- 抑制劑
- 研究領(lǐng)域
- PI3K/Akt/mTOR信號(hào)通路
- 表觀遺傳
- 甲基化
- 免疫&炎癥
- 酪氨酸蛋白激酶
- 血管生成
- 凋亡
- 自噬
- 內(nèi)質(zhì)網(wǎng)應(yīng)激&UPR響應(yīng)
- JAK/STAT信號(hào)通路
- MAPK信號(hào)通路
- 細(xì)胞骨架
- 細(xì)胞周期
- TGF-beta/Smad信號(hào)通路
- DNA損傷/DNA修復(fù)
- 化合物庫
- 抗體
- 生物試劑
- qPCR
- 2x SYBR Green qPCR Master Mix
- 2x SYBR Green qPCR Master Mix(Low ROX)
- 2x SYBR Green qPCR Master Mix(High ROX)
- 蛋白實(shí)驗(yàn)
- Protein A/G免疫沉淀磁珠
- Anti-DYKDDDDK Tag免疫磁珠
- Anti-DYKDDDDK Tag親和凝膠
- Anti-Myc免疫磁珠
- Anti-HA免疫磁珠
- 磁力架
- Poly DYKDDDDK Tag多肽
- 細(xì)胞核與細(xì)胞漿蛋白抽提試劑盒
- 免疫磁珠
- 蛋白酶抑制劑Cocktail
- 蛋白酶抑制劑Cocktail(DMSO儲(chǔ)液)
- 磷酸酶抑制劑Cocktail
- 細(xì)胞實(shí)驗(yàn)
- Cell Counting Kit-8 (CCK-8)
- 動(dòng)物實(shí)驗(yàn)
- 鼠尾直接PCR試劑盒(快速基因型鑒定)
- 小鼠CD3+ T細(xì)胞分選試劑盒
- 小鼠CD4+ T細(xì)胞分選試劑盒
- 小鼠CD8+ T細(xì)胞分選試劑盒
- 新產(chǎn)品
- 聯(lián)系我們
Neratinib (HKI-272)
別名: HKI-272
Neratinib是一種高度選擇性的HER2和EGFR抑制劑，在無細(xì)胞試驗(yàn)中IC50分別為59 nM 和 92 nM；微弱抑制KDR和Src，對(duì)Akt，CDK1/2/4，IKK-2，MK-2，PDK1，c-Raf和c-Met沒有顯著的抑制作用。Phase 3。
Neratinib (HKI-272) Chemical Structure
CAS: 698387-09-6
產(chǎn)品質(zhì)控
批次：
純度：
99.94%
99.94
Neratinib (HKI-272)相關(guān)產(chǎn)品
| 相關(guān)產(chǎn)品 | CP-724714 Sapitinib (AZD8931) Mubritinib (TAK 165) AC480 (BMS-599626) Tyrphostin AG 879 HER2-Inhibitor-1 TAS0728 | 點(diǎn)擊展開 |
|---|---|---|
| 相關(guān)化合物庫 | 激酶抑制劑庫 酪氨酸激酶抑制劑分子庫 PI3K/Akt 抑制劑庫 細(xì)胞周期化合物庫 血管生成相關(guān)化合物庫 | 點(diǎn)擊展開 |
相關(guān)信號(hào)通路圖
細(xì)胞實(shí)驗(yàn)數(shù)據(jù)示例
| 細(xì)胞系 | 實(shí)驗(yàn)類型 | 給藥濃度 | 孵育時(shí)間 | 活性描述 | 文獻(xiàn)信息(PMID) |
|---|---|---|---|---|---|
| SKBR | Growth Inhibition Assay | 0.01-100 nM | 3-7 d | inhibits cell growth in time and dose dependent manner | 21487605 |
| Sf9 | Function assay | 10 mins | Inhibition of human wild type EGFR expressed in Sf9 cells using [gamma32P]-ATP after 10 mins by scintillation counting, IC50 = 0.0025 μM. | 24900643 | |
| Sf9 | Function assay | 10 mins | Inhibition of human EGFR T790M/L858R mutant expressed in Sf9 cells using [gamma32P]-ATP after 10 mins by scintillation counting, IC50 = 0.066 μM. | 24900643 | |
| BAF3 | Function assay | 72 hrs | Inhibition of Tel-fused IGF1R (unknown origin) expressed in mouse BAF3 cells assessed as growth inhibition after 72 hrs by CellTiter-Glo assay, GI50 = 0.19 μM. | 28282122 | |
| BAF3 | Function assay | 72 hrs | Inhibition of Tel-fused INSR (unknown origin) expressed in mouse BAF3 cells assessed as growth inhibition after 72 hrs by CellTiter-Glo assay, GI50 = 0.29 μM. | 28282122 | |
| BAF3 | Growth inhibition assay | 72 hrs | Growth inhibition of mouse BAF3 cells after 72 hrs by CellTiter-Glo assay, GI50 = 1.9 μM. | 28282122 | |
| SKBR3 | Growth Inhibition Assay | IC50=0.0075 ± 0.005 μM | 23816254 | ||
