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| 活性类型 | 活性值-log(M) | 作用机制 | 期刊 | 参考文献(PubMed IDs) |
|---|
艾维替尼(AC0010), 表皮生长因子受体 erbB1 抑制剂
有货
为什么选择此级别
Moligand™ 级 ，适用于对基线干扰要求严格的色谱和分析工作流程。
储存与运输
-80℃储存。特低温运输 。请查阅批次 COA 获取详细规格。
质量文档
SDS、COA、产品数据表及规格说明书均可下载。可通过批号查询获取批次 COA。
文献证明
在色谱分析、有机合成和交叉偶联反应领域已被 0 篇同行评审文献引用。
概述
Avitinib (AC0010)是不可逆的EGFR抑制剂，对于突变型EGFR具有选择性，对EGFR L858R/T790M双突变体的IC50为0.18 nM，是对野生型EGFR效力的近43倍（IC50=7.68 nM for WT EGFR）。Avitinib具有抗肿瘤活性和耐受性毒性。
Information
Avitinib (AC0010) Avitinib (AC0010) is a pyrrolopyrimidine-based irreversible EGFR inhibitor that is mutation-selective with IC50 value of 0.18 nM against EGFR L858R/T790M double mutations, nearly 43-fold greater potency over wild-type EGFR (IC50 value, 7.68 nM). It has comparable anti-tumor activity and tolerated toxicity.
Targets
JAK3 (Cell-free assay); EGFR L858R/T790M (Cell-free assay); BTK (Cell-free assay) 0.09 nM; 0.18 nM; 0.4 nM
In vitro
AC0010 selectively inhibits EGFR active and T790M mutations with up to 298-fold increase in potency compared to wild-type EGFR. AC0010 selectively inhibited mutant EGFR phosphorylation with IC50 values of 7.3 nM and 2.8 nM in NCI-H1975 and NIH/3T3_TC32T8 cells, about 115- and 298-fold more sensitive than that of the inhibition of wild type EGFR in A431. Immunoblotting analysis confirmed that AC0010 potently inhibited EGFR-Tyr1068 phosphorylation in NCI-H1975 cells, and the selectivity ratio is at 65-fold for NCI-H1975 cells versus A431 cells. In addition to inhibition of EGFR-Tyr1068 phosphorylation, AC0010 inhibited phosphorylation of the downstream targets Akt and ERK1/2, two important kinases involved in cancer cell proliferation and survival, in NCI-H1975 and HCC827 cells. The selectivity of AC0010 was also assessed by testing its activity against a panel of 349 kinases. At a concentration of 1 μM, AC0010 exhibited greater than 80% inhibition in 33 out of 349 unique kinase assays (9.5%). Kinase targets with greater than 80% inhibition include JAK3, BTK and 5 TEC family members. However, at the cellular level, the kinase inhibitory potency is much less than with the enzymatic assay. Much weaker inhibition was seen in BTK and JAK3 cellular assays with IC50 values of 59 nM and 360 nM. When tested against a selected panel of 55 key molecular targets including receptors, ion channels and transporters, AC0010 (1 μM) inhibits 5 out of 55 targets over 50% inhibition of radioligand binding, including Adenosine A3, L-type calcium (Cav1.2) channel, dopamine transporter, 5-HT2A and 5-HT2B. However, in cell-based functional assays, no inhibition was detected for above 5 targets, implying that the risk of off-target binding of AC0010 is minimal at pharmacologically relevant concentrations.
In vivo
In a xenografte model, oral administration of AC0010 at daily dose of 500 mg/kg resulted in complete remission of tumors with EGFR active and T790M mutations for over 143 days with no weight loss. For PK analysis, following intravenous administration of 10 mg/kg of AC0010 in NCI-H1975 xenograft models, total body clearance and volume of distribution of AC0010 were estimated to be 5.91 L/h/kg and 14.76 L/kg, respectively. The elimination half-life (t1/2) of AC0010 was about 1.73 hour, indicating AC0010 is rapidly distributed into tissues including tumor tissues. Following oral administration of 12.5 mg/kg, 50 mg/kg and 200 mg/kg of AC0010 for 1 day or 8 consecutive days, AC0010 was absorbed with the Tmax of 1 to 2 hours, and bioavailability of 15.9-41.4%. AC0010 and its metabolites show no off-target effects and no skin lesion in animal models. Avitinib is well tolerated and efficacious in EGFR T790m(+) NSCLC patients. Its concentration in cerebrospinal fluid is low, and the penetrability of BBB is weak. But it still showed a good control of brain metastases (BM).
