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Daporinad (FK866)

別名: APO866 中文名稱：達珀利奈

Daporinad (FK866)有效抑制煙酰胺磷酸核糖轉(zhuǎn)移酶(NMPRTase; Nampt)，Daporinad (FK866) 可引發(fā)自噬，無細胞試驗中IC50為0.09 nM。Phase 1/2。

Daporinad (FK866) Chemical Structure

Daporinad (FK866) Chemical Structure

CAS: 658084-64-1

規(guī)格 價格 庫存 購買數(shù)量
10mM (1mL in DMSO) 1613.43 現(xiàn)貨
5mg 737.65 現(xiàn)貨
10mg 1405.61 現(xiàn)貨
25mg 3025.95 現(xiàn)貨
50mg 4662.84 現(xiàn)貨
1g 24488.1 現(xiàn)貨
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常與Daporinad (FK866)一起在實驗中被使用的化合物

Olaparib (AZD2281)

Daporinad和Olaparib誘導(dǎo)雙鏈DNA斷裂并促進OV1946or細胞凋亡。

Sauriol A, et al. Sci Rep. 2023 Feb 27;13(1):3334.

Niraparib (MK-4827)

Daporinad和Niraparib抑制olaparib耐藥細胞系OV1946的細胞生長。

Sauriol A, et al. Sci Rep. 2023 Feb 27;13(1):3334.

KPT 9274 (ATG-019)

Daporinad和KPT9274是NMPT抑制劑，可以強烈降低M2巨噬細胞中的總NAD+水平和線粒體呼吸。

Weinhauser I, et al. Sci Adv. 2023 Apr 14;9(15):eadf8522.

GMX1778

Daporinad和GMX1778是iNAMPT酶抑制劑，已被開發(fā)為抗癌治療選擇。

Sun BL, et al. EBioMedicine. 2020 Nov;61:103059.

Carboplatin

Daporinad和Carboplatin聯(lián)合使用在抑制卵巢癌耐藥細胞增殖方面具有更好的效果。

Park M, et al. Front Biosci (Landmark Ed). 2023 Mar 10;28(3):47.

