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 NEDtfZlMcW6jc3WgRZN{[Xl? NWXZeVhzOzBibXnu MXTJcohq[mm2aX;uJI9nKFCDUmCxJJdqfGhiRVO1NEBw\iByLkCwNkDPxE1? NYPTSoV7OTl6OEi3OlA>
Jurkat Mmj0T4lv[XOnIFHzd4F6 MkDaPVYhcA>? MUjEUXNQ NXPsWnJ7UW6qaXLpeIlwdiCxZjDQRXJROSCjc4Pld5Nm\CCjczDy[YR2[3Srb36gc4Yh[2WubDD2bYFjcWyrdImge4l1cCCHQ{WwJI9nKDNizszN NUDSUIRMOjN6NUCxPVk>
Capan1 NIXITG9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M165RlczKGh? NGe3c21FVVOR MWrBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IFLSR2EzKGenbnWgcZV1[XSnZDDoeY1idiCFYYDhclEh[2WubIOge4l1cCCLQ{WwJI9nKDN7Lkeg{txO NInLTmozPDN7OEO4Ny=>
DT40 MVfDfZRwfG:6aXOgRZN{[Xl? M3\TVlczKGh? M13kcmROW09? Mk\jR5l1d3SxeHnjbZR6KGGpYXnud5Qh[2irY3vlckBDWkODMj3k[YZq[2mnboSgSHQ1OCClZXzsdy=> NWXkcnpoOjR7MkK1PFc>
ML-1 NHrwTlNCeG:ydH;0bYMhSXO|YYm= MofCNk42KM7:TR?= MmDQNlQhcA>? MX;EUXNQ NWjIZmJwW3mwZYLnbZN1cWOjbHz5JIVvcGGwY3XzJHRTSUmOLXnu[JVk\WRiYYDvdJRwe2m|IHnuJG1NNTFiY3XscJM> M{TtVVI1QDl3MUO1
HCT-116 MVPLbY5ie2ViQYPzZZk> MWOwMlUh|ryP NGW5TYwzPCCq M2HJdHBCWlBiYXP0bZZqfHliZHXjdoVie2W| NWT5eY9rOjNyNUSyNVM>
UM-SCC1 M4DUWGN6fG:2b4jpZ{BCe3OjeR?= NHfVc3IyOCEQvF2= NEfBdIwzPCCq NF7TZmtT\WS3Y3XzJJRp\SClZXzsJJZq[WKrbHn0fS=> MmDoNlE6OTJ4MkC=
FaDu M1:xOmN6fG:2b4jpZ{BCe3OjeR?= MUexNEDPxE1? MUiyOEBp NETnWmJT\WS3Y3XzJJRp\SClZXzsJJZq[WKrbHn0fS=> MWWyNVkyOjZ{MB?=
PC-3 MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUnwb5N2OTBizszN M1\FSWlv\HWlZYOgZUB{cWewaX\pZ4FvfCCrbnjpZol1cW:wIHnuJINwdG:weTDmc5Ju[XSrb39CpC=> NULieWpDOjF3N{G5NVI>
EoL-1-cell NW\1WVc{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{iwSGlEPTB;MT6wO|k5KM7:TR?= MlHrV2FPT0WU
NCI-SNU-5 NEHIUWNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGniNGNKSzVyPUOuNVI5PDFizszN NETXR|dUSU6JRWK=
BV-173 NFryTJJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1fUd2lEPTB;NT60OVQxQSEQvF2= M{C2VXNCVkeHUh?=
HCC1806 MnrqS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MY\JR|UxRTVwN{WxO|Mh|ryP NYPK[4d2W0GQR1XS
COLO-680 NEfLZW5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUPJR|UxRTZwMkG0NFYh|ryP M3\5XnNCVkeHUh?=
HCC2218 NYGyV5FUT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH7zVnRKSzVyPUeuO|k4ODRizszN NUfGSpVqW0GQR1XS
SK-MEL-24 M3ryc2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2rMfmlEPTB;Nz64NVkzPCEQvF2= Mn3YV2FPT0WU
NCI-H720 MlvPS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NX;Uc29sUUN3ME24MlQ{PjB|IN88US=> MYXTRW5ITVJ?
KASUMI-1 NFGwZYZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEnxXY5KSzVyPUiuPFkzPjZizszN MmrEV2FPT0WU
HAL-01 M4fzTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NF\QUJNKSzVyPUmuPFg3OiEQvF2= NETLdlZUSU6JRWK=
CAL-33 MnXjS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MojoTWM2OD1zMD60N|Qh|ryP NHK0fnNUSU6JRWK=
SK-MEL-1 MlH0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFGzOGtKSzVyPUGyMlQ3PjNizszN MX;TRW5ITVJ?
