您当前所在的位置:首页 > 产品中心 > 产品详细信息
936091-26-8 分子结构
点击图片或这里关闭

N-tert-butyl-3-{[5-methyl-2-({4-[2-(pyrrolidin-1-yl)ethoxy]phenyl}amino)pyrimidin-4-yl]amino}benzene-1-sulfonamide

ChemBase编号:73194
分子式:C27H36N6O3S
平均质量:524.67814
单一同位素质量:524.25696004
SMILES和InChIs

SMILES:
c1(ccc(cc1)Nc1nc(c(cn1)C)Nc1cccc(c1)S(=O)(=O)NC(C)(C)C)OCCN1CCCC1
Canonical SMILES:
Cc1cnc(nc1Nc1cccc(c1)S(=O)(=O)NC(C)(C)C)Nc1ccc(cc1)OCCN1CCCC1
InChI:
InChI=1S/C27H36N6O3S/c1-20-19-28-26(30-21-10-12-23(13-11-21)36-17-16-33-14-5-6-15-33)31-25(20)29-22-8-7-9-24(18-22)37(34,35)32-27(2,3)4/h7-13,18-19,32H,5-6,14-17H2,1-4H3,(H2,28,29,30,31)
InChIKey:
JOOXLOJCABQBSG-UHFFFAOYSA-N

引用这个纪录

CBID:73194 http://www.chembase.cn/molecule-73194.html

Collapse All Expand All

名称和登记号

名称和登记号

名称 登记号
IUPAC标准名
N-tert-butyl-3-{[5-methyl-2-({4-[2-(pyrrolidin-1-yl)ethoxy]phenyl}amino)pyrimidin-4-yl]amino}benzene-1-sulfonamide
IUPAC传统名
N-tert-butyl-3-{[5-methyl-2-({4-[2-(pyrrolidin-1-yl)ethoxy]phenyl}amino)pyrimidin-4-yl]amino}benzenesulfonamide
别名
TG-101348
CAS号
936091-26-8
PubChem SID
162038114
PubChem CID
16722836

数据来源

数据来源

所有数据来源 商品来源 非商品来源
数据来源 数据ID 价格
Selleck Chemicals
S2736 external link 加入购物车 请登录
数据来源 数据ID
PubChem 16722836 external link

理论计算性质

理论计算性质

JChem
Acid pKa 10.211815  质子受体
质子供体 LogD (pH = 5.5) 1.5515648 
LogD (pH = 7.4) 3.23115  Log P 4.6356997 
摩尔折射率 147.8789 cm3 极化性 56.92408 Å3
极化表面积 108.48 Å2 可自由旋转的化学键 10 
里宾斯基五规则 false 

分子性质

分子性质

安全信息 药理学性质 产品相关信息 生物活性(PubChem)
保存条件
-20°C expand 查看数据来源
作用靶点
JAK expand 查看数据来源
成盐信息
Free Base expand 查看数据来源

