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874146-69-7

中文名稱 PK11007;PK-11007;PK 11007
英文名稱 5-chloro-2-[(4-fluorophenyl)methylsulfonyl]-N-(5-methyl-1,3,4-thiadiazol-2-yl)pyrimidine-4-carboxamide
CAS 874146-69-7
分子式 C15H11ClFN5O3S2
分子量 427.86
MOL 文件 874146-69-7.mol
更新日期 2026/05/27 08:48:18
874146-69-7 結(jié)構(gòu)式 874146-69-7 結(jié)構(gòu)式

基本信息

中文別名
5-氯-2-((4-氟芐基)磺?;?-N-(5-甲基-1,3,4-噻二唑-2-基)嘧啶-4-甲酰胺
英文別名
PK11007
PK-11007
PK 11007
5-chloro-2-[(4-fluorophenyl)methylsulfonyl]-N-(5-methyl-1,3,4-thiadiazol-2-yl)pyrimidine-4-carboxamide
5-Chloro-2-[[(4-fluorophenyl)methyl]sulfonyl]-N-(5-methyl-1,3,4-thiadiazol-2-yl)-4-pyrimidinecarboxamide

物理化學性質(zhì)

密度1.610±0.06 g/cm3(Predicted)
儲存條件Sealed in dry,2-8°C
酸度系數(shù)(pKa)4.18±0.50(Predicted)
形態(tài)Solid
顏色White to off-white

安全數(shù)據(jù)

危險性符號(GHS)有害 (GHS07)
GHS07
警示詞警告
危險性描述H302-H315-H319-H335
PK11007;PK-11007;PK 11007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
2026/06/05HY-128784PK11007;PK-11007;PK 11007
PK11007
874146-69-71 mg394元
2026/06/05HY-128784PK11007;PK-11007;PK 11007
PK11007
874146-69-75 mg900元
2026/06/05HY-128784PK11007;PK-11007;PK 11007
PK11007
874146-69-710 mM * 1 mL in DMSO990元

常見問題列表

生物活性
PK11007 是具有抗癌活性的溫和硫醇烷基化劑。PK11007 通過兩個表面暴露的半胱氨酸的選擇性烷基化來穩(wěn)定 p53,而不影響其 DNA 結(jié)合活性。PK11007 通過增加活性氧 (ROS) 水平誘導突變的 p53 癌細胞死亡。
體外研究

PK11007 (0-120 μM; 24 hours; four p53 wild-type cell lines and fours p53 mutant cell lines) treatment results in a large viability reduction in mutant p53 cell lines MKN1 (V143A), HUH-7 (Y220C), NUGC-3 (Y220C), and SW480 (R273H/P309S) at concentrations ranging from 15 to 30 μM. PK11007 induces mainly caspase-independent cell death.
PK11007 (0-60 μM; 3 hours or 6 hours; NUGC-4, NUGC-3, MKN1, HUH-6, and HUH-7 cancer cells) treatment up-regulates protein levels of the p53 target genes p21, MDM2, and PUMA in a mostly concentration-dependent manner in NUGC-3 (p53-Y220C), HUH-7 (p53-Y220C) and MKN1 (p53-V143A) cells, suggesting partial restoration of transcriptional activity to destabilized p53 mutants. PK11007 also increases p53 activity in HUH-6 and NUGC-4 cells, as indicated by the increase of MDM2, PUMA, and p21 protein levels.
PK11007 (15-20 μM; 4.5 hours or 6 hours; MKN1, HUH-7, NUGC-3, HUH-6 cells) treatment increases transcription of p53 target genes in three mutant p53 cell lines after 6-h treatment. PUMA and p21 mRNA levels are up-regulated by a factor of 2 upon treatment of NUGC-3, MKN, and HUH-7 cells, as well as NOXA for the latter two. MDM2 levels are halved in MKN1 and NUGC-3 cells.
PK11007 viability reduction is potentiated by glutathione depletion. To test whether PK11007 also increases ROS levels, NUGC-3, NUGC-4, HUH-6, HUH-7, and MKN1 cells with PK11007 are incubated for 2 h. There are elevated ROS levels in all cell lines after 2 h. In the mutant p53 cells MKN1, HUH-7, and NUGC-3, however, the ROS increase is higher at 60 μM PK11007 than in NUGC-4 and HUH-6 cells, suggesting that the higher PK11007 sensitivity of the mutant p53 cell lines is mediated by a stronger ROS induction. Basal and PK11007-induced ROS levels in MKN1 cells are at least twofold higher than in other cell lines.
PK11007 inhibits cell proliferation, induces apoptosis and alters genes involved in cell death are all consistent with the ability of PK11007 to reactivate mutant p53.

Cell Viability Assay

Cell Line: p53 wild-type cell lines (WI-38, HUH-6, NUGC-4, SJSA-1) and p53 mutant cell lines (HUH-7, NUGC-3, SW480, MKN1)
Concentration: 0 μM, 20 μM, 40 μM, 60 μM, 80 μM, 100 μM and 120 μM
Incubation Time: 24 hours
Result: There was a large viability reduction in mutant p53 cell lines MKN1 (V143A), HUH-7 (Y220C), NUGC-3 (Y220C), and SW480 (R273H/P309S) and in p53 WT cell line SJSA-1 at concentrations ranging from 15 to 30 μM. The p53 WT cancer cell lines HUH-6, NUGC-4 and WI-38 were less sensitive with reduced cell viability only at high concentrations of compound (60 and 120 μM).

Western Blot Analysis

Cell Line: NUGC-4, NUGC-3, MKN1, HUH-6, and HUH-7 cancer cells
Concentration: 0 μM, 15 μM, 30 μM, 60 μM
Incubation Time: 3 hours or 6 hours
Result: Up-regulated protein levels of the p53 target genes p21, MDM2, and PUMA in a mostly concentration-dependent manner in NUGC-3 (p53-Y220C), HUH-7 (p53-Y220C) and MKN1 (p53-V143A) cells. Also increased p53 activity in HUH-6 and NUGC-4 cells, as indicated by the increase of MDM2, PUMA, and p21 protein levels.

RT-PCR

Cell Line: MKN1, HUH-7, NUGC-3, HUH-6 cells
Concentration: 15 μM, 20 μM
Incubation Time: 4.5 hours or 6 hours
Result: Increased transcription of p53 target genes in three mutant p53 cell lines after 6-h treatment. PUMA and p21 mRNA levels were up-regulated by a factor of 2 upon treatment of NUGC-3, MKN, and HUH-7 cells, as well as NOXA for the latter two. MDM2 levels were halved in MKN1 and NUGC-3 cells.
"874146-69-7" 相關(guān)產(chǎn)品信息
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