Rucaparib (AG-014699,PF-01367338) phosphate


Rucaparib (AG-014699,PF-01367338) phosphate化学構造


Rucaparib (AG-014699, PF-01367338)は一種のPARP阻害剤で、無細胞試験でPARP1に作用する時のKi値が1.4 nMになって、残り8つPARPドメインにも結合親和力を表します。臨床3期。

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  • For anchorage dependent clonogenic assays, HER2+ breast cancer BT474 cells were seeded at low density in 6-well plates and allowed to adhere overnight. The next day, olaparib and rucaparib were added at the indicated concentrations. Media and drugs were replenished every three days. After 10-15 days, depending on cell proliferation rate, cells were fixed and stained with crystal violet. Images and graphs indicate the results compared to control condition. Data are mean ± S.D. n.s.: non-significant, ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001.

    Eur J Cancer 2014 50(15), 2725-34. Rucaparib (AG-014699,PF-01367338) phosphate purchased from Selleck.

    Total cell extracts of BT-474 cells treated with increasing concentrations of olaparib or rucaparib were subjected to western blot analysis for PARP-1 and poly ADP-ribose (PAR) expression. β-tubulin was used as loading control. Representative images from two separate experiments are shown.

    Eur J Cancer 2014 50(15), 2725-34. Rucaparib (AG-014699,PF-01367338) phosphate purchased from Selleck.

  • purified PARP-1 and His-XPA were incubated alone ( lane 7 ), with activated PARP-1 (addition of activated DNA and NAD+, lane 8 ), or in the presence of the PARP inhibitor AG-014699 (lane 9 ). Following the various treatments, His-XPA was pulled down ( IP ) from each sample using cobalt-conjugated magnetic beads.

    J Biol Chem 2012 287, 39824-33. Rucaparib (AG-014699,PF-01367338) phosphate purchased from Selleck.

    Three sensitive and three resistant cell lines were treated for 24 h with 0.02% DMSO (negative control) or 10 uM rucaparib. Serving as positive control were cells fixed 30 min after exposure to 2 Gy IR. Image acquisition was performed with a confocal microscope (Leica TCS SP2) using the 100X objective and a 2X optical zoom and oil immersion. Red: γH2AX foci. Green: RAD51 foci. *P < 0.05 **P < 0.01 ***P < 0.001. Fluorescence microscopy images of DAPI-stained rucaparib-sensitive (HN4) and rucaparib-resistant (SAS) HNC cell lines treated with DMSO, 2 Gy or 10 uM rucaparib for 24 h.

    Oral Oncol 2014 50(9), 825-31. Rucaparib (AG-014699,PF-01367338) phosphate purchased from Selleck.

  • Antitumor effects of transfecting of INPP4B gene combined with PARP inhibitor treatment on PC3 cells. (A) The change of cell number and shape under the microscope. (B) The viability of PC3 cells measured using CCK-8. (C) The cell cycle phase distribution of PC3 detected by flow cytometry. (D) Apoptosis of PC3 cells detected using annexin V-FITC/PI staining. (Asterisks denote statistical significance between Lenti-INPP4B+PARP inhibitor and Lenti-INPP4B and PARP inhibitor treatment, *P<0.05).

    Urol Oncol 2014 32(5), 720-6. Rucaparib (AG-014699,PF-01367338) phosphate purchased from Selleck.

    in vivo suppression of PAR formation by the PARP inhibitor AG-014699 upon induction of DNA damage

    Primary human lung fibroblast cells (MRC-5) were pre-treated with the indicated concentration of the PARP inhibitor AG-014699 for two hours. Oxidative DNA damage was induced by 500 µM H2O2 for 10 min and cellular PARP activity was measured by immuno-staining of poly(ADP)-ribose (PAR) (right panels). The in vivo effect of PARP inhibition was compared to cells without DNA damage induction and inhibitor (control) and H2O2-treated cells without inhibitor.
    Average nuclear PAR staining intensities of more than 50 cells were statistically analysed by Kruskal-Wallis and the post-hoc Dunn’s Multiple Comparison tests (left panel). Asterisks indicate highly significant (p<1%) differences to H2O2-treated cells without PARP inhibitor. Thick horizontal bars mark medians and error bars the interquartile range.


