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Picropodophyllin (PPP)

別名: AXL1717 中文名稱：苦鬼臼毒素

Picropodophyllin (PPP, AXL1717)是一種選擇性IGF-1R抑制劑，IC50為1 nM。它對(duì)IGF-IR具有高選擇性，對(duì)IR的酪氨酸磷酸化或FGF-R、PDGF-R、EGF-R沒(méi)有抑制作用。Picropodophyllin (PPP)可誘導(dǎo)凋亡并具有抗腫瘤活性。

Picropodophyllin (PPP) Chemical Structure

Picropodophyllin (PPP) Chemical Structure

CAS: 477-47-4

規(guī)格 價(jià)格 庫(kù)存 購(gòu)買數(shù)量
10mM (1mL in DMSO) 1040.13 現(xiàn)貨
5mg 810.01 現(xiàn)貨
25mg 2422.47 現(xiàn)貨
100mg 5701.86 現(xiàn)貨
1g 24324.3 現(xiàn)貨
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Picropodophyllin (PPP)相關(guān)產(chǎn)品

相關(guān)信號(hào)通路圖

IGF-1R Signaling Pathways

IGF-1R信號(hào)通路圖

細(xì)胞實(shí)驗(yàn)數(shù)據(jù)示例

細(xì)胞系 實(shí)驗(yàn)類型 給藥濃度 孵育時(shí)間 活性描述 文獻(xiàn)信息
P-388 neoplastic cell line Cytotoxic?assay In vitro cytotoxicity against the P-388 (from DBA/2 mouse) neoplastic cell line, IC50=60 nM 14980682
A-549 (human lung carcinoma) neoplastic cell line Cytotoxic?assay In vitro cytotoxicity against the A-549 (human lung carcinoma) neoplastic cell line, IC50=60 nM 14980682
HT-29 (human colon carcinoma) neoplastic cell line Cytotoxic?assay In vitro cytotoxicity against the HT-29 (human colon carcinoma) neoplastic cell line, IC50=60 nM 14980682
amnion cells Antiviral assay Antiviral activity against HSV1 infected in human primary amnion cells assessed as inhibition of virus-induced pathogenic effect, Activity = 1.9 μM. 9834179
P388 Cytotoxicity assay Cytotoxicity against mouse P388 cells, IC50 = 6 μM. 7673931
A549 Cytotoxicity assay Cytotoxicity against human A549 cells, IC50 = 6 μM. 7673931
HT-29 Cytotoxicity assay Cytotoxicity against human HT-29 cells, IC50 = 6 μM. 7673931
TC32 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells 29435139
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells 29435139
SJ-GBM2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells 29435139
NB-EBc1 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells 29435139
Saos-2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells 29435139
LAN-5 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells 29435139
BT-12 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells 29435139
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells) 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-MC cells 29435139
BT-12 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-12 cells 29435139
LAN-5 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for LAN-5 cells 29435139
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for DAOY cells 29435139
NB-EBc1 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB-EBc1 cells 29435139
BT-37 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-37 cells 29435139
TC32 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells 29435139
MG 63 (6-TG R) qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for MG 63 (6-TG R) cells 29435139
U-2 OS qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for U-2 OS cells 29435139
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for RD cells 29435139
Saos-2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Saos-2 cells 29435139
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生物活性

產(chǎn)品描述 Picropodophyllin (PPP, AXL1717)是一種選擇性IGF-1R抑制劑，IC50為1 nM。它對(duì)IGF-IR具有高選擇性，對(duì)IR的酪氨酸磷酸化或FGF-R、PDGF-R、EGF-R沒(méi)有抑制作用。Picropodophyllin (PPP)可誘導(dǎo)凋亡并具有抗腫瘤活性。
靶點(diǎn)
IGF-1R [1]
(Cell-free assay)
1 nM
體外研究(In Vitro)
體外研究活性

