PP121

카탈로그 번호S2622 배치:S262201

인쇄

기술 자료

화학식

C17H17N7
분자량 319.36 CAS 번호 1092788-83-4
용해도 (25°C)* 시험관 내(In vitro) DMSO 32 mg/mL (100.2 mM)
Water Insoluble
Ethanol Insoluble
생체 내(In Vivo) (개별적으로 순서대로 용매를 제품에 첨가하십시오.)
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution
5%DMSO Corn oil

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 2.500mg/ml (7.83mM) Taking the 1 mL working solution as an example, add 50 μL of 50 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml은 약간 용해되거나 불용해됨을 의미합니다.
* Selleck은 모든 화합물의 용해도를 자체적으로 테스트하며, 실제 용해도는 게시된 값과 약간 다를 수 있습니다. 이는 정상적인 현상이며, 약간의 배치 간 변동으로 인해 발생합니다.
* 실온 배송 (안정성 테스트 결과 이 제품은 냉각 조치 없이 배송될 수 있음을 보여줍니다.)

원액 준비

생물학적 활성

설명 PP-121은 PDGFR, Hck, mTOR, VEGFR2, Src 및 Abl을 표적으로 하는 다중 표적 억제제로, 각각 2 nM, 8 nM, 10 nM, 12 nM, 14 nM 및 18 nM의 IC50 값을 가지며, 60 nM의 IC50으로 DNA-PK도 억제합니다.
표적
PDGFR Hck VEGFR2 mTOR Src 더 보기
2 nM 8 nM 12 nM 13 nM 14 nM
시험관 내(In vitro)

PP-121 selectivity interacts within a hydrophobic pocket that is conserved between both tyrosine kinases and PI3Ks, not serine-threonine kinases. PP-121 makes a hydrogen bond to Glu310 in Src, effectively substituting for the structural role of the catalytic lysine and resulting in the ordering of helix C and stabilization of an active conformation. PP-121 also inhibits other PI3Ks including p110α and DNA-PK with IC50 of 52 nM and 60 nM, respectively. PP-121 potently and dose-dependently blocks the phosphorylation of Akt, p70S6K and S6 in two glioblastoma cell lines, U87 and LN229. PP-121 potently inhibits the proliferation of a subset of the tumor cell lines by direct inhibition of PI3Ks and mTOR. PP-121 induces a G0/G1 arrest in LN220, U87 and Seg1 cells. PP-121 also blocks tyrosine phosphorylation induced by v-Src in NIH3T3 cells transformed with v-Src(Thr338). PP-121 could restore actin stress fiber staining in NIH3T3 cells transformed with v-Src(Thr338). PP-121 at a low concentration of 40 nM inhibits Ret autophosphorylation in TT thyroid carcinoma cells that express the C634W oncogenic Ret mutant35. PP-121 inhibits cell proliferation with IC50 of 50 nM in TT thyroid carcinoma cells. PP-121 inhibits cell proliferating stimulated only with VEGF with IC50 of 41 nM in human umbilical vein endothelial cells (HUVECs). PP-121 directly inhibits Bcr-Abl induced tyrosine phosphorylation, resulting in drug-induced apoptosis in K562 cells and a combination of apoptosis and cell cycle arrest in Bcr-Abl expressing BaF3 cells.

프로토콜 (참조)

키나아제 분석:

[1]
  • Kinase 분석

    정제된 kinase 도메인을 1nM-50 µM 농도 범위에서 2배 또는 4배 희석된 PP121 또는 비히클(0.1% DMSO)과 함께 10 µM ATP, 2.5 µCi의 γ-32P-ATP 및 기질 존재 하에 인큐베이션합니다. 반응은 기질에 따라 니트로셀룰로오스 또는 포스포셀룰로오스 막에 점적하여 종료하며, 이 막을 5~6회 세척하여 결합되지 않은 방사능을 제거한 후 건조합니다. 전이된 방사능은 포스포이미징(phosphorimaging)으로 정량화하며, IC50 값은 Prism 소프트웨어를 사용하여 데이터를 시그모이드 용량-반응 곡선에 맞추어 계산합니다.
세포 분석:

[1]
  • 세포주

    U87, LN229, NIH3T3, HUVECs, BaF3 and TT thyroid carcinoma cells

  • 농도

    0.04-20 μM

  • 배양 시간

    24-72 hours

  • 방법

    For western blot analysis, cells are grown in 12-well plates and treated with PP-121 at the indicated concentrations or vehicle (0.1% DMSO). Treated cells are lysed, lysates are resolved by SDS-PAGE, transferred to nitrocellulose and blotted. For cell proliferation assays,cells are grown in 96-well plates are treated with PP-121 at 4-fold dilutions (10 µM - 0.040 μM) or vehicle (0.1% DMSO). After 72 hours cells are exposed to Resazurin sodium salt (22 µM) and fluorescence is quantified. IC50 values are calculated using Prism software. For proliferation assays involving single cell counting, non-adherent cells are plated at low density (3–5% confluence) and treated with PP-121 (2.5 µM) or vehicle (0.1% DMSO). Cells are diluted into trypan blue daily and viable cells counted using a hemocytometer. For apoptosis and cell cycle analysis, cells are treated with the indicated concentration of PP-121 or vehicle (0.1% DMSO) for 24–72 hours. Cells are either stained live with AnnexinV-FITC or fixed with ethanol and stained with propidium iodide. Cell populations are separated using a FacsCalibur flow cytometer; data is collected using CellQuest Pro software and analyzed with either ModFit or FlowJo Software.

참조

  • https://pubmed.ncbi.nlm.nih.gov/18849971/

고객 제품 검증

PP121 induces apoptosis in ATC cells. CAL62 cells were treated with PP121 at the indicated concentrations for 48 h, followed by PI staining. The nuclei were stained with Hoechst and analyzed using a fluorescent microscope. The representative images are shown.

데이터 출처 [ Tumour Biol , 2014 , 35(9), 8659-64 ]

<p>After starved in serum-free medium for 24 h,A549 cells incubated with the indicated concentrations of PP-121 for 3 h,followed by 20-minute stimolation of 100ng/ml EGF.</p>

, , Dr. Zhang of Tianjin Medical University

Selleck's PP121 인용됨 9 출판물

Inhibition of an Erythrocyte Tyrosine Kinase with Imatinib Prevents Plasmodium falciparum Egress and Terminates Parasitemia [ PLOS One, October 21, 2016, e0164895] PubMed: 27768734
c-Myc Alterations Confer Therapeutic Response and Acquired Resistance to c-Met Inhibitors in MET-Addicted Cancers [ Cancer Research, November 01, 2015, 4548-4559] PubMed: 26483207
FIREWORKS: a bottom-up approach to integrative coessentiality network analysis [ Life Sci Alliance, 2021, 4(2)e202000882] PubMed: 33328249
Discovery of Diverse Small-Molecule Inhibitors of Mammalian Sterile20-like Kinase 3 (MST3) [ ACS Chem Biol, 2016, 1446-1454] PubMed: 27135311
Inhibition of an Erythrocyte Tyrosine Kinase with Imatinib Prevents Plasmodium falciparum Egress and Terminates Parasitemia. [ PLoS One, 2016, 11(10):e0164895] PubMed: 27768734
The anti-esophageal cancer cell activity by a novel tyrosine/phosphoinositide kinase inhibitor PP121 [Peng Y, et al. Biochem Biophys Res Commun, 2015, 465(1):137-44] PubMed: 26235881
PP121, a dual inhibitor of tyrosine and phosphoinositide kinases, inhibits anaplastic thyroid carcinoma cell proliferation and migration [Che HY, et al. Tumour Biol, 2014, 35(9):8659-64] PubMed: 24867098
Systematic screen with kinases inhibitors reveals kinases play distinct roles in growth of osteoprogenitor cells [ Int J Clin Exp Pathol, 2013, 2082-2091] PubMed: 24133586
Systematic screen with kinases inhibitors reveals kinases play distinct roles in growth of osteoprogenitor cells [Bao NR, et al. Int J Clin Exp Pathol, 2013, 6(10):2082-91] PubMed: 24133586

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