| BT474 | Growth Inhibition Assay | IC50=0.00323 ± 0.00075 μM | 23816254 | ||
| CAL-51 | Growth Inhibition Assay | IC50=1.89 μM | 24009064 | ||
| KPL-1 | Growth Inhibition Assay | IC50=1.89 μM | 24009064 | ||
| BT-549 | Growth Inhibition Assay | IC50=1.14 μM | 24009064 | ||
| MDA-MB-157 | Growth Inhibition Assay | IC50=1.12 μM | 24009064 | ||
| MDA-MB-231 | Growth Inhibition Assay | IC50=1.00 μM | 24009064 | ||
| UACC-732 | Growth Inhibition Assay | IC50=0.65 μM | 24009064 | ||
| HCC1143 | Growth Inhibition Assay | IC50=0.54 μM | 24009064 | ||
| HCC1937 | Growth Inhibition Assay | IC50=0.50 μM | 24009064 | ||
| HCC1395 | Growth Inhibition Assay | IC50=0.49 μM | 24009064 | ||
| HCC1806 | Growth Inhibition Assay | IC50=0.44 μM | 24009064 | ||
| MDA-MB-415 | Growth Inhibition Assay | IC50=0.42 μM | 24009064 | ||
| MCF-7 | Growth Inhibition Assay | IC50=0.41 μM | 24009064 | ||
| MDA-MB-436 | Growth Inhibition Assay | IC50=0.41 μM | 24009064 | ||
| CAMA-1 | Growth Inhibition Assay | IC50=0.37 μM | 24009064 | ||
| MDA-MB-468 | Growth Inhibition Assay | IC50=0.33 μM | 24009064 | ||
| MDA-MB-435 | Growth Inhibition Assay | IC50=0.33 μM | 24009064 | ||
| HCC38 | Growth Inhibition Assay | IC50=0.25 μM | 24009064 | ||
| MDA-MB-134 | Growth Inhibition Assay | IC50=0.17 μM | 24009064 | ||
| T-47D | Growth Inhibition Assay | IC50=0.16 μM | 24009064 | ||
| EFM-19 | Growth Inhibition Assay | IC50=0.11 μM | 24009064 | ||
| HCC1187 | Growth Inhibition Assay | IC50=0.10 μM | 24009064 | ||
| MDA-MB-453 | Growth Inhibition Assay | IC50=0.09 μM | 24009064 | ||
| BT-20 | Growth Inhibition Assay | IC50=0.07 μM | 24009064 | ||
| HCC70 | Growth Inhibition Assay | IC50=0.03 μM | 24009064 | ||
| ZR-75-1 | Growth Inhibition Assay | IC50=0.03 μM | 24009064 | ||
| SUM-190 | Growth Inhibition Assay | IC50=0.01 μM | 24009064 | ||
| SUM-225 | Growth Inhibition Assay | IC50=0.01 μM | 24009064 | ||
| UACC-893 | Growth Inhibition Assay | IC50<0.005 μM | 24009064 | ||
| UACC-812 | Growth Inhibition Assay | IC50<0.005 μM | 24009064 | ||
| SK-BR-3 | Growth Inhibition Assay | IC50<0.005 μM | 24009064 | ||
| MDA-MB-361 | Growth Inhibition Assay | IC50<0.005 μM | 24009064 | ||
| MDA-MB-175 | Growth Inhibition Assay | IC50<0.005 μM | 24009064 | ||
| HCC1954 | Growth Inhibition Assay | IC50<0.005 μM | 24009064 | ||
| HCC1569 | Growth Inhibition Assay | IC50<0.005 μM | 24009064 | ||
| EFM-192A | Growth Inhibition Assay | IC50<0.005 μM | 24009064 | ||
| BT-474 | Growth Inhibition Assay | IC50<0.005 μM | 24009064 | ||
| MDAMB453 | Growth Inhibition Assay | IC50=1.59 ± 0.179 μM | 23816254 | ||
| KB | Growth Inhibition Assay | IC50=4.13 ± 0.47 μM | 22491935 | ||
| KBv200 | Growth Inhibition Assay | IC50=6.03 ± 0.64 μM | 22491935 | ||
