Veliparib (ABT-888) 化学構造
分子量: 244.29

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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 MWfLbY5ie2ViQYPzZZk> NHvDXlE{OCCvaX6= M2n0eGlvcGmkaYTpc44hd2ZiUFHSVFEhf2m2aDDFR|UxKG:oIECuNFAzKM7:TR?= MmDGNVk5QDh5NkC=
Jurkat MWnLbY5ie2ViQYPzZZk> Mn3SPVYhcA>? MXTEUXNQ NXTvcGpVUW6qaXLpeIlwdiCxZjDQRXJROSCjc4Pld5Nm\CCjczDy[YR2[3Srb36gc4Yh[2WubDD2bYFjcWyrdImge4l1cCCHQ{WwJI9nKDNizszN MkXVNlM5PTBzOUm=
Capan1 M3TJSGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlP5O|IhcA>? MnLxSG1UVw>? M13zSWFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgRnJESTJiZ3Xu[UBufXSjdHXkJIh2dWGwIFPhdIFvOSClZXzsd{B4cXSqIFnDOVAhd2ZiM{muO{DPxE1? NGniS2YzPDN7OEO4Ny=>
DT40 MUXDfZRwfG:6aXOgRZN{[Xl? NWDNfII1PzJiaB?= MUTEUXNQ Mn:zR5l1d3SxeHnjbZR6KGGpYXnud5Qh[2irY3vlckBDWkODMj3k[YZq[2mnboSgSHQ1OCClZXzsdy=> MoHVNlQ6OjJ3OEe=
ML-1 MkDuRZBweHSxdHnjJGF{e2G7 NV3CcFFJOi53IN88US=> M4jkXlI1KGh? M3fk[GROW09? NGPCRlhUgW6ncnfpd5Rq[2GubImg[Y5p[W6lZYOgWHJCUUxvaX7keYNm\CCjcH;weI9{cXNiaX6gUWwuOSClZXzsdy=> MoDMNlQ5QTVzM{W=
HCT-116 NV7aXJZ[U2mwYYPlJGF{e2G7 M1TXeVAvPSEQvF2= NYPkeYFNOjRiaB?= NVLzR2JtWEGUUDDhZ5Rqfmm2eTDk[YNz\WG|ZYO= M3\3WFI{ODV2MkGz
UM-SCC1 MkW1R5l1d3SxeHnjJGF{e2G7 NEL4UVIyOCEQvF2= NHjQcoMzPCCq MkfzVoVlfWOnczD0bIUh[2WubDD2bYFjcWyrdIm= MUeyNVkyOjZ{MB?=
FaDu MX7DfZRwfG:6aXOgRZN{[Xl? NIjsVpAyOCEQvF2= NFrxSVIzPCCq NVXsO5Y3WmWmdXPld{B1cGViY3XscEB3cWGkaXzpeJk> NX3tXGh[OjF7MUK2NlA>
PC-3 M4[xTGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1yzclExKM7:TR?= MUHJcoR2[2W|IHGgd4lodmmoaXPhcpQhcW6qaXLpeIlwdiCrbjDjc4xwdnliZn;ycYF1cW:wwrC= NGj1R5AzOTV5MUmxNi=>
EoL-1-cell NE\CVYtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkDFTWM2OD1zLkC3PVgh|ryP MV3TRW5ITVJ?
NCI-SNU-5 M3;RZ2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Ml2yTWM2OD1|LkGyPFQyKM7:TR?= M3rmVHNCVkeHUh?=
BV-173 NXy2U2dXT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUP2VIJwUUN3ME21MlQ2PDB7IN88US=> NFy1bJZUSU6JRWK=
HCC1806 MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWPJR|UxRTVwN{WxO|Mh|ryP NX\QOHVHW0GQR1XS
COLO-680 NFz5NHRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoXkTWM2OD14LkKxOFA3KM7:TR?= MU\TRW5ITVJ?
HCC2218 M4\pNGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYHJR|UxRTdwN{m3NFQh|ryP MonSV2FPT0WU
SK-MEL-24 NX;XVolTT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mn24TWM2OD15LkixPVI1KM7:TR?= NEexZnBUSU6JRWK=
NCI-H720 NGfDflZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnTHTWM2OD16LkSzOlA{KM7:TR?= NH;RW4RUSU6JRWK=
KASUMI-1 NIj1VZlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFWwRY9KSzVyPUiuPFkzPjZizszN MUHTRW5ITVJ?
HAL-01 NHLtZoVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2rOeGlEPTB;OT64PFYzKM7:TR?= MonjV2FPT0WU
CAL-33 MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEHROotKSzVyPUGwMlQ{PCEQvF2= MoTEV2FPT0WU
SK-MEL-1 Mn;RS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoXJTWM2OD1zMj60OlY{KM7:TR?= MUfTRW5ITVJ?
