1、倘(琀币匀爀币币琀币讀缁缀劙漁螏頀h椀霂褃匃匈匈漈茈謈謈謈嘀一一刀攀搀栀攀洀砀瀀爀攀猀猀瀀搀昀瀀椀挀最椀昀嘀一一刀攀搀栀攀洀砀瀀爀攀猀猀瀀搀昀尀尀戀昀搀昀挀挀攀攀昀愀攀戀愀挀儀猀一栀砀愀最椀堀儀嘀瀀唀搀眀氀挀堀匀伀猀洀堀嘀唀倀琀昀栀堀眀刀欀爀甀稀樀瘀眀嘀一一刀攀搀栀攀洀砀瀀爀攀猀猀愀挀昀愀昀挀攀挀搀瀀瀀洀琀愀琀攀甀最漀挀甀洀攀渀琀猀吀椀琀氀攀愀琀愀氀漀最一漀夀愀琀挀栀匀瀀攀挀琀爀甀洀吀椀琀氀攀夀开娀圀夀儀爀攀焀甀攀渀挀礀稀昀伀爀椀最椀渀愀氀倀漀椀渀琀猀漀甀渀琀昀挀琀甀愀氀倀漀椀渀琀猀漀甀渀琀昀挀焀甀椀猀椀琀椀漀渀吀椀洀攀猀攀挀昀匀瀀攀挀琀爀愀氀圀椀搀琀栀瀀瀀洀昀倀甀氀猀攀倀爀漀最爀愀洀唀渀欀渀
2、漀眀渀匀愀洀瀀氀攀娀圀夀儀愀琀愀氀漀最一漀夀愀琀挀栀匀伀匀伀伀一一一一一栀攀洀椀挀愀氀漀爀洀甀氀愀一伀匀砀愀挀琀愀猀猀攀搀栀攀洀砀瀀爀攀猀猀靓辉退舀祒茤佦蠀懈!牁鄃凍艉芓蕞庂膅!牁鄃凍蝉芓蕞庂膅!牁鄃勍艑芓皫腶!牁鄃勍蝑芓皫腶!鄊勍芛芓琀挛匜褛鬛猞鄚1芪!騀苻1鳚芬!攀倐猠舐魒鎇者跥t鴡蠡裭頀苙!頀苻!芜!鏟!e瀐酐魒嵗鎂苤魒嵗鎇苤灓鎂苅灓鎇苅鄀鎂艡仉偐İ!跮鰀!鄅反蟠芓懒荎!馜鎂肅藎牁鄄囍蟴肓藎膅!脀譗鎂脶鬏+苯鬡頞鰘譗鎇脶鬏+苯鬡頞鰘腐鎂嚂胴,騱臈!脀舐脐鄊姍蜍芓褍踡灰怐鄊姍舧芓贄褙蠡抺輛雾鈡拝抚鏝蓈輐铿鼡鸟努鬡!倄鉐脐怐灠瀠【灀鄰怐偰灀偀Q|鄊姍蜧芓贄褙蠡抺輛雾鈡拝抚鏝蓈輐铿鼡鸟努鬡!倄
3、艐偀怐【Lw鄅巍若芓庁茨辍闞鎇脰辍!牁鄄巍以舚肓膾1脀鎇肾虞鎂鈃臖贜頡勍叹臹爛颙鯩釸拏輚萡訡力勎鐡贱香謟蒫舟蠐蓛踡拏鸐霝蔱鄘鬜覜頡勹裘鬐鄡袚鋏頡拪鼏势挚h倁倠恠恠恠恠恠扠恠恠恠扠倰偐偀瀐瀁倠倐唀紀省鼁朂鄂尃虞鎇鈃臖贜頡勍勹醹臸餉鏊馮輡鯹鼏蘡鰡力勎鐡贡香膽蒫钺犎谛谐钿拏霝蔡鄘鬜覜頡闿兄(币搀爀币币币讀缁缀劜漁螏頀h椀圃圃圃霃匀愀琀愀匀栀攀攀琀攀搀栀攀洀砀瀀爀攀猀猀瀀搀昀瀀椀挀最椀昀匀愀琀愀匀栀攀攀琀攀搀栀攀洀砀瀀爀攀猀猀瀀搀昀尀尀愀戀戀挀搀搀戀戀攀戀攀昀挀愀昀伀洀搀攀氀匀搀嘀圀爀刀戀椀爀欀唀渀漀戀椀爀砀唀儀最最椀刀瘀最眀匀愀琀愀匀栀攀攀琀攀搀栀攀洀砀瀀爀攀猀猀昀戀愀昀攀昀昀挀搀Z屇攀搀栀攀洀砀瀀
4、爀攀猀猀靓 schedule (100-300 mpk) or a twice a day schedule (50, 100 mpk) demonstrates antitumor activity in this tumor model. Oral glucose tolerance test (OGTT) shows 100 mpk (b.i.d.) causes a significant DescriptionProduct Data Sheet InhibitorsAgonistsScreening Librarieswww.MedChemE1elevation in glucos
5、e levels after glucose challenge. The pharmacokinetic parameters of BMS-536924, administered orally in poly(ethylene glycol) 400 and water (80:20 v/v), are determined in mouse, rat, dog, and monkey. Good bioavailability is evident in all species. Significant nonlinear pharmacokinetics is observed in