| MCF-7 | Growth Inhibition Assay | IC50=3.30 ± 0.41 μM | 22491935 | ||
| MCF-7/Adr | Growth Inhibition Assay | IC50= 2.88 ± 0.30 μM | 22491935 | ||
| MCF-7 | Growth Inhibition Assay | IC50=3.02 ± 0.34 μM | 22491935 | ||
| MCF-7/FLV1000 | Growth Inhibition Assay | IC50=7.09 ± 0.71 μM | 22491935 | ||
| HL60 | Growth Inhibition Assay | IC50=2.26 ± 0.23 μM | 22491935 | ||
| HL60/Adr | Growth Inhibition Assay | IC50=1.42 ± 0.15 μM | 22491935 | ||
| HEK293/pcDNA3.1 | Growth Inhibition Assay | IC50=5.29 ± 0.53 μM | 22491935 | ||
| HEK293/ABCB1 | Growth Inhibition Assay | IC50=6.91 ± 0.70 μM | 22491935 | ||
| L858R(EGFR) | Cell Viability Assay | decreases cell viability in time and dose dependent manner | 17311002 | ||
| L858R/T790M(EGFR) | Cell Viability Assay | decreases cell viability in time and dose dependent manner | 17311002 | ||
| G776insV_G/C | Cell Viability Assay | decreases cell viability in time and dose dependent manner | 17311002 | ||
| wild-type | Cell Viability Assay | decreases cell viability in time and dose dependent manner | 17311002 | ||
| A775insYVMA | Cell Viability Assay | decreases cell viability in time and dose dependent manner | 17311002 | ||
| G776insV_G/L | Cell Viability Assay | decreases cell viability in time and dose dependent manner | 17311002 | ||
| P780insGSP | Cell Viability Assay | decreases cell viability in time and dose dependent manner | 17311002 | ||
| NCI-H1781 | Growth Inhibition Assay | inhibits cell growth in time and dose dependent manner | 16818618 | ||
| HCC827 | Growth Inhibition Assay | inhibits cell growth in time and dose dependent manner | 16818618 | ||
| H3255 | Growth Inhibition Assay | inhibits cell growth in time and dose dependent manner | 16818618 | ||
| NCI-H1975 | Growth Inhibition Assay | inhibits cell growth in time and dose dependent manner | 16818618 | ||
| A549 | Growth Inhibition Assay | inhibits cell growth in time and dose dependent manner | 16818618 | ||
| 3T3 | Growth Inhibition Assay | IC50=700 ± 78 nM | 15173008 | ||
| 3T3/neu | Growth Inhibition Assay | IC50=3 ± 0.14 nM | 15173008 | ||
| SK-Br-3 | Growth Inhibition Assay | IC50=2 ± 0.18 nM | 15173008 | ||
| BT 474 | Growth Inhibition Assay | IC50=2 ± 0.06 nM | 15173008 | ||
| A431 | Growth Inhibition Assay | IC50=81 ± 9 nM | 15173008 | ||
| MDA-MB-435 | Growth Inhibition Assay | IC50=960 ± 165 nM | 15173008 | ||
| SW620 | Growth Inhibition Assay | IC50=690 ± 84 nM | 15173008 | ||
| SKBR3 | Function assay | Inhibition of human Her2 in SKBR3 cells, EC50 = 0.002 μM. | 18077425 | ||
| BT474 | Function assay | Inhibition of human Her2 in BT474 cells, EC50 = 0.002 μM. | 18077425 | ||