Ramos-2G6-4C10 NHHpTIdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmLmTWM2OD1zMj60O|UzKM7:TR?= MXfTRW5ITVJ?
KY821 M3fXRmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlXjTWM2OD1zMj60PFUh|ryP M3T0SHNCVkeHUh?=
HEC-1 MV3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVXJR|UxRTF{LkmxPVYh|ryP NEDnV4RUSU6JRWK=
SK-NEP-1 M17NXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUj5dlZJUUN3ME2xN{4yPjZizszN NV7SXohuW0GQR1XS
MN-60 MlrZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXv3VHF7UUN3ME2xN{42Ozh7IN88US=> M{XPfnNCVkeHUh?=
DU-145 MVnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mn3rTWM2OD1zMz65NFU{KM7:TR?= MmrUV2FPT0WU
EW-3 NXvoSox4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWnyNFFrUUN3ME2xOE42PTZ3IN88US=> NVfYO2ZDW0GQR1XS
OS-RC-2 MonqS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlnqTWM2OD1zNT65OVg6KM7:TR?= M3W4SnNCVkeHUh?=
RPMI-8226 NGO5U2tIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NV7aSHB6UUN3ME2xOk4zODR{IN88US=> MXvTRW5ITVJ?
ChaGo-K-1 Mn:yS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1yyS2lEPTB;MU[uOVMzPSEQvF2= MlSxV2FPT0WU
DEL MoP6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXPJR|UxRTF4Lk[3NVch|ryP M1TCVnNCVkeHUh?=
GP5d NHjxO5JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUTpPGRRUUN3ME2xO{4xPTNizszN MWXTRW5ITVJ?
COLO-668 MlH4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4PO[WlEPTB;MUeuOlI6PCEQvF2= NULxUGxSW0GQR1XS
H9 MX3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoLITWM2OD1zOD6yPFM{KM7:TR?= MnXXV2FPT0WU
NKM-1 NVrpbY9kT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NU\EeoxRUUN3ME2xPE42OTF7IN88US=> M125dXNCVkeHUh?=
KYSE-150 NF[3bIVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnHNTWM2OD1zOD65PVg3KM7:TR?= NWG0dGtCW0GQR1XS
Daoy M4fSNmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MV7JR|UxRTF7LkW2OFkh|ryP NWDHTHI5W0GQR1XS
ECC10 M3GwS2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEH1TGdKSzVyPUKwMlc1PTVizszN NYHie|d4W0GQR1XS
A388 M1\Ic2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MV3JR|UxRTJzLkmwPVEh|ryP NX7RSXNEW0GQR1XS
MHH-NB-11 Mn7SS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnTMTWM2OD1{Mz6xN|Y{KM7:TR?= NVrKb5YyW0GQR1XS
HCC1937 NIHiN5hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M37neWlEPTB;MkSuO|Q3KM7:TR?= MU\TRW5ITVJ?
TGBC11TKB MUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MU\JR|UxRTJ3Lk[4OlMh|ryP MmfNV2FPT0WU
CTV-1 NUDmZYJqT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NV70c5hGUUN3ME2yOU45QTZ7IN88US=> NETjd|FUSU6JRWK=
NCI-H2029 MkTvS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NE\xNJBKSzVyPUK2MlQzOzhizszN NVfiSZVjW0GQR1XS
HLE NU\C[JhCT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVHJR|UxRTJ5LkC1OEDPxE1? MWXTRW5ITVJ?