6、 rodents at increasing p.o. dose 1. Oral administration of 70 mg/kg BMS-536924 significantly inhibits tumor growth (TGBC-1TKB cells) inoculated in nude mice. BMS-536924 up regulates apoptosis in xenografts tumors. The treatment doesnt have adverse effects on the body weight of mice or the glucose le
7、vels at the time of death, suggesting tolerable toxicity 3.REFERENCES1. Wittman M, et al. Discovery of a (1H-benzoimidazol-2-yl)-1H-pyridin-2-one (BMS-536924) inhibitor of insulin-like growth factor I receptor kinase with in vivo antitumor activity. J Med Chem. 2005 Sep 8;48(18):5639-43.2. Litzenbur
8、ger BC, et al. BMS-536924 reverses IGF-IR-induced transformation of mammary epithelial cells and causes growth inhibition and polarization of MCF7 cells. Clin Cancer Res. 2009 Jan 1;15(1):226-37.3. Ohashi H, et al. Insulin-like growth factor receptor expression is associated with aggressive phenotyp
9、es and has therapeutic activity in biliary tract cancers. Cancer Sci. 2012 Feb;103(2):252-61.Caution: Product has not been fully validated for medical applications. For research use only.Tel: 609-228-6898 Fax: 609-228-5909 E-mail: techMedChemEAddress: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 0
10、8852, USAwww.MedChemE2MedChemExpress0001500006先进医疗20190531141510815982辉退舀祒茤佦蠀懈!牁鄃凍艉芓蕞庂膅!牁鄃凍蝉芓蕞庂膅!牁鄃勍艑芓皫腶!牁鄃勍蝑芓皫腶!鄊勍芛芓琀挛匜褛鬛猞鄚1芪!騀苻1鳚芬!攀倐猠舐魒鎇者跥t鴡蠡裭頀苙!頀苻!芜!鏟!e瀐酐魒嵗鎂苤魒嵗鎇苤灓鎂苅灓鎇苅鄀鎂艡仉偐İ!跮鰀!鄅反蟠芓懒荎!馜鎂肅藎牁鄄囍蟴肓藎膅!脀譗鎂脶鬏+苯鬡頞鰘譗鎇脶鬏+苯鬡頞鰘腐鎂嚂胴,騱臈!脀舐脐鄊姍蜍芓褍踡灰怐鄊姍舧芓贄褙蠡抺輛雾鈡拝抚鏝蓈輐铿鼡鸟努鬡!倄鉐脐怐灠瀠【灀鄰怐偰灀偀Q|鄊姍蜧芓贄褙蠡抺輛雾鈡拝抚鏝蓈輐铿鼡鸟努鬡!倄艐
