Veliparib (ABT-888) 化学構造
分子量: 244.29

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Quality Control & MSDS

製品説明

  • Compare PARP Inhibitors
    PARP製品生物活性の比較
  • 研究分野
  • Combination Therapy
    併用療法
  • Veliparib (ABT-888)のメカニズム

製品の説明

生物活性

製品説明 Veliparib (ABT-888)は、PARP1PARP2の強力な阻害剤で、Kiがそれぞれ 5.2 nM と 2.9 nMになる。
ターゲット

PARP1

PARP2

IC50

5.2 nM (Ki)

2.9 nM (Ki) [1]

In vitro試験 ABT-888 is inactive to SIRT2 (>5 μM). [1] ABT-888 inhibits the PARP activity with EC50 of 2 nM in C41 cells. [2] ABT-888 could decrease the PAR levels in both irradiated and nonirradiated H460 cells. ABT-888 also reduces clonogenic survival and inhibits DNA repair by PARP-1 inhibition in H460 cells. ABT-888 increases apoptosis and autophagy in H460 cells when combination with radiation. [3] ABT-888 also inhibits PARP activity in H1299, DU145 and 22RV1 cells and the inhibition is independent of p53 function. ABT-888 (10 μM) suppresses the surviving fraction (SF) by 43% in the clonogenic H1299 cells. ABT-888 shows effective radiosensitivity in oxic H1299 cells. Furthermore, ABT-888 could attenuate the SF of hypoxic-irradiated cells including H1299, DU145 and 22RV1. [4]
Cell Data
Cell LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
C41 NFnmbW1McW6jc3WgRZN{[Xl? NF:xe4g{OCCvaX6= M3Wz[WlvcGmkaYTpc44hd2ZiUFHSVFEhf2m2aDDFR|UxKG:oIECuNFAzKM7:TR?= NV;rRlA6OTl6OEi3OlA>
Jurkat NFjScplMcW6jc3WgRZN{[Xl? M3S5NFk3KGh? MVHEUXNQ MWLJcohq[mm2aX;uJI9nKFCDUmCxJIF{e2W|c3XkJIF{KHKnZIXjeIlwdiCxZjDj[YxtKH[rYXLpcIl1gSC5aYToJGVEPTBib3[gN{DPxE1? MmHBNlM5PTBzOUm=
Capan1 MYrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXS3NkBp M1\WbmROW09? MVPBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IFLSR2EzKGenbnWgcZV1[XSnZDDoeY1idiCFYYDhclEh[2WubIOge4l1cCCLQ{WwJI9nKDN7Lkeg{txO NFS2dmEzPDN7OEO4Ny=>
DT40 MY\DfZRwfG:6aXOgRZN{[Xl? MkT1O|IhcA>? NUHDTZlpTE2VTx?= MW\DfZRwfG:6aXPpeJkh[WejaX7zeEBkcGmla3XuJGJTS0F{LXTl[olkcWWwdDDEWFQxKGOnbHzz NHexR4czPDl{MkW4Oy=>
ML-1 MXfBdI9xfG:2aXOgRZN{[Xl? MoPDNk42KM7:TR?= NFrr[W4zPCCq Mmq4SG1UVw>? M{fLZXN6dmW{Z3nzeIlk[WyueTDlcohidmOnczDUVmFKVC2rbnT1Z4VlKGGyb4D0c5NqeyCrbjDNUE0yKGOnbHzz MUKyOFg6PTF|NR?=
HCT-116 NGfiWoJMcW6jc3WgRZN{[Xl? NYrNfXhXOC53IN88US=> MXWyOEBp Mli1VGFTWCCjY4Tpeol1gSCmZXPy[YF{\XN? M2fTcVI{ODV2MkGz
UM-SCC1 NHvSPWREgXSxdH;4bYMhSXO|YYm= Mm\DNVAh|ryP MlzTNlQhcA>? MU\S[YR2[2W|IITo[UBk\WyuII\pZYJqdGm2eR?= NG[x[3QzOTlzMk[yNC=>
FaDu MXrDfZRwfG:6aXOgRZN{[Xl? MW[xNEDPxE1? MWiyOEBp NF33V|lT\WS3Y3XzJJRp\SClZXzsJJZq[WKrbHn0fS=> NWfGOlVqOjF7MUK2NlA>
PC-3 MnjVS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NF7XeFYyOCEQvF2= MnrtTY5lfWOnczDhJJNq\26rZnnjZY51KGmwaHnibZRqd25iaX6gZ49td267IH\vdo1ifGmxbtMg M{TBPFIyPTdzOUGy
EoL-1-cell NVXzTYFLT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXTuZ|d5UUN3ME2xMlA4QThizszN NGP3ZWlUSU6JRWK=
NCI-SNU-5 Mnv0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2Hl[GlEPTB;Mz6xNlg1OSEQvF2= NHXWZW9USU6JRWK=
BV-173 MljrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlSzTWM2OD13LkS1OFA6KM7:TR?= MnK4V2FPT0WU
HCC1806 NETS[FNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUnHVohoUUN3ME21Mlc2OTd|IN88US=> Mo\uV2FPT0WU
COLO-680 MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHm1W5dKSzVyPU[uNlE1ODZizszN M3fGbnNCVkeHUh?=
HCC2218 MYDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoDETWM2OD15Lke5O|A1KM7:TR?= NUXzbHNzW0GQR1XS
SK-MEL-24 NYjOTGRXT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVP3ZVk6UUN3ME23MlgyQTJ2IN88US=> NXryNG0{W0GQR1XS
NCI-H720 M1vLXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYHJR|UxRThwNEO2NFMh|ryP Ml7lV2FPT0WU
KASUMI-1 NHfndFRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXfJR|UxRThwOEmyOlYh|ryP MXLTRW5ITVJ?
