transgenic mice. Dasatinib reverses splenomegaly in Rag1KO mice engrafted with tumor cells from LMP2A/MYC double transgenic mice. Dasatinib therapy inhibits Lyn phosphorylation in B lymphocyte tumors expressing LMP2A. [3]
臨床試験 Dasatinib has entered in a phase II clinical trial in the treatment of hemangiopericytoma and gastrointestinal stromal tumor.
特集

プロトコル (参考用のみ)

キナーゼアッセイ:

[1]

Kinase autophosphorylation assays Kinase assays using wild-type and mutant glutathione S-transferase (GST)-Abl fusion proteins (c-Abl amino acids 220-498) are done. GST-Abl fusion proteins are released from glutathione-Sepharose beads before use; the concentration of ATP is 5 μM. Immediately before use in kinase autophosphorylation and in vitro peptide substrate phosphorylation assays, GST-Abl kinase domain fusion proteins are treated with LAR tyrosine phosphatase. After 1-hour incubation at 30 °C, LAR phosphatase is inactivated by addition of sodium vanadate (1 mM). Immunoblot analysis comparing untreated GST-Abl kinase to dephosphorylated GST-Abl kinase is routinely done using phosphotyrosine-specific antibody 4G10 to confirm complete (>95%) dephosphorylation of tyrosine residues and c-Abl antibody CST 2862 to confirm equal loading of GST-Abl kinase. The Dasatinib concentration range is extended to 1,000 nM for mutant T315I. These same inhibitor concentrations are used for the in vitro peptide substrate phosphorylation assays. The three inhibitors are tested over these same concentration ranges against GST-Src kinase and GST-Lyn kinase.

細胞アッセイ:

[1]

細胞株 Ba/F3 cell lines
濃度 ~32 nM
反応時間 72 hours
実験の流れ

Ba/F3 cell lines are seeded in triplicate and incubated with escalating concentrations of Dasatinib for 72 hours. Proliferation is measured using a methanethiosulfonate-based viability assay. IC50 and IC90 values are reported as the mean of three independent experiments done in quadruplicate. The inhibitor concentration ranges are 0 nM to 32 nM (Dasatinib). The Dasatinib concentration range is extended to 200 nM for mutant T315I.

動物実験:

[3]

動物モデル EμLMP2A (TgE and Tg6 strains), MYC (λ-MYC), and LMP2A/λ-MYC double transgenic mice (Tg6/λ-MYC)
製剤 DMSO
投薬量 30 mg/kg
投与方法 Administered via i.p.

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 Dasatinib SDF
分子量 488.01
化学式

C22H26ClN7O2S

CAS No. 302962-49-8
保管 2年-20℃
6月-80℃in solvent
別名 BMS-354825
溶解度 (25°C) * In vitro DMSO 98 mg/mL (200.81 mM)
<1 mg/mL (<1 mM)
エタノール <1 mg/mL (<1 mM)
In vivo 1% DMSO/30% polyethylene glycol/1% Tween 80 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 N-(2-chloro-6-methylphenyl)-2-(6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-ylamino)thiazole-5-carboxamide

カスタマーフィードバック (10)


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Rating
Source Cell Res, 2011, 21, 1080-1087. Dasatinib purchased from Selleck
Method Microangiography
Cell Lines embryos
Concentrations 30 μM
Incubation Time
Results MEK1/2 may cooperate with VEGFR to regulate blood vessel lumen diameter. We examined this hypothesis by combining VEGFR inhibitor Sunitinib and MEK1/2 inhibitor U0126. Indeed, U0126 (10 µM) combined with Sunitinib (20 µM) resulted in a reduction of vessel lumen size (Figure F), whereas individually they did not. Combined treatment of another MAP kinase signaling pathway inhibitor Dasatinib (20 µM) with Sunitinib (20 µM) produced a similar phenotype as PP1, whereas each individual inhibitor did not result in any vessel shrinkage even at much higher concentrations ( Figure C).Since there are three major VEGF receptors, it is desirable to determine which receptor is involved in combinatory action with MEK1/2. To address this issue, additional highly selective VEGFR inhibitors PTK787 and ZM323881 were tested. Both of these inhibitors (PTK787 or ZM323881), when individually combined with Dasatinib or U0126, induced a reduction of vessel lumen size (Figure D, E, G, and H).

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Rating
Source Clin Cancer Res, 2011, 17, 762-770. Dasatinib purchased from Selleck
Method Assessment of cell viability and apoptosis
Cell Lines B-CLL patient leukemic cells
Concentrations 2-10 μM
Incubation Time 48 h
Results The Dasatinib+Nutlin-3 combination promotes synergistic cytotoxicity in primary CLL cells as well as in p53 wild-type and p53 deleted/ mutated leukemic cell lines.

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Rating
Source Clin Cancer Res, 2011, 17, 762-770. Dasatinib purchased from Selleck
Method Western blot
Cell Lines Leukemic cell lines
Concentrations 10 μM
Incubation Time 24 h
Results Dasatinib marginally affected both the basal levels of p53 and the accumulation of p53 induced by Nutlin-3 in the p53 wild -type cells (Fig. A).Interestingly, however, levels of both MDM2 and p21 proteins, 2 of the best characterized transcriptional targets of p53, weres significantly (P < 0.05) decreased in cells treated with Dasatinib+ Nutlin-3 with respect to cells treated with Nutlin-3 alone (Fig. B).

