I2305641计算溶液所需的质量、体积或浓度。
| 活性类型 | 活性值-log(M) | 作用机制 | 期刊 | 参考文献(PubMed IDs) |
|---|
为什么选择此级别
提供 ≥96% 纯度，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
-20°C储存。超低温运输 。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
SAR125844是一种有效的、高选择性的Met (c-Met)激酶抑制剂，对野生型Met (c-Met)激酶具有纳摩尔级活性（IC50=4.2 nM），对H1094Y, Y1235D, M1250T, L1195V和D1228H突变体的IC50分别为0.22, 1.7, 6.5, 65和81 nM。
应用：
SAR125844 是一种有效的、高度选择性的、可逆的、ATP竞争性的 MET受体酪氨酸激酶 (RTK) 的抑制剂，其IC50 值为4.2 nM。能抑制细胞中MET的自磷酸化。
SAR125844 is a potent intravenously active and highly selective Met (c-Met) kinase inhibitor, displaying nanomolar activity against the wild-type kinase (IC50 value of 4.2 nmol/L) and H1094Y, Y1235D, M1250T, L1195V, and D1228H kinase domain mutants (IC50 values of 0.22, 1.7, 6.5, 65, and 81 nmol/L, respectively).
Application：
SAR125844, a potent and highly selective inhibitor of the MET receptor tyrosine kinase (RTK), for intravenous administration. (IC50 value of 4.2 nmol/L)
Information
SAR125844 SAR125844 is a potent intravenously active and highly selective Met (c-Met) kinase inhibitor, displaying nanomolar activity against the wild-type kinase (IC50 value of 4.2 nmol/L) and H1094Y, Y1235D, M1250T, L1195V, and D1228H kinase domain mutants (IC50 values of 0.22, 1.7, 6.5, 65, and 81 nmol/L, respectively).
Targets
MET H1094Y (Cell-free assay); MET Y1235D (Cell-free assay); WT MET (Cell-free assay); MET M1250T (Cell-free assay); TRKA/NTRK1 (Cell-free assay) 31629,0.22 nM; 1.7 nM; 4.2 nM; 6.5 nM; 39 nM
In vitro
SAR125844 is an ATP-competitive and reversible inhibitor. The biochemical selectivity of SAR125844 is documented in a panel of 275 human kinases and against tubulin. SAR125844 is moderately active on RON, a close structural homolog of MET, with IC50 value of approximately 740 nmol/L, suggesting that SAR125844 is highly (>100-fold) selective for the MET kinase over RON. Minimal inhibitory activity is identified on 5 additional kinases with IC50 values below 300 nmol/L, including TRKA/NTRK1 (39 nmol/L), TRKB/NTRK2 (280 nmol/L), PDGFRα-V561D (55 nmol/L), AXL (87 nmol/L), and MER (105 nmol/L). Biochemical activities on Aurora A and Aurora B are detected with IC50 values of 320 and 820 nmol/L, respectively, but these activities do not translate into cellular activity as demonstrated by the lack of antiproliferative activity in tumor cell lines without MET gene amplification. No activity on tubulin is detected up to 25 μmol/L of SAR125844. SAR125844 inhibits MET autophosphorylation in cell-based assays in the nanomolar range, and promotes low nanomolar proapoptotic and antiproliferative activities selectively in cell lines with MET gene amplification or pathway addiction.
In vivo
In PK studies in mice, the oral bioavailability of SAR125844 is low (∼2%), in line with its moderate Caco-2 permeability. In female SCID mice bearing xenograft tumors based on the MET-amplified Hs 746T human gastric tumor cell line, a single intravenous administration at 20 mg/kg is performed. plasma exposure of SAR125844 (area under the curve (AUC)) is 6190 h·ng/mL, the clearance moderate (CL = 3.1 L/h/kg), and the volume of distribution is large (Vss = 4.2 L/kg). A rapid and sustained uptake of SAR125844 in tumor tissue is observed, associated with a slower decrease of concentration from tumor tissue compared to the plasma concentration. The clearances of SAR125844 in mice, rats, and dogs are moderate. The plasma terminal elimination half-life (t1/2) is moderate (rats and dogs) to long (mice). The volume of distribution at steady state is moderate in dogs and large in rodents. In two MET-amplified human gastric tumor xenograft models, SNU-5 and Hs 746T, intravenous treatment with SAR125844 leads to potent, dose- and time-dependent inhibition of the MET kinase and to significant impact on downstream PI3K/AKT and RAS/MAPK pathways. Daily or every-2-days intravenous treatment of SAR125844 promots a dose-dependent tumor regression in MET-amplified human gastric cancer models at tolerated doses without treatment-related body weight loss.
