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891494-63-6

中文名稱 6-溴-3-(1-甲基-1H-吡唑-4-基)-5-(3R)-3-哌啶基吡唑并[1,5-A]嘧啶-7-胺
英文名稱 SCH900776
CAS 891494-63-6
分子式 C15H18BrN7
分子量 376.254
MOL 文件 891494-63-6.mol
更新日期 2023/03/20 15:41:23
891494-63-6 結(jié)構(gòu)式 891494-63-6 結(jié)構(gòu)式

基本信息

中文別名
化合物MK-8776
SCH900776(S型)
SCH900776(R型)
6-溴-3-(1-甲基-1H-吡唑-4-基)-5-(3R)-3-哌啶基吡唑并[1,5-A]嘧啶-7-胺
英文別名
SCH900776(R)
SCH 900776, >=98%
SCH900776 USP/EP/BP
SCH 900776 (MK-8776)
MK-8776 (SCH 900776)
MK-8776 (SCH900776)(S)
SCH-900776
SCH 900776
MK-8776.
6-Bromo-3-(1-methyl-1H-pyrazol-4-yl)-5-(3R)-3-piperidinylpyrazolo[1,5-a]pyrimidin-7-amine
(R)-6-Bromo-3-(1-methyl-1H-pyrazol-4-yl)-5-(piperidin-3-yl)pyrazolo[1,5-a]pyrimidin-7-amine
6-bromo-3-(1-methyl-1H-pyrazol-4-yl)-5-((R)-piperidin-3-yl)pyrazolo[1,5-a]pyrimidin-7-amine
所屬類別
生物化工:Chk 抑制劑

物理化學(xué)性質(zhì)

密度1.80
儲存條件-20°C儲存
溶解度insoluble in H2O; insoluble in EtOH; ≥18.8 mg/mL in DMSO
酸度系數(shù)(pKa)8.88±0.10(Predicted)
形態(tài)結(jié)晶固體
顏色White to off-white

常見問題列表

生物活性
MK-8776 (SCH 900776)是一種選擇性Chk1抑制劑,IC50為3 nM,比作用于Chk2選擇性高50倍。Phase 2。
體外研究
SCH 900776 is not a potent inhibitor of Chk2 and CDK2 with IC50 of 1.5 μM and 0.16 μM, respectively. SCH 900776 shows no significant inhibition of cytochrome P450 human liver microsomal isoforms 1A2, 2C9, 2C19, 2D6, and 3A4. SCH 900776 induces a dose-dependent loss of DNA replication capability 24 hours after hydroxyurea exposure. SCH 900776 enhances the γ-H2AX response of hydroxyurea, 5-fluoruracil, and cytarabine. In combination with an antimetabolite, SCH 900776 induces accumulation of γ-H2AX within 2 hours, indicative of replication fork collapse and double stranded DNA breaks. Additionally, SCH 900776 suppresses accumulation of the Chk1 pS296 autophosphorylation in a dose-dependent manner. Exposure of proliferating WS1 cells to SCH 900776 is associated with rapid, dose-dependent accumulation of Chk1 pS345, indicating that cycling populations of normal cells induce Chk1 pS345 following exposure to SCH 900776 as part of a futile cycle, perhaps driven by AT-family kinases and DNA-PK.
體內(nèi)研究
Administered 30 minutes after gemcitabine, 4 mg/kg SCH 900776 is sufficient to induce the γ-H2AX biomarker while 8 mg/kg leads to enhanced tumor pharmacodynamic and regression responses relative to gemcitabine or SCH 900776 alone. Dose escalation of SCH 900776 (16 mg/kg and 32 mg/kg) induces incremental improvements in tumor response. Importantly, doses of SCH 900776 associate with robust biomarker activation and improved tumor response are not associated with enhanced toxicity of gemcitabine on hematological parameters in BALB/c mice.
生物活性
MK-8776 (SCH 900776)是一種選擇性Chk1抑制劑,無細(xì)胞試驗中IC50為3 nM,比作用于Chk2選擇性高500倍。Phase 2。
靶點
TargetValue
Chk1
(Cell-free assay)
3 nM
CDK2
(Cell-free assay)
0.16 μM
體外研究

SCH 900776是Chk2和CDK2的低效抑制劑,IC50分別為1.5 μM 和 0.16 μM。SCH 900776對細(xì)胞色素P450人肝微粒體亞型1A2,2C9,2C19,2D6,和3A4沒有顯著的抑制作用。羥基脲下暴露24小時后,SCH 900776誘導(dǎo)DNA復(fù)制能力劑量依賴性損失。SCH 900776增強(qiáng)γ-H2AX對羥基脲,5-氟尿嘧啶,和阿糖孢苷的響應(yīng)。與抗代謝物結(jié)合,SCH 900776在2小時內(nèi)誘導(dǎo)γ-H2AX的累積,表明復(fù)制叉瓦解,并且雙鏈DNA斷裂。此外,SCH 900776以劑量依賴的方式抑制Chk1 pS296自磷酸化的積累。增殖的WS1細(xì)胞暴露于SCH 900776,與Chk1 pS345快速的,劑量依賴性聚集相關(guān),表明正常細(xì)胞的循環(huán)群誘導(dǎo)Chk1 pS345在暴露于SCH 900776后,是一部分無效循環(huán),這也許通過AT-家族激酶和DNA-PK驅(qū)動。

體內(nèi)研究
相對于gemcitabine或SCH 900776單獨給藥,Gemcitabine給藥30分鐘后,4 mg/kg SCH 900776足以誘導(dǎo)γ-H2AX生物標(biāo)志物,而8 mg/kg增強(qiáng)腫瘤藥效動力學(xué)和退化響應(yīng)。遞增劑量的SCH 900776 (16 mg/kg和32 mg/kg)誘導(dǎo)腫瘤響應(yīng)持續(xù)改進(jìn)。重要的是,在BALB/c 小鼠體內(nèi),SCH 900776的劑量與強(qiáng)的生物標(biāo)志物活化相關(guān),而提高的腫瘤響應(yīng)與gemcitabine對血液學(xué)指標(biāo)增強(qiáng)的毒性無關(guān)。
6-溴-3-(1-甲基-1H-吡唑-4-基)-5-(3R)-3-哌啶基吡唑并[1,5-A]嘧啶-7-胺價格(試劑級)
報價日期產(chǎn)品編號產(chǎn)品名稱CAS號包裝價格
2024/11/08S27356-溴-3-(1-甲基-1H-吡唑-4-基)-5-(3R)-3-哌啶基吡唑并[1,5-A]嘧啶-7-胺
MK-8776 (SCH 900776)
891494-63-65mg1733.35元
2024/11/08S27356-溴-3-(1-甲基-1H-吡唑-4-基)-5-(3R)-3-哌啶基吡唑并[1,5-A]嘧啶-7-胺
MK-8776 (SCH 900776)
891494-63-610mM(1mL in DMSO)1921.21元
2024/11/08S27356-溴-3-(1-甲基-1H-吡唑-4-基)-5-(3R)-3-哌啶基吡唑并[1,5-A]嘧啶-7-胺
MK-8776 (SCH 900776)
891494-63-610mg3015.42元
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