Thiostrepton

Thiostrepton|FOXM1 inhibitor|YAP/TEAD/FOXM1 complex|Antitumor peptide|Kev tshawb fawb-Peptide

【Properties】 Dawb los yog tawm -dawb hmoov
【Purity】 Ntau dua lossis sib npaug li 95%
【Package】 5mg, 10mg
【Storage】 2-8 degree, Cia -20 degree, kaw cia
【Cov Lus Qhia Ntxiv] Peptide nqe, cov ntaub ntawv sib txuas, cov qauv tshuaj, qhov hnyav molecular, cov ntaub ntawv tshawb fawb tshawb fawb, thov email nug

Thiostrepton (TST), thiazole cyclic peptide tshuaj tua kab mob los ntawm Streptomyces, tsis ntev los no tau raug txheeb xyuas tias yog ib qho tshwj xeeb inhibitor ntawm transcription factor FOXM1, uas yog ib qho tseem ceeb oncogene transcription yam uas tswj cell voj voog mus, genome stability, thiab DNA kho, thiab yog heev nthuav tawm nyob rau hauv ntau yam qog nqaij hlav, thiab yog ze rau cov tshuaj tiv thaiv kab mob. Cov tshuaj no txuas ncaj qha rau FOXM1 cov protein, txo nws cov kev ua haujlwm transcriptional, thiab qis dua - tswj FOXM1 kev qhia ntawm qib transcriptional thiab txhawb nqa; FOXM1 khi rau YAP/TEAD transcriptional complex, thiab ua ke lawv ua si ib tug transcriptional lub luag hauj lwm nyob rau hauv cov kev tswj cheeb tsam ntawm lub voj voog ntawm tes- tswj cov noob, cuam tshuam cov cell proliferation. Raws li cov txheej txheem saum toj no, cov tshuaj tua kab mob no qhia ntau yam kev siv hauv kev tshawb fawb los tiv thaiv- qog.

Kawm txog cov txheej txheem ntawm lub hom phiaj ncaj qha ntawm FOXM1
Ib txoj kev tshawb fawb luam tawm hauv Nature Chemistry hauv xyoo 2011 tau pom tias Thiostrepton cuam tshuam ncaj qha nrog FOXM1 protein hauv tib neeg lub mis mob qog noj ntshav MCF-7. Biophysical tsom xam pom tias nws khi tshwj xeeb rau FOXM1 thiab inhibits kev khi ntawm FOXM1 rau genomic lub hom phiaj hauv kev soj ntsuam ntawm tes. Txoj kev tshawb no yog thawj zaug los piav qhia txog hom kev ua ntawm qhov sib xyaw no hauv kev tsom FOXM1 ntawm qib molecular. Lwm txoj kev tshawb fawb tau qhia tias nws txo qis - tswj FOXM1 protein ntau ntau los ntawm redox-dependent thiab proteasome- cov txheej txheem nyob, thiab kev tswj qis tau tiv thaiv los ntawm antioxidant NAC thiab proteasome inhibitor MG132.

YAP/TEAD/FOXM1 transcription complex studies
Ib txoj kev tshawb fawb 2017 luam tawm nyob rau hauv Gastroenterology pom tias nyob rau hauv hepatocellular carcinoma hlwb, YAP / TEAD4 tsav chromosomal instability noob qhia profiles los ntawm induction thiab khi ntawm FOXM1. Inhibition ntawm FOXM1 nrog Thiostrepton los yog blockade ntawm YAP-TEAD4 cuam tshuam nrog Verteporfin txo cov chromosomal instability noob qhia qauv. Kev txhaj tshuaj ntawm tus neeg sawv cev no hauv YAPS127A cov nas transgenic txo qis daim siab kev loj hlob thiab cov cim qhia ntawm chromosomal instability, qhia tias lub hom phiaj no yuav yog lub tswv yim tshiab rau kev kho mob hepatocellular carcinoma.

Induction ntawm cell voj voog ntes thiab kev tshawb fawb apoptosis
Thiostrepton tau xaiv ua rau mob qog noj ntshav hauv lub cev raug ntes hauv G₁ thiab S theem thiab ua rau kev tuag ntawm tes los ntawm nqes- kev tswj hwm ntawm FOXM1, thaum nws tsis muaj kev cuam tshuam rau FOXM1 kev qhia thiab kev loj hlob nyob rau hauv uas tsis yog - hloov MCF -10A mammary epithelial cell, qhia cov kab mob toxicity. Hauv laryngeal squamous cell carcinoma (LSCC), qhov sib xyaw no inhibited cell viability nyob rau hauv ib koob- thiab lub sij hawm-nyob raws li, induced S-phase cell voj voog ntes thiab DNA synthesis inhibition, thiab induced apoptosis ntawm mitochondria-dependent1}caspase thiab { extrinsic txoj kev. Nyob rau hauv ib tug liab qab nas LSCC xenograft qauv, kev kho mob nrog cov tshuaj tua kab mob no inhibited tumorigenesis, proliferation thiab induced apoptosis.

Triple negative mis cancer (TNBC) txoj kev tshawb fawb
Hauv MDA-MB-231 TNBC hlwb, Thiostrepton induced mitotic spindle abnormalities, mitotic ntes, thiab apoptotic cell tuag, ho txhim kho paclitaxel cytotoxicity, thiab tseem zoo nyob rau hauv paclitaxel-resistant cell kab. Ib txoj kev tshawb fawb 2022 tau pom tias tus neeg sawv cev no ib leeg ua rau muaj qhov cuam tshuam loj heev ntawm cov qog nqaij hlav, lub ntsws metastasis, thiab tus naj npawb ntawm cov qog foci hauv 4T1 TNBC syngeneic hloov qauv, thiab inhibited FoxM1 qhia.

Kev siv tshuaj sib xyaw ua ke thiab kev tshawb nrhiav tshuaj tiv thaiv rov qab
Thiostrepton, ua ke nrog PARP inhibitor Olaparib, ua rau txo qis hauv cell viability nyob rau hauv cov qog nqaij hlav cancer ntawm lub mis los ntawm kev nce DNA ob npaug -strand so dua li ib tus neeg sawv cev. Hauv kev siv tshuaj khomob- tiv thaiv qog noj ntshav ntawm zes qe menyuam, qhov sib xyaw ua ke no txo ​​qis- tswj FOXM1 thiab nws cov phiaj xwm qis qis CCNB1 thiab CDC25B, thiab pom muaj kev sib koom ua ke nrog paclitaxel thiab cisplatin. Tsis tas li ntawd, nws txo qis - tswj kev qhia ntawm osteosarcoma qia cell markers thiab txhim kho cov tshuaj rhiab heev rau cisplatin.

Tshawb nrhiav lwm hom qog nqaij hlav
Thiostrepton txhawb kev tiv thaiv- qog lub cev tiv thaiv kab mob hauv intrahepatic cholangiocarcinoma los ntawm FOXM1-kev kho mob ntawm cov qog uas cuam tshuam nrog macrophages polarized mus rau M1 phenotype. Hauv kev mob plab hnyuv, inhibition ntawm FOXM1-induced oxidative stress, autophagy thiab apoptosis ua rau qeeb cell proliferation, tsiv teb tsaws, ntxeem tau thiab angiogenesis. Hauv cov qauv xenograft subcutaneous ntawm pancreatic cancer, 17 mg / kg kev kho mob nrog cov tshuaj tua kab mob no cuam tshuam cov qog loj hlob.