Ramos-2G6-4C10 MnTCS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVjJR|UxRTF{LkS3OVIh|ryP MkfoV2FPT0WU
KY821 MlvsS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYjodlZTUUN3ME2xNk41QDVizszN MX;TRW5ITVJ?
HEC-1 NIHFPFlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWPJR|UxRTF{LkmxPVYh|ryP NUTWTWdjW0GQR1XS
SK-NEP-1 MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGTDco5KSzVyPUGzMlE3PiEQvF2= MoLNV2FPT0WU
MN-60 M16zSGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXLJR|UxRTF|LkWzPFkh|ryP NWjjUVc4W0GQR1XS
DU-145 MVfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUXXO4t7UUN3ME2xN{46ODV|IN88US=> M2SxcHNCVkeHUh?=
EW-3 NYXDNVhiT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1PUb2lEPTB;MUSuOVU3PSEQvF2= NF[3epJUSU6JRWK=
OS-RC-2 MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mn;sTWM2OD1zNT65OVg6KM7:TR?= MkfwV2FPT0WU
RPMI-8226 NY\qPHF6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHrYWplKSzVyPUG2MlIxPDJizszN NUPaNllTW0GQR1XS
ChaGo-K-1 Mm[1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mn\zTWM2OD1zNj61N|I2KM7:TR?= MmG2V2FPT0WU
DEL M3j2d2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NU\hWnhuUUN3ME2xOk43PzF5IN88US=> NInN[mZUSU6JRWK=
GP5d NHjKPJhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXXwOZF{UUN3ME2xO{4xPTNizszN NH7jNWhUSU6JRWK=
COLO-668 NGXqfoRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVzrRY9tUUN3ME2xO{43Ojl2IN88US=> NIXqVHJUSU6JRWK=
H9 M3O4ZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M33BcWlEPTB;MUiuNlg{OyEQvF2= MUfTRW5ITVJ?
NKM-1 NVXvSJc4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NV;aW|Y4UUN3ME2xPE42OTF7IN88US=> NH;4dYxUSU6JRWK=
KYSE-150 M3vnS2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYTJR|UxRTF6Lkm5PFYh|ryP NED0[mJUSU6JRWK=
Daoy MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnTHTWM2OD1zOT61OlQ6KM7:TR?= NYjMOldpW0GQR1XS
ECC10 M2LWdmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkLtTWM2OD1{MD63OFU2KM7:TR?= MXTTRW5ITVJ?
A388 NGPVNJFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVHJR|UxRTJzLkmwPVEh|ryP MVfTRW5ITVJ?
MHH-NB-11 M4LlO2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3\S[WlEPTB;MkOuNVM3OyEQvF2= MnzkV2FPT0WU
HCC1937 MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1rFTmlEPTB;MkSuO|Q3KM7:TR?= MYTTRW5ITVJ?
TGBC11TKB NYjOeVNqT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFnTeY1KSzVyPUK1MlY5PjNizszN NIm2em9USU6JRWK=
CTV-1 M2nNXmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHG1PYpKSzVyPUK1Mlg6PjlizszN NEi4SYVUSU6JRWK=
NCI-H2029 NV;Z[Ws{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mor5TWM2OD1{Nj60NlM5KM7:TR?= NXS2U5diW0GQR1XS
HLE NGHEbYJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXzJR|UxRTJ5LkC1OEDPxE1? M{TXfXNCVkeHUh?=
NCI-H1693 M2r3cmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIDRNWhKSzVyPUK3MlI5QThizszN NF:0fFlUSU6JRWK=
HCC70 NX35TpFGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHPUbW5KSzVyPUK3MlczPDZizszN NYjX[4F5W0GQR1XS
BEN NF7JRWJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXHJR|UxRTJ5Lkm1OlYh|ryP NFL2N29USU6JRWK=
LB771 MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEnpbZdKSzVyPUK4Mlg{PzNizszN M2\jdnNCVkeHUh?=
697 NX30PVdyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MljtTWM2OD1{OT6wNlM2KM7:TR?= MoPJV2FPT0WU
LU-139 NHewR3pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHSxVoJKSzVyPUK5MlM4PDhizszN M1TPVHNCVkeHUh?=
EW-13 M4XVemdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkjjTWM2OD1{OT6zPFE1KM7:TR?= M1fXRnNCVkeHUh?=
MOLT-13 NWX0VpFkT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1HTdGlEPTB;MkmuN|gyPCEQvF2= MWjTRW5ITVJ?