HAL-01 NGf5d5ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFnOXnFKSzVyPUmuPFg3OiEQvF2= NYTyOJE3W0GQR1XS
CAL-33 MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX\mdmZPUUN3ME2xNE41OzRizszN M2Pmd3NCVkeHUh?=
SK-MEL-1 NWGzfGh1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlzBTWM2OD1zMj60OlY{KM7:TR?= MlWxV2FPT0WU
Ramos-2G6-4C10 NH;JU5JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmfKTWM2OD1zMj60O|UzKM7:TR?= NXqwW3FOW0GQR1XS
KY821 NIXVSphIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWDJR|UxRTF{LkS4OUDPxE1? M2foeXNCVkeHUh?=
HEC-1 MVfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWjqNpBUUUN3ME2xNk46OTl4IN88US=> M1\T[XNCVkeHUh?=
SK-NEP-1 NWPiPFB1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M321dGlEPTB;MUOuNVY3KM7:TR?= NFXwc49USU6JRWK=
MN-60 MmDnS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXXJR|UxRTF|LkWzPFkh|ryP MVvTRW5ITVJ?
DU-145 MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NH\qc25KSzVyPUGzMlkxPTNizszN M{j2XHNCVkeHUh?=
EW-3 MlLVS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYTufFh3UUN3ME2xOE42PTZ3IN88US=> NUDVXYpLW0GQR1XS
OS-RC-2 Mnu3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlLYTWM2OD1zNT65OVg6KM7:TR?= NYOxZYUxW0GQR1XS
RPMI-8226 NFWySI1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHLXc3JKSzVyPUG2MlIxPDJizszN NFrrO49USU6JRWK=
ChaGo-K-1 NU\WVmxlT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHPwPJhKSzVyPUG2MlU{OjVizszN M4\VRXNCVkeHUh?=
DEL NIrXdHNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIDGT4FKSzVyPUG2MlY4OTdizszN NX3DeZIxW0GQR1XS
GP5d MmLnS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4DBVmlEPTB;MUeuNFU{KM7:TR?= MmLsV2FPT0WU
COLO-668 M2rPOGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEPBeY5KSzVyPUG3MlYzQTRizszN Mo\mV2FPT0WU
H9 MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MX\JR|UxRTF6LkK4N|Mh|ryP MoP2V2FPT0WU
NKM-1 NFvWWIdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYPJR|UxRTF6LkWxNVkh|ryP M1PsN3NCVkeHUh?=
KYSE-150 M33Wcmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{K1R2lEPTB;MUiuPVk5PiEQvF2= M1\qWHNCVkeHUh?=
Daoy NYTYd4NmT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYTVdJZuUUN3ME2xPU42PjR7IN88US=> M2DW[XNCVkeHUh?=
ECC10 NXLPT|VvT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MULJR|UxRTJyLke0OVUh|ryP MmLmV2FPT0WU
A388 NEXwZmlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MV7JR|UxRTJzLkmwPVEh|ryP M3ix[3NCVkeHUh?=
MHH-NB-11 MXfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX;RNGR3UUN3ME2yN{4yOzZ|IN88US=> MX7TRW5ITVJ?
HCC1937 NFrnc5hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{fyN2lEPTB;MkSuO|Q3KM7:TR?= NWDUV25IW0GQR1XS
TGBC11TKB NU\ycGx4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGDKNYpKSzVyPUK1MlY5PjNizszN MmTmV2FPT0WU
CTV-1 M4XHR2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFvZboRKSzVyPUK1Mlg6PjlizszN NU\2XmJ[W0GQR1XS
NCI-H2029 M3nwOWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlfvTWM2OD1{Nj60NlM5KM7:TR?= M3Xqb3NCVkeHUh?=
HLE M4n3TWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnX3TWM2OD1{Nz6wOVQh|ryP M3\VUnNCVkeHUh?=
NCI-H1693 MnizS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MX3JR|UxRTJ5LkK4PVgh|ryP NH;CcohUSU6JRWK=
HCC70 NGr1T2pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWrSWo5SUUN3ME2yO{44OjR4IN88US=> NXzyRnNwW0GQR1XS
BEN MlSwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4O3b2lEPTB;MkeuPVU3PiEQvF2= NHTzVI9USU6JRWK=
LB771 NWjoZlBPT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkfUTWM2OD1{OD64N|c{KM7:TR?= NU\GW|Z{W0GQR1XS
697 NFi0fWRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUjJR|UxRTJ7LkCyN|Uh|ryP NH7adVlUSU6JRWK=
LU-139 M4ewWmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHzvSY9KSzVyPUK5MlM4PDhizszN MXjTRW5ITVJ?