    Dr. David Schrmann from University of Base. Rucaparib (AG-014699,PF-01367338) phosphate purchased from Selleck.




製品説明 Rucaparib (AG-014699, PF-01367338)は一種のPARP阻害剤で、無細胞試験でPARP1に作用する時のKi値が1.4 nMになって、残り8つPARPドメインにも結合親和力を表します。臨床3期。
特性 The first PARP inhibitor used in clinical trials combined with temozolomide.
PARP [1]
(Cell-free assay)
1.4 nM(Ki)

Rucaparib is a potent inhibitor of purified full-length human PARP-1 and shows higher inhibition of cellular PARP in LoVo and SW620 cells. Besides, Rucaparib binds detectably to eight other PARP domains, including PARP2, 3, 4, 10, 15, 16, TNKS1 and TNKS2. [1] [2] The radio-sensitization by Rucaparib is due to downstream inhibition of activation of NF-κB, and is independent of SSB repair inhibition. Rucaparib could target NF-κB activated by DNA damage and overcome toxicity observed with classical NF-κB inhibitors without compromising other vital inflammatory functions. [3] Rucaparib inhibits PARP-1 activity by 97.1% at a concentration of 1 μM in permeabilised D283Med cells. [4]

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
BT-474 NUPsWoNkTnWwY4Tpc44hSXO|YYm= Mn\MNE4yNzFxNUCwM|ExODBibl2= MmD1bY5pcWKrdIOgVGFTWCCjY4Tpeol1gSCjdDDzeIFzfGmwZzDjc45k\XKwdILheIlwdiCxZjC1NFAhdk1? M{\YeVI2OTJ6NEW1
BT474 M1Tpe2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUO1NFAhdk1? NHHSZnIyOOLCk{G1xsBl NHG0VFVz\WS3Y3XzJINmdGxiZ4Lve5RpKGmwIITo[UBnd3W{IHzpcoV{KGGwZDDzbYdvcW[rY3HueIx6 NWLs[nUyOjVzMki0OVU>
SKBR3 NH\x[IxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NY\FRWtqPTByIH7N MnnhNVDjiJNzNdMg[C=> NWS5cWlvemWmdXPld{Bk\WyuIHfyc5d1cCCrbjD0bIUh\m:3cjDsbY5meyCjbnSgd4lodmmoaXPhcpRtgQ>? MYqyOVEzQDR3NR?=
AU565 M{DXTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3jISVUxOCCwTR?= NEPDeYsyOOLCk{G1xsBl MnTHdoVlfWOnczDj[YxtKGe{b4f0bEBqdiC2aHWg[o92eiCuaX7ld{BidmRic3nncolncWOjboTsfS=> NIWxNYwzPTF{OES1OS=>
EFM192A NGHUfnpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Ml7UOVAxKG6P MkPxNVDjiJNzNdMg[C=> M1HPUpJm\HWlZYOgZ4VtdCCpcn;3eIghcW5idHjlJIZwfXJibHnu[ZMh[W6mIIPp[45q\mmlYX70cJk> M3TmV|I2OTJ6NEW1
MDA-MB-231 MXPGeY5kfGmxbjDBd5NigQ>? Mo\PNVAwOjBxNECg{txO NWjNXXY{OjRiaB?= NUDFTY1EcW6lcnXhd4V{KHBvQVvUJIxmfmWuczDpckBiKGSxc3Wt[IVx\W6mZX70JI1idm6nch?= NW\5T5VsOjR2MkCxOVI>
MDA-MB-231 NWW4RndXS2WubDDWbYFjcWyrdImgRZN{[Xl? NGq2bJgxNjFvNECg{txO MmjzNlQhcA>? M1;kN2lEPTEkgJm95qCKOTdwN{hCpO69VQ>? NYLMO4UyOjR2MkCxOVI>
MDA-MB-231 NFi4ZodCeG:ydH;zbZMhSXO|YYm= M2HlXVExNzJyL{SwJO69VQ>? M33vVVI1KGh? MWTpcoR2[2W|IHHwc5B1d3OrczDkc5NmKGSncHXu[IVvfGy7 MmjzNlQ1OjBzNUK=
MDA-MB-231 NF\DdZhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVWxNE8zOC92MDFOwG0> MoTNNlQhcA>? NIjKXGdjdG:la4OgZ4VtdCCleXPs[UBxem:pcnXzd4lwdiCrbjDHNk9OKHCqYYPl Mmn5NlQ1OjBzNUK=
H460 NFnk[ZhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVH0dlV4PDByIH7N M4\RUlI1yqCq MX\pcoNz\WG|ZYOgZ4VtdHWuYYKgdoFlcW:|ZX7zbZRqfmm2eR?= MYiyOFQyOTZzMR?=