Daporinad (FK866)相關(guān)產(chǎn)品

相關(guān)信號通路圖

Transferase Signaling Pathways

Transferase信號通路圖

細胞實驗數(shù)據(jù)示例

細胞系 實驗類型 給藥濃度 孵育時間 活性描述 文獻信息
MCF7 Antitumor assay 10 uM 6 days Antitumor activity against human MCF7 cells at 10 uM after 6 days by SRB assay, IC50 = 0.68 μM. 21330015
MDCK Function assay 10 uM Apparent permeability across apical to basolateral side in dog MDCK cells at 10 uM by LC-MS/MS analysis 23859118
NYH Cytotoxicity assay 3 weeks Cytotoxicity against human NYH cells after 3 weeks by clonogenic survival assay, LD50 = 0.0015 μM. 23679915
A2780 Cytotoxicity assay 72 hrs Cytotoxicity against human A2780 cells after 72 hrs by SRB assay, IC50 = 0.001 μM. 23617784
K562 Cytotoxicity assay 6 days Cytotoxicity against human K562 cells after 6 days by SRB assay, IC50 = 20 μM. 21330015
SNU638 Cytotoxicity assay 6 days Cytotoxicity against human SNU638 cells after 6 days by SRB assay, IC50 = 0.16 μM. 21330015
HCT116 Cytotoxicity assay 6 days Cytotoxicity against human HCT116 cells after 6 days by SRB assay, IC50 = 0.16 μM. 21330015
A549 Cytotoxicity assay 6 days Cytotoxicity against human A549 cells after 6 days by SRB assay, IC50 = 0.16 μM. 21330015
HT1080 Cytotoxicity assay 6 days Cytotoxicity against human HT1080 cells after 6 days by SRB assay, IC50 = 0.16 μM. 21330015
SH-SY5Y Cytotoxicity assay 48 hrs Cytotoxicity against human SH-SY5Y cells assessed as cell viability after 48 hrs by MTT assay, IC50 = 0.0017 μM. 19961183
K562 Cytotoxicity assay 96 hrs Cytotoxicity against human K562 cells after 96 hrs by MTT assay, IC50 = 0.0072 μM. 23679915
A2780 Antiproliferative assay 72 hrs Antiproliferative activity against human A2780 cells assessed as growth inhibition after 72 hrs by SRB-based microplate reader analysis, IC50 = 0.001 μM. 23859118
A2780 Cytotoxicity assay 72 hrs Cytotoxicity against human A2780 cells assessed as growth inhibition after 72 hrs by WST-1 assay, IC50 = 0.0016 μM. 24164086
HepG2 Function assay 1 hr Inhibition of NAMPT in human HepG2 cells using [14C]-nicotinamide/PRPP as substrate assessed as formation of [14C]-nicotinamide mononucleotide after 1 hr by liquid scintillation counting analysis, IC50 = 0.0022 μM. 24164086
MCF-7 Cytotoxicity assay 72 hrs Cytotoxicity against human MCF-7 cells assessed as growth inhibition after 72 hrs by WST-1 assay, IC50 = 0.0074 μM. 24164086
HCT116 Cytotoxicity assay 72 hrs Cytotoxicity against human HCT116 cells assessed as growth inhibition after 72 hrs by WST-1 assay, IC50 = 0.0109 μM. 24164086
HCT116 Cytotoxicity assay 72 hrs Cytotoxicity against APO866-resistant human HCT116 cells assessed as growth inhibition after 72 hrs by WST-1 assay, IC50 = 0.946 μM. 24164086
A2780 Antiproliferative assay 72 hrs Antiproliferative activity against human A2780 cells after 72 hrs by sulforhodamine B assay, IC50 = 0.001 μM. 24405419
A2780 Function assay 72 hrs Inhibition of NAMPT in human A2780 cells assessed as decrease in cell viability after 72 hrs by SRB assay, IC50 = 0.001 μM. 27541271
DE3 Function assay 15 mins Inhibition of human full length C-terminal His6-tagged NAMPT expressed in Escherichia coli Rosetta (DE3) cells using nicotinamide as substrate incubated for 15 mins prior to substrate addition measured after 30 mins in presence of PRPP, IC50 = 0.003 μM. 27541271
SH-SY5Y Cytotoxicity assay 56 hrs Cytotoxicity against human SH-SY5Y cells assessed as reduction in cell viability after 56 hrs by MTT assay, EC50 = 0.0034 μM. 28165742
PC3 Antiproliferative assay 5 days Antiproliferative activity against human PC3 cells assessed as reduction in cell viability incubated for 5 days by Cell-titer Glo reagent based assay, IC50 = 0.0057 μM. 28610984
HepG2 Cytotoxicity assay 72 hrs Cytotoxicity in human HepG2 cells assessed as reduction in cell viability after 72 hrs by MTT assay, IC50 = 0.89 μM. 28885834
MDA-MB-231 Cytotoxicity assay 72 hrs Cytotoxicity in human MDA-MB-231 cells assessed as reduction in cell viability after 72 hrs by MTT assay, IC50 = 1.3 μM. 28885834
HCT116 Cytotoxicity assay 72 hrs Cytotoxicity in human HCT116 cells assessed as reduction in cell viability after 72 hrs by MTT assay, IC50 = 1.6 μM. 28885834
HepG2 Cytotoxicity assay 72 hrs Cytotoxicity against human HepG2 cells assessed as inhibition of cell growth after 72 hrs by MTT assay, IC50 = 0.89 μM. 29348808
HCT116 Cytotoxicity assay 72 hrs Cytotoxicity against human HCT116 cells assessed as inhibition of cell growth after 72 hrs by MTT assay, IC50 = 1.6 μM. 29348808
A549 Cytotoxicity assay 72 hrs Cytotoxicity against human A549 cells assessed as inhibition of cell growth after 72 hrs by MTT assay, IC50 = 3.7 μM. 29348808
SH-SY5Y Autophagy assay 40 hrs Induction of autophagy in human SH-SY5Y cells assessed as LC3/phosphotidylethanolamine coupling after 40 hrs by Western blot analysis 19961183
MCF7 Antitumor assay 6 days Antitumor activity against human MCF7 cells after 6 days by SRB assay 21330015
MCF7 Cytotoxicity assay 96 hrs Cytotoxicity against human MCF7 cells after 96 hrs by clonogenic assay 24164086
A2780 Antiproliferative assay 72 hrs Antiproliferative activity against human A2780 cells after 72 hrs by sulforhodamine B assay in presence of nicotinamide mononucleotide 24405419
Sf9 Function assay 30 mins Inhibition of recombinant full length human C-terminal His/flag-tagged HDAC1 expressed in baculovirus infected Sf9 insect cells after 30 mins by fluorescence assay 29348808
SH-SY5Y Cytotoxicity assay Cytotoxicity against human SH-SY5Y cells assessed as reduction of total cellular NAD(P) level, IC50 = 0.0005 μM. 19961183
NYH Cytotoxicity assay Cytotoxicity against human NYH cells by clonogenic assay, IC50 = 0.0015 μM. 24164086
PC3 Cytotoxicity assay Cytotoxicity against human PC3 cells by clonogenic assay, IC50 = 0.0038 μM. 24164086
A2780 Cytotoxicity assay Cytotoxicity against human A2780 cells by clonogenic assay, IC50 = 0.0057 μM. 24164086
A431 Cytotoxicity assay Cytotoxicity against human A431 cells by clonogenic assay, IC50 = 0.0061 μM. 24164086
MCF7 Cytotoxicity assay Cytotoxicity against human MCF7 cells by clonogenic assay, IC50 = 0.0084 μM. 24164086
SKOV3 Cytotoxicity assay Cytotoxicity against human SKOV3 cells by clonogenic assay, IC50 = 0.211 μM. 24164086
A2780 Cytotoxicity assay Cytotoxicity against human A2780 cells assessed as reduction in cell viability, IC50 = 0.0042 μM. 28165742
DU145 Cytotoxicity assay Cytotoxicity against human DU145 cells by clonogenic assay 24164086
HCT116 Function assay Resistance factor, ratio of IC50 for APO866-resistant human HCT116 cells to IC50 for human HCT116 cells 24164086
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生物活性