在完整細(xì)胞中，PPP有效抑制IGF-1刺激的IGF-1R，Akt (Ser 473)和 Erk1/2磷酸化。在培養(yǎng)的IGF-1R 陽(yáng)性腫瘤細(xì)胞中，Picropodophyllin特異性抑制細(xì)胞生長(zhǎng)，并誘導(dǎo)細(xì)胞凋亡。[1] Picropodophyllin通過(guò)進(jìn)一步降低細(xì)胞活性并增強(qiáng)細(xì)胞凋亡，協(xié)同使HMCL，原代人MM 和小鼠5T33MM細(xì)胞對(duì)ABT-737 和 ABT-199更敏感。[3] Picropodophyllin 協(xié)同抑制肝細(xì)胞癌的增殖和活性。[4]
激酶實(shí)驗(yàn) 體外酪氨酸激酶試驗(yàn)。
IGF-1R催化的pTG底物磷酸化測(cè)定使用96孔板酪氨酸激酶試劑盒進(jìn)行。我們使用重組表皮生長(zhǎng)因子受體，HEPG2免疫沉淀物IR，P6細(xì)胞免疫沉淀物IGF-1R，以及來(lái)自P6 (代表“非-IGF-1R 酪氨酸激酶”)的IGF-1R免疫沉淀上清液。用所需化合物將受體在激酶緩沖液[50 mM HEPES 緩沖液(pH 7.4)，20 mM MgCl2，0.1 MnCl2，和0.2 Na3VO4]中處理30分鐘，激酶反應(yīng)通過(guò)加入ATP激活。磷酸化聚合體底物用與辣根過(guò)氧化物酶共軛的磷酸酪氨酸特異性單克隆抗體，克隆PT-66探測(cè)。通過(guò)辣根過(guò)氧化物酶底物鄰苯二胺二鹽酸化物顯色，并通過(guò)分光光度法(ELISA 閱讀器)定量。IGF-1R酪氨酸自磷酸化通過(guò)夾心ELISA法進(jìn)行分析。簡(jiǎn)而言之，96孔板用1微克/孔的IGF-1R β亞型抗體涂覆，在4℃下培養(yǎng)過(guò)夜。板用1% BSA在PBS Tween中封存1小時(shí)，然后將來(lái)自P6細(xì)胞系的總蛋白裂解物以80微克/孔加入。使用來(lái)自R細(xì)胞系的總蛋白裂解物作為陰性對(duì)照。將研究的化合物加入不含ATP的酪氨酸激酶緩沖液，在室溫下進(jìn)行30分鐘，再用ATP活化激酶。激酶測(cè)定使用Sigma 試劑盒(如上)進(jìn)行。分光光度法后，使用軟件程序的REGRESSION函數(shù)測(cè)定抑制劑的IC50值。
細(xì)胞實(shí)驗(yàn) 細(xì)胞系 黑色素瘤細(xì)胞(FM 55，SK-MEL-28，SK-MEL-5，C8161，DFB，DFW 和 AA)，肉瘤細(xì)胞(RD-ES)，乳腺癌細(xì)胞(MCF 7)，前列腺癌細(xì)胞(PC3)，肝癌細(xì)胞(HepG2)和胚胎小鼠成纖維細(xì)胞(P6 和 R-)
濃度 ~15 μM
孵育時(shí)間 48小時(shí)
方法

測(cè)定使用細(xì)胞增殖試劑盒II，基于黃色四唑鎓鹽2,3-雙[2-甲氧基-4-硝基-5-磺苯基] -2H-四唑鎓-5-羧酰苯胺內(nèi)鹽在橙色甲瓚染料中被活細(xì)胞呼吸鏈改變色度的原理進(jìn)行。所有參照標(biāo)準(zhǔn)和實(shí)驗(yàn)以一式三份進(jìn)行。
實(shí)驗(yàn)圖片 檢測(cè)方法 檢測(cè)指標(biāo) 實(shí)驗(yàn)圖片 PMID
Western blot p-IGFR1 / p-AKT / p-ERK 22363814
Growth inhibition assay Cell viability 22159423
體內(nèi)研究(In Vivo)
體內(nèi)研究活性