A549  MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWH1SWtLPDByIH7N NUjyenpqOjUEoHi= M2XE[Ylv[3KnYYPld{Bk\WyudXzhdkBz[WSrb4PlcpNqfGm4aYT5 MUSyOFQyOTZzMR?=
DT40 NWKwNIhCT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3L6UGlEPTB;MkGgcm0> NGjj[ZQzPDN3NkixNy=>
DU145 MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVfJR|UxRTF6IH7N MVGyOFM2PjhzMx?=
COLO704 M4nhc2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NW\iRmpPUUN3ME2yMlUzKMLzIECuOlch|ryP MYSyN|czQTRyMh?=
OVMANAb Mmf1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoT1TWM2OD1{LkW4JOKyKDBwM{ig{txO NGXsUFUzOzd{OUSwNi=>
OV177 NHvMVoxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MU\JR|UxRTJwN{igxtEhOC55MTFOwG0> NUjMUXpROjN5Mkm0NFI>
OAW28 M3\McGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M376WGlEPTB;Mz62NUDDuSByLkK4JO69VQ>? M3HOVlI{PzJ7NECy
OVSAHO Mn;IS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHfHW5pKSzVyPUOuOlQhyrFiMD6zN{DPxE1? NUDGd3kxOjN5Mkm0NFI>
OVKATE MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MY\JR|UxRTNwNkSgxtEhOS55OTFOwG0> M2\1R|I{PzJ7NECy
OVCAR3 M2jVZ2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEHJPYRKSzVyPUOuO|QhyrFiMD60NEDPxE1? NVnzd4ZCOjN5Mkm0NFI>
PEO14 MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXnaeHh7UUN3ME2zMlg1KMLzIECuO|Yh|ryP MXmyN|czQTRyMh?=
A2780 NUH3d|ZTT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NE\BRYlKSzVyPUOuPVQhyrFiMD6yOUDPxE1? NWC1bIRwOjN5Mkm0NFI>
KURAMOCHIb Mk\rS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEiyXGVKSzVyPUSuN|QhyrFiMD6yPUDPxE1? MXmyN|czQTRyMh?=
TOV21G M{DxRmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGHpW4NKSzVyPUWuNFchyrFiMT6zNEDPxE1? M4DvVlI{PzJ7NECy
OVISE NXnCTpFvT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1y4c2lEPTB;NT62PEDDuSByLkKzJO69VQ>? NV\meY5EOjN5Mkm0NFI>
KK NVzBcFJtT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1mxbmlEPTB;Nj6xOUDDuSBzLkSyJO69VQ>? MX2yN|czQTRyMh?=
PEO6 MXfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmPGTWM2OD15LkC2JOKyKDBwN{Sg{txO NEL2eZEzOzd{OUSwNi=>
OVCA429 NXqxfmQ3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWT6T3R7UUN3ME24MlI6KMLzIEGuOlQh|ryP NF7iSXozOzd{OUSwNi=>
OV167 MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUHIZVY4UUN3ME24MlM{KMLzIEGuNVgh|ryP MYWyN|czQTRyMh?=
RMG1 MljkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVnHepY4UUN3ME25MlMzKMLzIEKuN|Yh|ryP NEnwfokzOzd{OUSwNi=>
OVCAR5 MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Ml7WTWM2OD17LkWwJOKyKDJwNUmg{txO NFHxV40zOzd{OUSwNi=>
EFO21 MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYfJR|UxRTlwOUKgxtEhOS56NzFOwG0> M4nsT|I{PzJ7NECy
ES2 MlHtS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVTJNWdIUUN3ME2xNE4yOiEEsTCxMlI{KM7:TR?= MmX1NlM4Ojl2MEK=