EW-13 NHXTOHpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MX7JR|UxRTJ7LkO4NVQh|ryP NYLkNpBlW0GQR1XS
MOLT-13 NHz6S3VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1vMOWlEPTB;MkmuN|gyPCEQvF2= MlHKV2FPT0WU
L-363 M1HEbWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnHJTWM2OD1{OT60O|k5KM7:TR?= NW\STXpUW0GQR1XS
EM-2 NXzIOYk{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkToTWM2OD1{OT60PVAyKM7:TR?= MVPTRW5ITVJ?
RS4-11 M4DOSGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MknlTWM2OD1|MD60NlQyKM7:TR?= MY\TRW5ITVJ?
A2780 MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX7IdWZnUUN3ME2zNE44PDV5IN88US=> MYXTRW5ITVJ?
KU812 NFjZZ5VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MY\JR|UxRTN{LkO2OFIh|ryP MVrTRW5ITVJ?
COLO-684 MXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3voOGlEPTB;M{OuN|U6QSEQvF2= NF;Nd|BUSU6JRWK=
MFE-280 MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{fJbGlEPTB;M{OuN|g5QSEQvF2= MVzTRW5ITVJ?
KG-1 NID4fo5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYnJR|UxRTN|Lk[wNFEh|ryP NHrlVodUSU6JRWK=
JVM-3 M{jic2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVjJR|UxRTN3LkW4Olgh|ryP NHjZbINUSU6JRWK=
MV-4-11 NGnpTY5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3rvfGlEPTB;M{WuPFQ6QSEQvF2= NWPtRnFYW0GQR1XS
LAMA-84 MWXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVjXR5RDUUN3ME2zOk44OzR3IN88US=> NGDkfoFUSU6JRWK=
MOLT-16 M3KzcWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYDROWxEUUN3ME2zOk46PTJizszN NXzoSVFDW0GQR1XS
H4 NVP1[VlZT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIXOeJBKSzVyPUO3MlU3PyEQvF2= M{W1VHNCVkeHUh?=
T47D NUDwSllZT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXvpc5JtUUN3ME2zO{44ODF6IN88US=> M4fFcXNCVkeHUh?=
CAL-54 M2P6VWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXvJR|UxRTN5Lkm2OkDPxE1? M4q4bXNCVkeHUh?=
SW982 NFjINGtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NV\abWpLUUN3ME2zPE4xQTl6IN88US=> MXTTRW5ITVJ?
IGROV-1 NWXn[|UzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEPLeGVKSzVyPUO5MlM{ODRizszN M{PQPHNCVkeHUh?=
NB14 MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUnJR|UxRTRyLkewN|Eh|ryP MV3TRW5ITVJ?
HCC1187 NWm0TXJqT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYfWPGhPUUN3ME20NU4zPzdzIN88US=> M4rDR3NCVkeHUh?=
SBC-1 NVT4fYh6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1\vUmlEPTB;NEGuN|A3OyEQvF2= Moq1V2FPT0WU
KARPAS-45 MlnvS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkHnTWM2OD12MT60PFE5KM7:TR?= MmXvV2FPT0WU
MOLT-4 NWXwW4dlT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Ml76TWM2OD12Mj6yOVM5KM7:TR?= MXPTRW5ITVJ?
JVM-2 MX3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkLTTWM2OD12Mj65NlA4KM7:TR?= MUjTRW5ITVJ?
A4-Fuk NHHpR5hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NH7PS4FKSzVyPUSzMlU3QTFizszN NFHwSYpUSU6JRWK=
MDA-MB-361 MYLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVu1WIl7UUN3ME20N{45PDF2IN88US=> NFrNbZlUSU6JRWK=
BALL-1 NYnsdWR1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoHiTWM2OD12Mz65OVMzKM7:TR?= MVnTRW5ITVJ?
T98G NHrFS2xIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWT3Rpp1UUN3ME20OE45PTF5IN88US=> NGnCeFVUSU6JRWK=
Mo-T M1rWXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoTaTWM2OD12NT62N|g6KM7:TR?= MofjV2FPT0WU
MHH-PREB-1 M{fuWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3TNfmlEPTB;NEWuO|U5PSEQvF2= MWPTRW5ITVJ?
ALL-PO MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkDxTWM2OD12Nz6zO|kyKM7:TR?= NYLOcoJLW0GQR1XS
NCI-H510A MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUXJR|UxRTR5LkmwN|Qh|ryP NHLCUIlUSU6JRWK=
ML-2 M2DPc2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2KwWWlEPTB;NEmuO|g2PiEQvF2= NWrVPXdxW0GQR1XS