Cell Research(from reference)
Cell lines：NCI-H1975, HCC827, A431 and NIH/3T3_TC32T8 cells
Incubation Time：72 h
规格
别名
N-[3-[[2-[[3-氟-4-(4-甲基-1-哌嗪基)苯基]氨基]-7H-吡咯并[2,3-d]嘧啶-4-基]氧基]苯基]-2-丙烯酰胺
英文别名
1557267-42-1 | ACEA100610 | BCP16381 | Abivertinib | GTPL10044 | ABIVERTINIB [INN] | N-(3-((2-((3-Fluoro-4-(4-methylpiperazin-1-yl)phenyl)amino)-7H-pyrrolo(2,3-d)pyrimidin-4-yl)oxy)phenyl)prop-2-enamide | EX-ACEA0010 | N-[3-[[2-[[3-fluoro-4-(4-methyl-1-pi
规格或纯度
Moligand™, 10mM in DMSO
英文名称
Avitinib (AC0010)
生化机理
阿维替尼（AC0010）是一种基于吡咯并嘧啶的不可逆表皮生长因子受体抑制剂，具有突变选择性，对表皮生长因子受体 L858R/T790M 双突变的 IC50 值为 0.18 nM，比野生型表皮生长因子受体（IC50 值为 7.68 nM）的效力高出近 43 倍。它具有相当的抗肿瘤活性和可耐受的毒性。
储存条件
-80℃储存
运输条件
特低温运输
作用类型
抑制剂
作用机制
表皮生长因子受体 erbB1 抑制剂
名称和识别符
分子类型
小分子
IUPAC Name
N-[3-[[2-[3-fluoro-4-(4-methylpiperazin-1-yl)anilino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]oxy]phenyl]prop-2-enamide
INCHI
1S/C26H26FN7O2/c1-3-23(35)29-17-5-4-6-19(15-17)36-25-20-9-10-28-24(20)31-26(32-25)30-18-7-8-22(21(27)16-18)34-13-11-33(2)12-14-34/h3-10,15-16H,1,11-14H2,2H3,(H,29,35)(H2,28,30,31,32)
InChi Key
UOFYSRZSLXWIQB-UHFFFAOYSA-N
Smiles
CN1CCN(CC1)C2=C(C=C(C=C2)NC3=NC4=C(C=CN4)C(=N3)OC5=CC=CC(=C5)NC(=O)C=C)F
Isomeric SMILES
CN1CCN(CC1)C2=C(C=C(C=C2)NC3=NC4=C(C=CN4)C(=N3)OC5=CC=CC(=C5)NC(=O)C=C)F
分子量
487.53
Reaxy-Rn
26571715
Reaxys-RN link address
https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=26571715&ln=
技术文档
高级数据
系统学分类
分类树（Taxonomy Tree）
| 界（kingdom) | 有机化合物 |
|---|---|
| 超类（Superclass) | 有机杂环化合物 |
| 类（Class) | 二嗪烷 |
| 亚类（Subclass） | 哌嗪类 |
| 中间层级节点（Intermediate Tree Nodes） | 暂无 |
| 直接上位类(Direct Parent) | 苯基哌嗪类 |
| 其他上位类（Alternative Parents） | N-芳基哌嗪 二芳醚 吡咯并[2,3-d]嘧啶 苯胺类 苯胺和取代苯胺 苯氧基化合物 酚醚 二烷基芳胺 N-芳基酰胺 N-甲基哌嗪 氟苯类 氨基嘧啶及其衍生物 芳基氟化物 丙烯酸及其衍生物 吡咯类 杂芳族化合物 三烷基胺 仲羧酸酰胺 氨基酸及其衍生物 氮杂环化合物 羰基化合物 碳氢化合物衍生物 有机氧化物 有机氟化物 |
| 分子骨架（Molecular Framework) | 芳香族杂多环化合物 |
| 取代基（Substituents） | 丙烯酸或衍生物 - 氨基酸 - 氨基酸或其衍生物 - 氨基吡啶 - 苯胺类化合物 - 苯胺或取代苯胺 - 芳香族杂多环化合物 - 芳基氟化物 - 芳基卤化物 - 氮杂环 - 苯基化合物 - 羰基 - 羧酰胺基 - 羧酸衍生物 - 二烷基芳基胺 - 二芳基醚 - 乙醚 - 氟萘 - 卤苯 - 杂芳香族化合物 - 烃衍生物 - 单环苯基基团 - N-烷基哌嗪 - N-芳基酰胺 - N-芳基哌嗪 - N-甲基哌嗪 - 有机硝基化合物 - 有机氧化物 - 有机氧化合物 - 有机氟化物 - 有机卤化物 - 有机氮化合物 - 有机氧化合物 - 苯酚醚 - 苯氧基化合物 - 苯基哌嗪 - 嘧啶 - 吡咯 - 吡咯并[2,3-d]嘧啶 - 吡咯吡啶 - 醛基 - 三元脂肪胺 - 三级脂肪族/芳香族胺 - 三芳基胺 |