產(chǎn)品描述 Daporinad (FK866)有效抑制煙酰胺磷酸核糖轉(zhuǎn)移酶(NMPRTase; Nampt)，Daporinad (FK866) 可引發(fā)自噬，無細胞試驗中IC50為0.09 nM。Phase 1/2。
靶點
NMPRTase [5]
(Cell-free assay)
0.4 nM(Ki)
體外研究(In Vitro)
體外研究活性 APO866在0.09-27 nM的低濃度范圍內(nèi)會在41血液惡性腫瘤細胞中誘導(dǎo)產(chǎn)生細胞毒性，包括急性髓細胞白血病[AML]，急性淋巴細胞白血病 [ALL], 套細胞淋巴瘤[MCL], 慢性淋巴細胞白血病[CLL]和 T細胞淋巴瘤，這種毒性具有劑量依賴特性. APO866在0-10 nM的低濃度范圍內(nèi)會誘導(dǎo)細胞死亡，這一效果與線粒體膜去極化有關(guān)而與半胱天冬酶的激活無關(guān)。APO866在0-10 nM的濃度范圍內(nèi)會誘導(dǎo)胞內(nèi)NAD 和 ATP 的損耗和多種血液腫瘤細胞的死亡，這一效果具有劑量依賴特性[1] 。10 nM APO866 會抑制HFFF2細胞內(nèi) PBEF誘導(dǎo)的 MMP-3, CCL2和CXCL8 的分泌 [2]。
細胞實驗 細胞系 41血液惡性腫瘤細胞系
濃度 0 - 10 nM
孵育時間 72 小時或 96小時
方法

MTT 分析流程, 細胞按每毫升0.5 &time 106 個的密度接種到96孔板，接種三份。將APO866 (0.01 nM-100 nM) 加到50 μL 培養(yǎng)基中, 空白培養(yǎng)基作為對照。 孵育 72或 96 小時后每孔加入15 μL 染料溶液繼續(xù)孵育 4 小時。 然后每孔加入100 μL 終止液孵育 1小時，用分光光度計測量570 nm 處吸光度。臺盼藍染色分析流程, 細胞按每孔0.5 &time105 個接種到6孔板，每孔加入1 mL培養(yǎng)基，在含有或缺少 APO866的情況下孵育 96 小時。 每孔取10μL 細胞樣品與10 μL 臺盼藍孵育1分鐘（體積比1:1）。細胞存活情況通過計算未染色的細胞個數(shù)來獲得。
實驗圖片 檢測方法 檢測指標 實驗圖片 PMID
Western blot SIRT1 p-AMPK / AMPK / p-EIF2A / EIF2A / p-4EBP1 / 4EBP1 AKT / pAKT(Ser-473) / mTOR / p-mTOR(Ser-2448) 29905535
Immunofluorescence pMLKL phGSK3β ph-β-catenin 29996103
Growth inhibition assay

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