11、偀怐【Lw鄅巍若芓庁茨辍闞鎇脰辍!牁鄄巍以舚肓膾1脀鎇肾虞鎂鈃臖贜頡勍叹臹爛颙鯩釸拏輚萡訡力勎鐡贱香謟蒫舟蠐蓛踡拏鸐霝蔱鄘鬜覜頡勹裘鬐剰匀(币匀爀币瀂币币讀缁缀功漁螏頀h椀！嬃嬃嬃鬃夙夙夙夙夙夙夙夙夙夙夙夙夙夙夙夙夙夙嬙匀匀攀搀栀攀洀砀瀀爀攀猀猀瀀搀昀瀀椀挀最椀昀匀匀攀搀栀攀洀砀瀀爀攀猀猀瀀搀昀尀尀昀搀搀昀戀挀搀昀愀愀搀攀琀眀刀瀀儀堀最攀氀娀伀礀倀琀戀最嘀焀伀儀伀欀甀吀爀渀漀一氀搀漀椀礀最匀匀攀搀栀攀洀砀瀀爀攀猀猀攀攀搀昀昀戀昀愀戀昀攀昀椀氀攀尀尀尀吀尀倀尀倀吀最琀愀猀猀娀堀渀樀攀挀琀椀漀渀愀琀攀愀渀瀀洀匀攀焀椀渀攀匀愀洀瀀氀攀一愀洀攀倀漀挀愀琀椀漀渀倀挀焀伀瀀攀爀愀琀漀爀娀娀开渀樀匀瀀攀挀刀
12、攀瀀漀爀琀攀搀匀渀琀攀最爀愀琀椀漀渀渀樀嘀漀氀甀洀攀甀氀挀焀攀琀栀漀搀尀栀攀洀尀尀吀伀匀尀倀伀匀一渀愀氀礀猀椀猀攀琀栀漀搀尀尀尀吀伀匀尀夀开尀匀夀开倀伀愀琀愀氀漀最一漀夀愀琀挀栀愀猀礀挀挀攀猀猀攀琀栀漀搀倀伀匀一攀琀栀漀搀渀昀漀倀漀猀琀椀瘀攀匀漀氀甀洀渀刀倀洡椀渀洀唀匀椀最刀攀昀漀昀昀洀椀渀洀唀匀椀最刀攀昀漀昀昀洀椀渀匀吀匀椀氀攀匀倀倀漀猀匀挀愀渀爀愀最洀椀渀漀渀匀吀愀爀最攀琀愀猀猀倀漀猀椀琀椀瘀攀渀琀攀最爀愀琀椀漀渀刀攀猀甀氀琀猀昀漀爀匀椀最刀攀昀漀昀昀刀攀琀吀椀洀圀椀搀琀栀爀攀愀攀椀最栀琀爀攀愀匀簀簀簀簀簀簀簀渀琀攀最爀愀琀椀漀渀刀攀猀甀氀琀猀昀漀爀匀椀最刀攀昀漀昀昀刀攀琀吀椀洀圀椀搀琀栀
13、爀攀愀攀椀最栀琀爀攀愀匀簀簀簀簀簀簀簀匀刀攀瀀漀爀琀昀爀漀洀渀猀琀爀甀洀攀渀琀夀匀夀匀倀娀娀开倀愀最攀漀昀刀攀琀吀椀洀攀最琀最琀最琀洀稀匀倀倀漀猀椀琀椀瘀攀匀刀攀瀀漀爀琀昀爀漀洀渀猀琀爀甀洀攀渀琀夀匀夀匀倀娀娀开倀愀最攀漀昀攀搀栀攀洀砀瀀爀攀猀猀靓怡褀氀速刀昀扏很鎂庂芅蕞鎇庂芅蕞兒鎂艶皫兒鎇艶皫魒鎂者跥t鴱蠱裭頀苙1頀苻!芜!鏟!e:鄊勍螛芓琀戛刜褛鬛猞鄚1芪!騀苻!鳚芬!攀瀐舠倐瀠鄐鄀脀脀6牁鄃勍垛艝芓臤!牁鄃勍垛蝝芓臤!鄅反艰肓!鄅反蝰肓!鄅反苠芓懒荎倀!馜鎇艡仉İ!跮鰀嗴需(币匀币币币讀缁缀劣漁螏頀h椀褂猃匀匀匀攀搀栀攀洀砀瀀爀攀猀猀瀀搀昀瀀椀挀最椀昀匀匀匀攀搀栀攀洀砀瀀爀攀猀猀瀀搀昀尀
14、尀搀戀攀昀攀愀挀戀攀挀搀愀搀搀漀瘀洀戀焀瀀砀甀匀砀儀甀漀洀椀儀吀洀伀圀爀礀爀夀稀昀瀀渀瀀琀搀儀匀匀匀攀搀栀攀洀砀瀀爀攀猀猀挀攀昀挀戀攀愀攀搀挀攀愀攀愀戀昀Z栀琀甀R瘀攀搀栀攀洀砀瀀爀攀猀猀靓言茀渀7琀币琻:寐軘筴寐胔-輀棙i缀$BMS-599626-DataSheet-MedChemExpress.pdfpic1.gifBMS599626DataSheetMedChemExpress.pdf2019-531a9851a34-7c44-465b-8968-ae78fecb309086J9M83A2dIUWfCfqnF9rFDHpCZUCPg3LGRLh7kCbOW5ypU5E5zgRQ=BMS,
15、599626,DataSheet,MedChemExpress3cf52023eb5f64728a3cd760c6559109BMS-599626Cat. No.: HY-10251CAS No.: 714971-09-2Molecular Formula: CHFNOMolecular Weight: 530.55Target: EGFRPathway: JAK/STAT Signaling; Protein Tyrosine Kinase/RTKStorage: Please store the product under the recommended conditions in the
16、 COA.Solvent 30 nM (HER2) 1Target: HER1/HER2in vitro: BMS-599626 inhibited HER1 and HER2 with IC50 of 20 and 30 nmol/L, respectively, and was highly selective when tested against a broad panel of diverse protein kinases. Biochemical studies suggested that BMS-599626 inhibited HER1 and HER2 through d