| 描述（Description） | 该化合物属于苯基哌嗪类有机化合物。这类化合物具有苯基哌嗪骨架，即哌嗪环与苯基相连的结构。 |
| 外部描述符（External Descriptors） | 暂无 |
三维结构
交互式化学结构模型
产品属性
| ALogP | 4.857 |
|---|---|
| hba_count | 4 |
| HBD Count | 3 |
| Rotatable Bond | 7 |
关联靶点（人）
EGFR
Tclin
表皮生长因子受体(Epidermal growth factor receptor)
(6 活性数据)
JAK3
Tclin
酪氨酸蛋白激酶JAK3(Tyrosine-protein kinase JAK3)
(1 活性数据)
BTK
Tclin
酪氨酸蛋白激酶 BTK(Tyrosine-protein kinase BTK)
(1 活性数据)
EGFR
Tclin
Epidermal growth factor receptor erbB1
(33727 活性数据)
ITK
Tclin
Tyrosine-protein kinase ITK/TSK
(3699 活性数据)
STAT3
Tchem
Signal transducer and activator of transcription 3
(3313 活性数据)
RPS6KB1
Tchem
Ribosomal protein S6 kinase 1
(4456 活性数据)
NCI-H1975
(4994 活性数据)
A549
(127892 活性数据)
NCI-H460
(60772 活性数据)
MAPK3
Tchem
Mitogen-activated protein kinase; ERK1/ERK2
(651 活性数据)
MAPK13
Tchem
MAP kinase p38
(1586 活性数据)
BEAS-2B
(690 活性数据)
HCC827
(1172 活性数据)
关联靶点（其它种属）
rep
Replicase polyprotein 1ab (378 活性数据)
SARS-CoV-2 (38078 活性数据)
作用机制
| 作用机制 | Action Type | target ID | Target Name | Target Type | Target Organism | Binding Site Name | 参考文献 |
|---|
化学和物理性质
DMSO(mg / mL) Max Solubility
97
DMSO(mM) Max Solubility
198.962115151888
Water(mg / mL) Max Solubility
＜1
分子量
487.500 g/mol
XLogP3
4.200
氢键供体数Hydrogen Bond Donor Count
3
氢键受体数Hydrogen Bond Acceptor Count
8
可旋转键计数Rotatable Bond Count
7
精确质量Exact Mass
487.213 Da
单同位素质量Monoisotopic Mass
487.213 Da
拓扑极表面积Topological Polar Surface Area
98.400 Ų
重原子数Heavy Atom Count
36
形式电荷Formal Charge
0
复杂度Complexity
752.000
同位素原子数Isotope Atom Count
0
定义的原子立体中心计数Defined Atom Stereocenter Count
0
未定义的原子立体中心计数Undefined Atom Stereocenter Count
0
定义的键立体中心计数Defined Bond Stereocenter Count
0
未定义的键立体中心计数Undefined Bond Stereocenter Count
0
所有立体化学键的总数The total count of all stereochemical bonds
0
共价键合单元计数Covalently-Bonded Unit Count
1
质检证书（CoA,COO,BSE/TSE 和分析图谱)
C of A & Other Certificates(BSE/TSE, COO):
输入批号以搜索分析图谱:
溶液计算器
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