Cell Research(from reference)
Cell lines：MKN-45, Hs 746T, and SNU-5 cells
Incubation Time：1 hour
规格
英文别名
DTXSID901031348 | 1116743-46-4 | CALCIUM ACETATE, ANHYDROUS (EP IMPURITY) | SAR125844 | SAR-125844 | 1-(6-{[6-(4-fluorophenyl)[1,2,4]triazolo[4,3-b]pyridazin-3-yl]sulphanyl}-1,3-benzothiazol-2-yl)-3-(2-morpholin-4-ylethyl)urea | HY-16446 | 1-(6-((6-(4-flu
规格或纯度
≥96%
英文名称
SAR125844
生化机理
SAR125844 是一种具有强效静脉注射活性和高选择性的 Met（c-Met）激酶抑制剂，对野生型激酶（IC50 值为 4.2 nmol/L）以及 H1094Y、Y1235D、M1250T、L1195V 和 D1228H 激酶域突变体（IC50 值分别为 0.22、1.7、6.5、65 和 81 nmol/L）具有纳摩尔级的活性。
储存条件
-20°C储存
运输条件
超低温运输
纯度
≥96%
名称和识别符
PubChem SID
分子类型
小分子
IUPAC Name
1-[6-[[6-(4-fluorophenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl]sulfanyl]-1,3-benzothiazol-2-yl]-3-(2-morpholin-4-ylethyl)urea
INCHI
1S/C25H23FN8O2S2/c26-17-3-1-16(2-4-17)19-7-8-22-30-31-25(34(22)32-19)37-18-5-6-20-21(15-18)38-24(28-20)29-23(35)27-9-10-33-11-13-36-14-12-33/h1-8,15H,9-14H2,(H2,27,28,29,35)
InChi Key
ODIUNTQOXRXOIV-UHFFFAOYSA-N
Smiles
C1COCCN1CCNC(=O)NC2=NC3=C(S2)C=C(C=C3)SC4=NN=C5N4N=C(C=C5)C6=CC=C(C=C6)F
Isomeric SMILES
C1COCCN1CCNC(=O)NC2=NC3=C(S2)C=C(C=C3)SC4=NN=C5N4N=C(C=C5)C6=CC=C(C=C6)F
PubChem CID
分子量
550.63
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) | 二嗪类 |
| 亚类（Subclass） | 哒嗪及其衍生物 |
| 中间层级节点（Intermediate Tree Nodes） | 暂无 |
| 直接上位类(Direct Parent) | 苯哒嗪类 |
| 其他上位类（Alternative Parents） | 二芳基硫醚 苯并噻唑 三唑并哒嗪类 苯硫酚醚 氟苯类 芳基氟化物 吗啉 噻唑类 杂芳族化合物 三唑类 尿素 三烷基胺 亚磺酰基化合物 氧环化合物 二烷基醚 氮杂环化合物 有机氟化物 有机氧化物 碳氢化合物衍生物 羰基化合物 |
| 分子骨架（Molecular Framework) | 芳香族杂多环化合物 |
| 取代基（Substituents） | 1,2,4-三唑 - 1,3-苯并噻唑 - 氨基酸 - 芳香族杂多环化合物 - 芳基氟化物 - 芳基卤化物 - 芳基硫醚 - 氮杂环 - 吡唑 - 苯基化合物 - 羰基 - 二烷基醚 - 二芳基硫醚 - 乙醚 - 氟萘 - 卤苯 - 杂芳香族化合物 - 烃衍生物 - 单环苯基基团 - Morpholine - 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 - 有机硫化合物 - 氧杂环 - 氧杂吡嗪烷 - 苯基吡嗪 - 硫酰基化合物 - 三元脂肪胺 - 三芳基胺 - 噻唑 - 硫醚 - 硫酚醚 - 三唑吡嗪 - 脲 |
| 描述（Description） | 该化合物属于苯基哒嗪类有机化合物。这类化合物具有哒嗪环结构，其上被苯基取代。 |
| 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 | 4.518 |
|---|---|
| HBD Count | 2 |
| Rotatable Bond | 7 |
关联靶点（人）
MET
Tclin
肝细胞生长因子受体(Hepatocyte growth factor receptor)
(4 活性数据)
MET
Tclin
Hepatocyte growth factor receptor
(10718 活性数据)
CYP3A4
Tclin
Cytochrome P450 3A4
(53859 活性数据)
关联靶点（其它种属）
Mus musculus (284745 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
溶解性
Solubility (25°C) In vitro DMSO: 11 mg/mL (19.97 mM); Water: ˂1 mg/mL Ethanol: ˂1 mg/mL；DMSO:45 mg/mL (81.72 mM)
DMSO(mg / mL) Max Solubility
11
DMSO(mM) Max Solubility
19.9771171203894
Water(mg / mL) Max Solubility
＜1
分子量
550.600 g/mol
XLogP3
3.400
氢键供体数Hydrogen Bond Donor Count
2
氢键受体数Hydrogen Bond Acceptor Count
10
可旋转键计数Rotatable Bond Count
7
精确质量Exact Mass
550.137 Da
单同位素质量Monoisotopic Mass
550.137 Da
拓扑极表面积Topological Polar Surface Area
163.000 Ų
重原子数Heavy Atom Count
38
形式电荷Formal Charge
0
复杂度Complexity
790.000
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)
溶液计算器
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