L-363 Ml7yS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkKwTWM2OD1{OT60O|k5KM7:TR?= MYjTRW5ITVJ?
EM-2 NX;2fGNOT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{Xrc2lEPTB;MkmuOFkxOSEQvF2= NHjqb|NUSU6JRWK=
RS4-11 NEDwWnBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MV3JR|UxRTNyLkSyOFEh|ryP NEHjcmVUSU6JRWK=
A2780 MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NE\vU3lKSzVyPUOwMlc1PTdizszN MoTSV2FPT0WU
KU812 M1TMRWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXPDXGVKUUN3ME2zNk4{PjR{IN88US=> MmjWV2FPT0WU
COLO-684 NGLn[YRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1;IdWlEPTB;M{OuN|U6QSEQvF2= M{TqUnNCVkeHUh?=
MFE-280 NUHWUXFlT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MljKTWM2OD1|Mz6zPFg6KM7:TR?= M1;rfHNCVkeHUh?=
KG-1 MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVzJR|UxRTN|Lk[wNFEh|ryP NGTxV41USU6JRWK=
JVM-3 MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXzJR|UxRTN3LkW4Olgh|ryP NFvONY1USU6JRWK=
MV-4-11 M3jwTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVfzXHlnUUN3ME2zOU45PDl7IN88US=> M17He3NCVkeHUh?=
LAMA-84 NXLoVJNpT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1;reGlEPTB;M{[uO|M1PSEQvF2= NYfLTldTW0GQR1XS
MOLT-16 NWXk[XNiT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{DPT2lEPTB;M{[uPVUzKM7:TR?= M1nPN3NCVkeHUh?=
H4 MljKS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFrGN2xKSzVyPUO3MlU3PyEQvF2= NIjGZ2hUSU6JRWK=
T47D MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYHJR|UxRTN5LkewNVgh|ryP NWDnbYI4W0GQR1XS
CAL-54 M1\5S2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2jpPWlEPTB;M{euPVY3KM7:TR?= Mlu2V2FPT0WU
SW982 M3W4[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3LGemlEPTB;M{iuNFk6QCEQvF2= NVz4XXZKW0GQR1XS
IGROV-1 NVXqfWtLT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mn7rTWM2OD1|OT6zN|A1KM7:TR?= NHfOVHRUSU6JRWK=
NB14 MlPZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWXJR|UxRTRyLkewN|Eh|ryP MkHxV2FPT0WU
HCC1187 Mlu4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVHTOGg6UUN3ME20NU4zPzdzIN88US=> NUXyOYhjW0GQR1XS
SBC-1 M{K3OWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFvWV5pKSzVyPUSxMlMxPjNizszN MkC2V2FPT0WU
KARPAS-45 NUjub3NPT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHr3UWJKSzVyPUSxMlQ5OThizszN M{n0bnNCVkeHUh?=
MOLT-4 M4LCUmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NV3zSmR4UUN3ME20Nk4zPTN6IN88US=> M1PhO3NCVkeHUh?=
JVM-2 M1\mbGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVrNN5d7UUN3ME20Nk46OjB5IN88US=> NF7Mc4VUSU6JRWK=
A4-Fuk NYe0UY1uT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MY\JR|UxRTR|LkW2PVEh|ryP NVjZW|Z6W0GQR1XS
MDA-MB-361 MXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYPPOpFSUUN3ME20N{45PDF2IN88US=> MX\TRW5ITVJ?
BALL-1 M{D0XWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWPqcYFpUUN3ME20N{46PTN{IN88US=> NUXSXZgyW0GQR1XS
T98G NX7hN5hyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NULxWHZ1UUN3ME20OE45PTF5IN88US=> MoqzV2FPT0WU
Mo-T MlvYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NX3nNpB[UUN3ME20OU43Ozh7IN88US=> MmLtV2FPT0WU
MHH-PREB-1 MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mn6wTWM2OD12NT63OVg2KM7:TR?= NILTT4VUSU6JRWK=
ALL-PO MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1;BfWlEPTB;NEeuN|c6OSEQvF2= MkPqV2FPT0WU
NCI-H510A MkPxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXzJR|UxRTR5LkmwN|Qh|ryP MnnYV2FPT0WU
ML-2 NVvCbW1sT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3XvPWlEPTB;NEmuO|g2PiEQvF2= NEXhTFlUSU6JRWK=

... 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 3年-20℃
2年-80℃in solvent
別名 NSC 737664
溶解度 (25°C) * In vitro DMSO 17 mg/mL (69.58 mM)
Water <1 mg/mL
Ethanol <1 mg/mL
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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    Talazoparib (BMN 673)は、新しい PARP 阻害剤で、IC50 が 0.58 nMです。

    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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