NCI-H1693 MlvVS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWnncFZoUUN3ME2yO{4zQDl6IN88US=> NEjCfI1USU6JRWK=
HCC70 Ml3pS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{X6XWlEPTB;MkeuO|I1PiEQvF2= NUnSU4FrW0GQR1XS
BEN MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MV3JR|UxRTJ5Lkm1OlYh|ryP NWnQcpZKW0GQR1XS
LB771 MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVL0Wm9VUUN3ME2yPE45Ozd|IN88US=> NGnYOZJUSU6JRWK=
697 M3HsZmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NF;OZm5KSzVyPUK5MlAzOzVizszN NWf6bndzW0GQR1XS
LU-139 NVjBZ2o1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MorLTWM2OD1{OT6zO|Q5KM7:TR?= NWO0S4FRW0GQR1XS
EW-13 M4G3Umdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NE\kXWVKSzVyPUK5MlM5OTRizszN M3;jXXNCVkeHUh?=
MOLT-13 NFvacoNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXLXbnFNUUN3ME2yPU4{QDF2IN88US=> NYDmO444W0GQR1XS
L-363 MYrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnSyTWM2OD1{OT60O|k5KM7:TR?= NIThfYFUSU6JRWK=
EM-2 MkTkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVT3fHR1UUN3ME2yPU41QTBzIN88US=> NIi0fJhUSU6JRWK=
RS4-11 NYT3VGNvT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{\JfGlEPTB;M{CuOFI1OSEQvF2= NHjPN25USU6JRWK=
A2780 M2jqdGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmPBTWM2OD1|MD63OFU4KM7:TR?= NHPubZBUSU6JRWK=
KU812 MlX4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVnJR|UxRTN{LkO2OFIh|ryP M3H4d3NCVkeHUh?=
COLO-684 NELsOIxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXzJR|UxRTN|LkO1PVkh|ryP M1XzcXNCVkeHUh?=
MFE-280 MlTpS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2r1bGlEPTB;M{OuN|g5QSEQvF2= M3vOdnNCVkeHUh?=
KG-1 M4fIeWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlHNTWM2OD1|Mz62NFAyKM7:TR?= M2HLT3NCVkeHUh?=
JVM-3 M17m[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3nXNmlEPTB;M{WuOVg3QCEQvF2= MWXTRW5ITVJ?
MV-4-11 NEHoZmtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVjJR|UxRTN3Lki0PVkh|ryP NXW1bVYxW0GQR1XS
LAMA-84 NGjoeZNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmL1TWM2OD1|Nj63N|Q2KM7:TR?= NVfhU3JIW0GQR1XS
MOLT-16 NVTuTox2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVXJR|UxRTN4Lkm1NkDPxE1? NUTBV4J5W0GQR1XS
H4 NIPzc5FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYfJR|UxRTN5LkW2O{DPxE1? Mn7uV2FPT0WU
T47D NFrTR4FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{PwSmlEPTB;M{euO|AyQCEQvF2= MXjTRW5ITVJ?
CAL-54 M1PMfmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXHkcYtMUUN3ME2zO{46PjZizszN NFHnUIxUSU6JRWK=
SW982 M2DlTWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MX;JR|UxRTN6LkC5PVgh|ryP M3Ha[HNCVkeHUh?=
IGROV-1 M3TWcGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M17s[GlEPTB;M{muN|MxPCEQvF2= MnjlV2FPT0WU
NB14 MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEToXFhKSzVyPUSwMlcxOzFizszN M1fMZXNCVkeHUh?=
HCC1187 NWP6OIpFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGrKOGlKSzVyPUSxMlI4PzFizszN M1j5UHNCVkeHUh?=
SBC-1 Mo\vS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnTNTWM2OD12MT6zNFY{KM7:TR?= MonsV2FPT0WU
KARPAS-45 M4rEcmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4e2TGlEPTB;NEGuOFgyQCEQvF2= NXzuNmszW0GQR1XS
MOLT-4 MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVnmeo9EUUN3ME20Nk4zPTN6IN88US=> MknWV2FPT0WU
JVM-2 NV;rW3RoT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3Tpc2lEPTB;NEKuPVIxPyEQvF2= NGP0fZdUSU6JRWK=
A4-Fuk M4HMZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1\Ne2lEPTB;NEOuOVY6OSEQvF2= MoHVV2FPT0WU
MDA-MB-361 NXnGZ4NpT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUP2[5MxUUN3ME20N{45PDF2IN88US=> NU\YNXA2W0GQR1XS
BALL-1 M2\pOmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGKxeHdKSzVyPUSzMlk2OzJizszN NXX5dnRoW0GQR1XS
T98G M1;WTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnqxTWM2OD12ND64OVE4KM7:TR?= M2TZfXNCVkeHUh?=
Mo-T MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFrxN4tKSzVyPUS1MlY{QDlizszN M1HTbXNCVkeHUh?=
MHH-PREB-1 M2m3XGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVPJR|UxRTR3Lke1PFUh|ryP MWTTRW5ITVJ?
ALL-PO MoHhS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYfJR|UxRTR5LkO3PVEh|ryP MVvTRW5ITVJ?
NCI-H510A MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1rjcmlEPTB;NEeuPVA{PCEQvF2= M2LLWXNCVkeHUh?=
ML-2 NEDQNYVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFvhW|NKSzVyPUS5Mlc5PTZizszN MVPTRW5ITVJ?

... 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 (38)

技術サポート&よくある質問(FAQ)

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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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