在異種移植人ES-1，BE，和PC3的SCID小鼠體內(nèi)，Picropodophyllin (20 mg/kg/12 h, i.p.)引起完全的腫瘤退化。[1]在5T33MM小鼠模型中，Picropodophyllin也表現(xiàn)出有效的抗腫瘤活性，并使存活率顯著增加。[2]
動(dòng)物實(shí)驗(yàn) Animal Models 負(fù)荷表達(dá)IGF-1R，或 R- v-src (IGF-1R 陰性) 和 P12 (過(guò)表達(dá) IGF-1 和 IGF-1R)的 ES-1，BE，或 PC3 異種移植物的SCID小鼠
Dosages 20 mg/kg/12 h
Administration i.p.
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT06357884 Recruiting
Diabetic Neuropathies|Plantar Callus
Chinese University of Hong Kong|Princess Margaret Hospital Hong Kong
 February 23 2024 Not Applicable
NCT05710185 Recruiting
Palmoplantar Pustulosis
Brigham and Women''s Hospital|University of Pennsylvania
 July 1 2023 Phase 4
NCT06025422 Recruiting
Diabetic Foot Ulcer|Diabetic Neuropathies
University Hospitals Leicester|University of Salford
 March 13 2023 --
NCT04433052 Recruiting
Coronary Heart Disease
Tampere University
 February 1 2023 Not Applicable
NCT05740137 Active not recruiting
Colorectal Cancer|Colorectal Adenoma|Colorectal Neoplasms
Ismail G?genur|Nyk?bing Falster County Hospital|Naestved Hospital|Holbaek Sygehus|Slagelse Hospital|Zealand University Hospital
 October 1 2022 Not Applicable

化學(xué)信息&溶解度

分子量 414.41 分子式

C22H22O8
CAS號(hào) 477-47-4 SDF Download Picropodophyllin (PPP) SDF
Smiles COC1=CC(=CC(=C1OC)OC)C2C3C(COC3=O)C(C4=CC5=C(C=C24)OCO5)O
儲(chǔ)存條件(自收到貨起)

體外溶解度
批次：

DMSO : 83 mg/mL ( (200.28 mM) ；DMSO吸濕會(huì)降低化合物溶解度，請(qǐng)使用新開(kāi)封DMSO)

Ethanol : 1.5 mg/mL (3.61 mM)

Water : Insoluble

摩爾濃度計(jì)算器

體內(nèi)溶解度
批次：

現(xiàn)配現(xiàn)用，請(qǐng)按從左到右的順序依次添加，澄清后再加入下一溶劑

 動(dòng)物體內(nèi)配方計(jì)算器

實(shí)驗(yàn)計(jì)算

摩爾濃度計(jì)算器

質(zhì)量 濃度 體積 分子量

動(dòng)物體內(nèi)配方計(jì)算器（澄清溶液）

第一步：請(qǐng)輸入基本實(shí)驗(yàn)信息（考慮到實(shí)驗(yàn)過(guò)程中的損耗，建議多配一只動(dòng)物的藥量）

mg/kg g μL 只

第二步：請(qǐng)輸入動(dòng)物體內(nèi)配方組成（配方適用于不溶于水的藥物；不同批次藥物配方比例不同，請(qǐng)聯(lián)系Selleck為您提供正確的澄清溶液配方）

% DMSO % % Tween 80 % ddH2O
%DMSO %

計(jì)算結(jié)果：

工作液濃度： mg/ml；

DMSO母液配制方法： mg 藥物溶于μL DMSO溶液（母液濃度mg/mL，注：如該濃度超過(guò)該批次藥物DMSO溶解度，請(qǐng)先聯(lián)系Selleck）；

體內(nèi)配方配制方法：取μL DMSO母液，加入μL PEG300，混勻澄清后加入μL Tween 80，混勻澄清后加入μL ddH2O，混勻澄清。

體內(nèi)配方配制方法：取μL DMSO母液，加入μL Corn oil，混勻澄清。

注意：1. 首先保證母液是澄清的；
2.一定要按照順序依次將溶劑加入，進(jìn)行下一步操作之前必須保證上一步操作得到的是澄清的溶液，可采用渦旋、超聲或水浴加熱等物理方法助溶。

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常見(jiàn)問(wèn)題及建議解決方法

問(wèn)題 1:
I am currently setting the conditions for in vivo experiments, how should I reconstitute the drug?

回答：
Other than DMSO:vegetable oil 10:1 (v/v) cited from reference. We tested another formulation: 4% DMSO+corn oil. S7668 Picropodophyllin (PPP) can be dissolved in it at 5 mg/ml clearly. But after stayed for about 20-30 min, the two phase would separate and wouldn't get together again. So if you are going to use this formulation, please prepare the fresh solution just before use.

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