Tyk-nu MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{DT[GlEPTB;MUCuNlAhyrFiMT6xNkDPxE1? MnPmNlM4Ojl2MEK=
CAOV3 NVfmc5c2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M33MUGlEPTB;MUCuN|chyrFiMD64O{DPxE1? NWq4eYhJOjN5Mkm0NFI>
OV207 MWXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1SyOGlEPTB;MUKuNlchyrFiMD6zNkDPxE1? MYGyN|czQTRyMh?=
HEY MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4nlN2lEPTB;MUOuNFEhyrFiMD63OUDPxE1? NV20UVRXOjN5Mkm0NFI>
DOV13 M{mzN2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnH3TWM2OD5zNTFOwG0> MlLpNlM4Ojl2MEK=
EFO27 NFTN[lZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUPncG57UUN3ME6xOUDPxE1? M1zyWlI{PzJ7NECy
HEY C2 M4LTc2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MV7JR|UxRjF3IN88US=> M1zCWVI{PzJ7NECy
KOC-7cc M{KzWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXLGW5VVUUN3ME6xOUDPxE1? NWnIUmtpOjN5Mkm0NFI>
MCASb M3jBUGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUfJR|UxRjF3IN88US=> MXqyN|czQTRyMh?=
OAW42 NXuxWHAzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1PqZWlEPTB-MUWg{txO MYWyN|czQTRyMh?=
OV2008 Mnf4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mk\zTWM2OD5zNTFOwG0> NIrRW5MzOzd{OUSwNi=>
OV90 MkfTS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmKxTWM2OD5zNTFOwG0> M2rUNlI{PzJ7NECy
OVCA420b MnLFS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MV\JR|UxRjF3IN88US=> NFHxdoczOzd{OUSwNi=>
OVCA432 NVHoWGYzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHq2XlNKSzVyPkG1JO69VQ>? MUOyN|czQTRyMh?=
PEA2 MX3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFHhSWpKSzVyPkG1JO69VQ>? NVzJO2FWOjN5Mkm0NFI>
SKOV3 NYnTOm1{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlrVTWM2OD5zNTFOwG0> NUnrXolxOjN5Mkm0NFI>
TOV112D M{LU[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mn32NE0{KM7:TR?= Mmr6TWM2OD5zNTFOwG0> MUmyN|czQTRyMh?=
C4-2 NIi2S2FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHO4RnIxNTNizszN NUnR[GRROTRiZB?= NHjYVVFFVVOR Ml[5[IVkemWjc3XzJINwdG:weTDueY1j\XJiZH;z[UBl\XCnbnTlcpRtgQ>? MlzsNlM2PjV{NES=
PC3 NFGwb5BIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mn3qNE0{KM7:TR?= NGjIbVQyPCCm NWjhNnBETE2VTx?= MX7k[YNz\WG|ZYOgZ49td267IH71cYJmeiCmb4PlJIRmeGWwZHXueIx6 NGrN[VAzOzV4NUK0OC=>
DU145 MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnHlNE0{KM7:TR?= MVexOEBl NF3OTlFFVVOR NWLMXYR7\GWlcnXhd4V{KGOxbH;ufUBvfW2kZYKg[I9{\SCmZYDlcoRmdnSueR?= MkTtNlM2PjV{NES=
VCaP  MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGTncmoxNTNizszN MlvoNVQh\A>? NFfzSVFFVVOR M37zdIRm[3KnYYPld{Bkd2yxbomgcpVu[mW{IHTvd4Uh\GWyZX7k[Y51dHl? MYeyN|U3PTJ2NB?=
LNCaP  NWe5R25kT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWDlOnZrOC1|IN88US=> MUCxOEBl MYLEUXNQ M1PIZ4Rm[3KnYYPld{Bkd2yxbomgcpVu[mW{IHTvd4Uh\GWyZX7k[Y51dHl? M2PhTFI{PTZ3MkS0