详细说明

详细说明

Selleck Chemicals Selleck Chemicals
Selleck Chemicals -  S2736 external link
Biological Activity
Description TG-101348 (SAR302503) is a selective inhibitor of JAK2 with IC50 of 3 nM.
Targets JAK2
IC50 3 nM [1]
In Vitro TG-101348 also significantly inhibits JAK2 V617F, Flt3, and Ret with IC50 of 3 nM, 15 nM, and 48 nM, respectively. TG101348 has an IC50 ~300-fold higher for the closely related JAK3 and is a less potent inhibitor of the JAK1 and TYK2 family members. TG101348 inhibits proliferation of a human erythroblast leukemia (HEL) cell line that harbors the JAK2V617F mutation, as well as a murine pro-B cell line expressing human JAK2V617F (Ba/F3 JAK2V617F), with IC50 of 305 nM and 270 nM, respectively. TG-101348 also inhibits proliferation of parental Ba/F3 cells to a comparable level, with IC50 of ~420 nM. TG101348 treatment reduces STAT5 phosphorylation at concentrations that parallel the concentrations required to inhibit cell proliferation. TG101348 induces apoptosis in both HEL and Ba/F3 JAK2V617F cells in a dose-dependent manner. TG101348 does not show proapoptotic activity in control normal human dermal fibroblasts at concentrations up to 10 μM, and the antiproliferative IC50 against fibroblasts is >5 μM. [1] TG101348 treatment decreases GATA-1 expression, which is associated with erythroid-skewing of JAK2V617F+ progenitor differentiation, and inhibits STAT5 as well as GATA S310 phosphorylation. [2] TG101348 inhibits the proliferation of HMC-1.1 (KITV560G) cells, with somewhat lower potency than HMC-1.2 (KITD816V, KITV560G) cells, with IC50 of 740 nM and 407 nM, respectively. [3]
In Vivo TG101348 has potential for efficacious treatment of JAK2V617F-associated myeloproliferative diseases (MPD). In treated animals, there is a statistically significant reduction in hematocrit and leukocyte count, a dose-dependent reduction/elimination of extramedullary hematopoiesis, and, at least in some instances, evidence for attenuation of myelofibrosis, correlated with surrogate endpoints, including reduction/elimination of JAK2V617F disease burden, suppression of endogenous erythroid colony formation, and in vivo inhibition of JAK-STAT signal transduction. There are no apparent toxicities and no effect on T cell number. [1] Oral administration of TG101348 (120 mg/kg) significantly inhibits PV progenitor erythroid differentiation in vivo. [2]
Clinical Trials A Phase I/II study of TG-101348 in patients with primary or secondary myelofibrosis is ongoing.
Features
Combination Therapy
Description The combination of dasatinib and TG101348, when used individually at sub-IC50 concentrations, is synergistic for inhibition of HMC-1.2 cell proliferation. [3]
Protocol
Kinase Assay [1]
Cell-free Kinase Activity Assays IC50 values for TG101348 are determined commercially using the InVitrogen kinase profiling service for a 223 kinase screen that included JAK2 and JAK2V617F or Carna Biosciences for the screen of all Janus kinase family members including JAK1 and Tyk2. ATP concentration is set to approximately the Km value for each kinase.
Cell Assay [1]
Cell Lines EpoBa/F3 JAK2V617F, Ba/F3p210, HEL, and K562
Concentrations Dissolved in DMSO, final concentrations ~10 μM
Incubation Time 72 hours
Methods Approximately 2 × 103 cells are plated into microtiter-plate wells in 100 μL RPMI-1640 growth media with indicated concentrations of inhibitor. Following 72 hours incubation with TG101348, 50 μL of XTT dye are added to each well and incubated for 4 hours in a CO2 incubator. The colored formazan product is measured by spectrophotometry at 450 nm with correction at 650 nm. The concentration in which 50% of the effect (i.e., inhibition of proliferation) is observed (IC50) is determined using the GraphPad Prism 4.0 software. All experiments are performed in triplicate, and the results are normalized to growth of untreated cells. Induction of apoptosis of EpoBa/F3 JAK2V617F, Ba/F3p210, HEL, and K562 cells is determined by DNA fragmentation with DMSO and increasing concentrations of TG101348.
Animal Study [1]
Animal Models C57BL/6 mice injected intravenously with whole bone marrow expressing JAK2V617F
Formulation Dissolved in DMSO, and diluted in saline
Doses ~120 mg/kg
Administration Oral gavage twice daily (b.i.d.)
References
[1] Wernig G, et al. Cancer Cell, 2008, 13(4), 311-320.
[2] Geron I, et al. Cancer Cell, 2008, 13(4), 321-330.
[3] Lasho T, et al. Leukemia, 2010, 24(7), 1378-1380.

参考文献

参考文献

供应商提供 Google Scholar IconGoogle Scholar PubMed iconPubMed Google Books IconGoogle Books
正在搜索,请耐心等待...(如果遇到网页错误或者长时间没有结果,请刷新页面[F5])

专利

专利

PubChem iconPubChem Patent Google Patent Search IconGoogle Patent

互联网资源

互联网资源

百度图标百度 google iconGoogle