17、istinct mechanisms. BMS-599626 abrogated HER1 and HER2 signaling and inhibited the proliferation of tumor cell lines that are dependent on these receptors, with IC50 in the range of 0.24 to 1 micromol/L. BMS-599626 was highly selective for tumor cells that depend on HER1/HER2 and had no effect on th
18、e proliferation of cell lines that do not express these receptors. In tumor cells that are capable of forming HER1/HER2 heterodimers, BMS-599626 inhibited heterodimerization and downstream signaling 1. At the molecular level, in HN-5 cells the agent inhibited the expression of pEGFR, pHER2, cyclins
19、D and E, pRb, pAkt, pMAPK, pCDK1 and 2, CDK 6, and Ku70 proteins. The drug also induced accumulation of cells in the G1 cell cycle phase, inhibited cell growth, enhanced radiosensitivity, and prolonged the presence of -H AX foci up to 24 h after radiation 2.in vivo: BMS-599626 had antitumor activity
20、 in models that overexpress HER1 (GEO), as well as in models that have HER2 gene amplification (KPL4) or overexpression (Sal2), and there was good correlation between the inhibition of receptor signaling and antitumor activity 1. The drug given before and during irradiation improved the radioresponse of HN5 tumors in vivo 2.Product Data Sheet InhibitorsAgonistsScreening Librarieswww.MedChemE1REFERENCES1. Wong TW, et al. Preclinical antitumor activity of BMS-599626, a pan-HER kinase inhibitor that in
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