体内試験 Rucaparib is not toxic but significantly enhances temozolomide-induced TGD in the DNA repair protein-competent D384Med xenografts. Pharmacokinetics studies also show that Rucaparib is detected in the brain tissue, which indicates that Rucaparib has potential in intra-cranial malignancy therapy. [4] Rucaparib significantly potentiates the cytotoxicity of topotecan and temozolomide in NB-1691, SH-SY-5Y, and SKNBE (2c) cells. Rucaparib enhances the antitumor activity of temozolomide and indicates complete and sustained tumor regression in NB1691 and SHSY5Y xenografts. [5]


+ 展開

Ki Determination:

Inhibition of human full-length recombinant PARP-1 by [32P]NAD+ incorporation is measured. The [32P]ADP-ribose incorporated into acid insoluble material is quantified using a PhosphorImager. Ki is calculated by nonlinear regression analysis.
細胞試験: [4]
+ 展開
  • 細胞株: D425Med, D283Med and D384Med cells
  • 濃度: 0.4 μM
  • 反応時間: 3 or 5 days
  • 実験の流れ: Medulloblastoma cell lines are seeded in 96-well plates at a density of 1 × 103, 3 × 103 and 3 × 103, respectively. At 24 hours (D384Med) or 48 hours (D283Med and D425Med) after seeding, the cells are exposed to various concentrations of temozolomide in the presence or absence of 0.4 μM Rucaparib. After 3 days (D425Med and D384Med) or 5 days (D283Med) of culture, cell viability is evaluated by a XTT cell proliferation kit assay. Cell growth is expressed as a percentage in relation to DMSO or 0.4 μM Rucaparib-alone controls. The concentration of temozolomide, alone or in combination with Rucaparib that inhibited growth by 50% (GI50) is calculated. The potentiation factor 50 (PF50) is defined as the ratio of the GI50 of temozolomide in the presence of Rucaparib to the GI50 of temozolomide alone.
+ 展開
  • 動物モデル: CD-1 nude mice bearing established D283Med xenografts
  • 製剤: Normal saline
  • 投薬量: 1 mg/kg
  • 投与方法: One or four daily by i.p.

溶解度 (25°C)

体外 DMSO 84 mg/mL (199.35 mM)
Water slightly soluble or insoluble
Ethanol slightly soluble or insoluble
体内 順序で溶剤を入れること:
30% propylene glycol, 5% Tween 80, 65% D5W
30 mg/mL

* 溶解度検測はSelleck技術部門によって行いますので、文献より提供された溶解度と差異がある可能性がありますが、生産工芸と不同ロット(lot)で起きる正常な現象ですから、ご安心ください。


分子量 421.36


CAS No. 459868-92-9
in solvent
別名 N/A





マス (g) = 濃度 (mol/L) x ボリューム (L) x 分子量 (g/mol)


  • マス




貯蔵液を準備することを要求される希釈剤を計算してください. セレック希釈計算器は、以下の方程式に基づきます:

開始濃度 x 開始体積 = 最終濃度 x 最終体積


この方程式は、一般に略語を使われます:C1V1 = C2V2 ( 輸入 輸出 )

  • C1



  • 連続希釈剤

  • 計算結果

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):




チップス: 化学式は大文字と小文字の区別ができます。C10H16N2O2 c10h16n2o2


マス 濃度 ボリューム 分子量


NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02975934 Recruiting Metastatic Castration Resistant Prostate Cancer Clovis Oncology, Inc.|Foundation Medicine January 2017 Phase 3
NCT02986100 Recruiting Solid Tumor Clovis Oncology, Inc. November 2016 Phase 1
NCT02952534 Recruiting Metastatic Castration Resistant Prostate Cancer Clovis Oncology, Inc.|Foundation Medicine November 2016 Phase 2
NCT02855944 Recruiting Ovarian Cancer|Epithelial Ovarian Cancer|Fallopian Tube Cancer|Peritoneal Cancer Clovis Oncology, Inc.|Foundation Medicine September 2016 Phase 3
NCT02740712 Recruiting Neoplasms Clovis Oncology, Inc. March 2016 Phase 1
NCT02505048 Recruiting Metastatic Breast Cancer UNICANCER|Clovis Oncology, Inc.|Fondation ARC March 2016 Phase 2



Handling Instructions


  • * 必須


PARP Inhibitors with Unique Features


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細胞株 試験類型 濃度 培養時間 溶剤類型 活性叙述 PMID