| A431 | Function assay | Inhibition of human Her2 in A431 cells, EC50 = 0.081 μM. | 18077425 | ||
| SW620 | Function assay | Inhibition of human Her2 in SW620 cells, EC50 = 0.69 μM. | 18077425 | ||
| BA/F3 | Cytotoxicity assay | Cytotoxicity against mouse BA/F3 cells expressing EGFR L858R mutant, IC50 = 0.0035 μM. | 19239229 | ||
| BA/F3 | Cytotoxicity assay | Cytotoxicity against mouse BA/F3 cells expressing EGFR L858R/T790M mutant, IC50 = 0.18 μM. | 19239229 | ||
| 點(diǎn)擊查看更多細(xì)胞系數(shù)據(jù) | |||||
生物活性
| 產(chǎn)品描述 | Neratinib是一種高度選擇性的HER2和EGFR抑制劑，在無細(xì)胞試驗(yàn)中IC50分別為59 nM 和 92 nM；微弱抑制KDR和Src，對(duì)Akt，CDK1/2/4，IKK-2，MK-2，PDK1，c-Raf和c-Met沒有顯著的抑制作用。Phase 3。 | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| 靶點(diǎn) |
|
| 體外研究(In Vitro) | ||||||
| 體外研究活性 | Neratinib微弱抑制酪氨酸激酶KDR 和Src，IC50分別為0.8 μM 和 1.4 μM,與 HER-2相比，活性分別弱14和24倍。Neratinib 作用于其他絲-蘇氨酸激酶如Akt, cyclin D1/cdk4, cyclin E/cdk2, cyclin B1/cdk1, IKK-2, MK-2, PDK1, c-Raf, 和Tpl-2，以及酪氨酸激酶c-Met沒有活性。Neratinib選擇性抑制轉(zhuǎn)染 HER-2 (3T3/neu)的3T3細(xì)胞增殖,也抑制兩種其他 HER-2-過表達(dá)的SK-Br-3和 BT474 cells細(xì)胞增殖，IC50為 2-3 nM,與未轉(zhuǎn)染的3T3細(xì)胞及 EGFR-和 HER-2陰性的MDA-MB-435 和 SW620細(xì)胞相比，效果高230倍以上。Neratinib也抑制EGFR-依賴的A431細(xì)胞增殖，IC50為81 nM。Neratinib 作用于BT474 細(xì)胞，降低HER-2受體自磷酸化， IC50 為5 nM,作用于A431細(xì)胞，降低EGF依賴的 EGFR磷酸化，IC50 為3 nM。Neratinib抑制 HER-2，導(dǎo)致下游MAPK和Akt通路受抑制，IC50為2 nM,比Trastuzumab更有效。Neratinib 作用于BT474細(xì)胞，抑制cyclin D1表達(dá)和 Rb-敏感性基因產(chǎn)物的磷酸化，IC50為9 nM,導(dǎo)致細(xì)胞周期停在G1-S期，最終降低細(xì)胞增殖。[1] | |||||
|---|---|---|---|---|---|---|
| 激酶實(shí)驗(yàn) | 使用時(shí)間-分辨熒光分析無細(xì)胞自磷酸化 | |||||
| Neratinib 在DMSO 中制備成10 mg/mL 儲(chǔ)液，然后在25 mM HEPES (pH 7.5; 0.002 ng/mL-20 μg/mL)中稀釋。純化重組的HER-2 COOH末端片段(第676-1255位氨基酸) 或EGFR COOH末端片段(第 645-1186位氨基酸)[在100 mM HEPES (pH 7.5) 和50% 甘油中稀釋] 與濃度不斷增高的Neratinib 在96-孔ELISA板上室溫下溫育15分鐘，孔中含4 mM HEPES (pH 7.5), 0.4 mM MnCl2, 20 μM 釩酸鈉，及 0.2 mM DTT 。加入 40 μM ATP 和20 mM MgCl2開始激酶反應(yīng)，然后在室溫下反應(yīng)1小時(shí)。沖洗實(shí)驗(yàn)板, 使用銪標(biāo)記的抗-磷酸化-酪氨酸抗體 (15 ng/每孔)檢測(cè)磷酸化。沖洗后，使用Victor2 熒光讀數(shù)儀 (激發(fā)波長(zhǎng)為340 nm,發(fā)射波長(zhǎng)為615 nm)測(cè)定信號(hào)。通過抑制曲線測(cè)定抑50%受體磷酸時(shí)的Neratinib 濃度 (IC50) 。 | ||||||
| 細(xì)胞實(shí)驗(yàn) | 細(xì)胞系 | 3T3, 3T3/neu, A431, BT474, SK-Br-3, MDA-MB-435, 和SW480 | ||||
| 濃度 | 溶于DMSO, 終濃度為0.5 ng/mL-5 μg/mL | |||||
| 孵育時(shí)間 | 2, 或6天 | |||||
| 方法 | 使用不同濃度Neratinib處理細(xì)胞 2, 或6 天。使用sulforhodamine B, 一種蛋白結(jié)合染料，測(cè)定細(xì)胞增殖。細(xì)胞與10% 三氯乙酸混合，然后使用水廣泛沖洗。使用 0.1% sulforhodamine B對(duì)細(xì)胞進(jìn)行染色，使用在5% 乙酸中清洗。蛋白-結(jié)合染10 mM Tris中,然后在450 nM處測(cè)定吸光度。通過抑制曲線測(cè)定抑制50% 細(xì)胞增殖時(shí)的Neratinib 濃度(IC50)。 | |||||
| 實(shí)驗(yàn)圖片 | 檢測(cè)方法 | 檢測(cè)指標(biāo) | 實(shí)驗(yàn)圖片 | PMID | ||
| Western blot |
| |||||