... Click to View More Cell Line Experimental Data

In vivo試験 The oral bioavailability of ABT-888 is 56%-92% in mice, Sprague-Dawley rats, beagle dogs, and cynomolgus monkeys after oral administration. [1] ABT-888 (25 mg/kg i.p.) could improve tumor growth delay in a NCI-H460 xenograft model with well tolerated. Combination with radiation, ABT-888 decreases the tumor vessel formation. [3] ABT-888 reduces intratumor PAR levels by more than 95% at a dose of 3 and 12.5 mg/kg in A375 and Colo829 xenograft models and the suppression could be maintained over time. [4]
臨床試験 A Phase I study of evaluating the bioavailability and food effect of three formulations of ABT-888 on pharmacokinetics in subjects with solid tumors has been completed.
特集 Increases the efficacy of common cancer therapies such as radiation and alkylating agents.

プロトコル (参考用のみ)

キナーゼアッセイ:

[1]

In vitro PARP assays PARP assays are conducted in a buffer containing 50 mM Tris (pH 8.0), 1 mM DTT, 1.5 μM [3H]NAD+ (1.6 μCi/mmol), 200 nM biotinylated histone H1, 200 nM slDNA, and 1 nM PARP-1 or 4 nM PARP-2 enzyme. Reactions are terminated with 1.5 mM benzamide, transferred to streptavidin Flash plates, and counted using a TopCount microplate scintillation counter.

動物実験:

[1]

動物モデル NCI-H460, H460, B16F10 and 9L xenografts in C57BL/6 mice
製剤 Formulated in solution containing 0.9% NaCl adjusted to pH 4.0
投薬量 ~25 mg/kg
投与方法 Orally administered

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 Veliparib (ABT-888) SDF
分子量 244.29
化学式

C13H16N4O

CAS No. 912444-00-9
保管 2年-20℃
6月-80℃in solvent
別名 NSC 737664
溶解度 (25°C) * In vitro DMSO 17 mg/mL (69.58 mM)
<1 mg/mL (<1 mM)
エタノール <1 mg/mL (<1 mM)
In vivo 0.5% methylcellulose+0.2% Tween 80 5 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 (R)-2-(2-methylpyrrolidin-2-yl)-1H-benzo[d]imidazole-4-carboxamide

文献中の引用 (39)

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    Features:Most potent and selective PARPi reported thus far.

  • Iniparib (BSI-201)

    Iniparib (BSI-201)は、推定のPoly(ADPリボース)ポリメラーゼ(PARP I)阻害剤です

  • PJ34 HCl

    PJ34 HCl is the hydrochloride salt of PJ34, which is a PARP inhibitor with EC50 of 20 nM and is equally potent to PARP1/2.

    Features:Water-soluble PARP1/2 inhibitor with >10,000-fold potentcy vs. 3-aminobenzamide (prototypical PARP inhibitor). Potential uses in cardiovascular diseases (stroke, cerebral ischemia, & myocardial ischemia).

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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