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Rating
Source Clin Cancer Res, 2011, 17, 762-770. Dasatinib purchased from Selleck
Method Phospho-kinase array analysis
Cell Lines EHEB cell lines/BJAB cell lines
Concentrations 10 μM
Incubation Time 16 h
Results Although Nutlin-3 had no effects on these pathways, Dasatinib alone as well as Dasatinib+Nutlin-3 markedly inhibited the basal phosphorylation of ERK1/2, p38/MAPK, and Akt . Of interest, the combination of Dasatinib+Nutlin-3 selectively enhanced (P < 0.05) the inhibition of Akt phosphorylation with respect to Dasatinib alone, as validated by Western blot analysis.

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Rating
Source Biochem Pharmacol , 2011, 82, 1457-1466. Dasatinib purchased from Selleck
Method MTT assay
Cell Lines MOLM-13 cells, HL-60 cells
Concentrations 1-15 μM
Incubation Time 24-72 h
Results Dasatinib and other TKI decreased the viability of the two myeloid cell lines in a dose- and time-dependent manner. Nevertheless, the anti-leukemic efficacy of Dasatinib and other TKI varied considerably in both cell lines.

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Rating
Source Biochem Pharmacol , 2011, 82, 1457-1466. Dasatinib purchased from Selleck
Method Evaluation of differentiation
Cell Lines MOLM-13 cells, HL-60 cells
Concentrations 5 μM
Incubation Time
Results In a first series of experiments, we assessed four signs of morphological differentiation, May-Gruenwald-Giemsa staining of MOLM-13 cells demonstrated that dasatinib induced a dose-dependent decrease in cytoplasmic basophilia and in the nucleo-cytoplasmic ratio. Dasatinib also led to the appearance of dented nuclei and cytoplasmic granulation( Fig.A and B).In HL-60 cells,dasatinib(5 μM) once more exhibited the highest differentiation-inducing capacity. Thus dasatinib diminished basophilia of the cytoplasm concomitantly with the nucleo-cytoplasmic ratio, and induced the appearance of nuclear lobulation and cytoplasmic granules(Fig. G). Next, we determined the degree of CD11b expression, a marker indicating myeloid differentiation, in TKI-treated MOLM-13 dasatinib exhibited the most pronounced capacity to increase CD11b surface expression( Fig. C and D).To corroborate the TKI-driven differentiation, we quantified the enzymatic activity of alkaline phosphatase by means of the NBT-reduction assay after an incubation period of 6 days in MOLM-13 cells.,Once again, the NBT-reductive activity was highest in cells treated with dasatinib, which was as active as the positive control, ATRA( Fig. E and F)

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Rating
Source Invest New Drugs , 2010, 30, 417-422. Dasatinib purchased from Selleck
Method Assessment of cell viability
Cell Lines leukemic cells
Concentrations 10 μM
Incubation Time 24/48 h
Results Dasatinib dose-dependently reduced cell viability in all leukemic cell lines, with variable efficacy irrespect ively of the p53 status. In particular, when used at 10 μM, Dasatinib induced a progressive decrease of the total number of viable cells ranging from approximately 30% (JVM-2 and MEC-2) to 50% (EHEB and BJAB) after 48 h of treat ment (Fig.a). In order to investigate whet her the decreased leukemic cell viability was mainly due to either cytotoxic or cytostatic activity, we have analyzed the effects of Dasatinib on apoptosis,As shown in Fig. b, exposure to Dasatinib induced a significant (p < 0.05) increase of apoptosis in all leukemic cell lines, as evaluated by Annexin-V/PI staining at 48 h of treatment.

Click to enlarge
Rating
Source Invest New Drugs , 2010, 30, 417-422. Dasatinib purchased from Selleck
Method phospho-kinase array analysis
Cell Lines EHEB (p53wt) cell lines, BJAB (p53mut) B cell lines
Concentrations
Incubation Time 24 h
Results As shown in Fig. a , the most evident effects of Dasatinib in both cell models were represented by a significant down-regulation of the phosphorylation levels of p38 MAPK, ERK1/2 and CREB. In addition, densitometric analysis of the phospho-kinase array demonstrated that Dasatinib also inhibited the phosphorylation levels of several STAT family members (STAT1, STAT2, STAT3, STAT5a/b and STAT6), the most evident effect in both p53 wild-type (EHEB) and p53 mutated (BJAB) cell lines being on STAT2, STAT3 and STAT6 (Fig. b)

Click to enlarge
Rating
Source Invest New Drugs , 2010, 30, 417-422. Dasatinib purchased from Selleck
Method Western blot
Cell Lines p53wild-type(EHEB, JVM-2) cell lines, p53mutated(MEC-2, BJAB) cell lines
Concentrations 10 μM
Incubation Time 24 h
Results "Upon exposure to Dasatinib, a decrease of phosphorylated proteins was confirmed by Western blot analys is in all cell lines investigated without significant differences between p53wild-type and p53mutated cell lines.

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Rating
Source Dr. Thomas Kruwel of Fraunhofer-Institute for Toxicology and Experimental Medicine-Dasatinib (BMS-354825) purchased from Selleck. Dasatinib purchased from Selleck
Method Cell vability assays
Cell Lines A2C12, Beta D5, Gamma A3, Gamma D12, A549, CaCo2, HepG2 cell lines
Concentrations 0.001-1000 nM
Incubation Time 24/96 h
Results

文献中の引用 (61)

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description
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