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341031-54-7 分子结构
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(2S)-2-hydroxybutanedioic acid; N-[2-(diethylamino)ethyl]-5-{[(3Z)-5-fluoro-2-oxo-2,3-dihydro-1H-indol-3-ylidene]methyl}-2,4-dimethyl-1H-pyrrole-3-carboxamide

ChemBase编号:72476
分子式:C26H33FN4O7
平均质量:532.5612232
单一同位素质量:532.23332764
SMILES和InChIs

SMILES:
c1(ccc2c(c1)/C(=C/c1[nH]c(c(c1C)C(=O)NCCN(CC)CC)C)/C(=O)N2)F.C(=O)(C[C@@H](C(=O)O)O)O
Canonical SMILES:
OC(=O)C[C@@H](C(=O)O)O.CCN(CCNC(=O)c1c(C)[nH]c(c1C)/C=C/1\C(=O)Nc2c1cc(F)cc2)CC
InChI:
InChI=1S/C22H27FN4O2.C4H6O5/c1-5-27(6-2)10-9-24-22(29)20-13(3)19(25-14(20)4)12-17-16-11-15(23)7-8-18(16)26-21(17)28;5-2(4(8)9)1-3(6)7/h7-8,11-12,25H,5-6,9-10H2,1-4H3,(H,24,29)(H,26,28);2,5H,1H2,(H,6,7)(H,8,9)/b17-12-;/t;2-/m.0/s1
InChIKey:
LBWFXVZLPYTWQI-IPOVEDGCSA-N

引用这个纪录

CBID:72476 http://www.chembase.cn/molecule-72476.html

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名称和登记号

名称和登记号

名称 登记号
IUPAC标准名
(2S)-2-hydroxybutanedioic acid; N-[2-(diethylamino)ethyl]-5-{[(3Z)-5-fluoro-2-oxo-2,3-dihydro-1H-indol-3-ylidene]methyl}-2,4-dimethyl-1H-pyrrole-3-carboxamide
(2S)-2-hydroxybutanedioic acid; N-[2-(diethylamino)ethyl]-5-[(5-fluoro-2-oxo-2,3-dihydro-1H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide
IUPAC传统名
(-)-malic acid; sunitinib
别名
Sutent
SU-11248
Sunitinib Malate
N-[2-(Diethylamino)ethyl]-5-[(Z)-(5-fluoro-1,2-dihydro-2-oxo-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide (2S)-2-hydroxybutanedioic acid (1:1) salt
SU 011248
SU 11248
SU112248
Sunitinib malate
N-[2-(Diethylamino)ethyl]-5-[(Z)-(5-fluoro-1,2-dihydro-2-oxo-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide Malate
CAS号
341031-54-7
MDL号
MFCD08282795
PubChem SID
162037401
PubChem CID
6456015

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
PubChem 6456015 external link

理论计算性质

理论计算性质

JChem
Acid pKa 11.462899  质子受体
质子供体 LogD (pH = 5.5) -0.2940416 
LogD (pH = 7.4) 1.2792807  Log P 2.9273767 
摩尔折射率 116.2663 cm3 极化性 42.123272 Å3
极化表面积 77.23 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

理化性质 安全信息 药理学性质 产品相关信息 生物活性(PubChem)
溶解度
DMSO expand 查看数据来源
DMSO: >10 mg/mL expand 查看数据来源
Methanol expand 查看数据来源
外观
powder expand 查看数据来源
Yellow Solid expand 查看数据来源
熔点
189-191°C expand 查看数据来源
保存条件
-20°C expand 查看数据来源
-20°C Freezer expand 查看数据来源
欧盟危险性物质标志
有毒(Toxic) 有毒(Toxic) (T) expand 查看数据来源
MSDS下载
下载链接 expand 查看数据来源
下载链接 expand 查看数据来源
德国WGK号
2 expand 查看数据来源
危险公开号
61-2-48/25 expand 查看数据来源
安全公开号
53-22-36/37 expand 查看数据来源
GHS危险品标识
GHS08 expand 查看数据来源
GHS警示词
Danger expand 查看数据来源
GHS危险声明
H360-H372 expand 查看数据来源
GHS警示性声明
P201-P308 + P313 expand 查看数据来源
保存温度
room temp expand 查看数据来源
作用靶点
c-Kit expand 查看数据来源
Flt expand 查看数据来源
PDGFR expand 查看数据来源
VEGFR expand 查看数据来源
纯度
≥98% (HPLC) expand 查看数据来源
成盐信息
Malate expand 查看数据来源
质检报告
下载链接 expand 查看数据来源
Empirical Formula (Hill Notation)
C22H27FN4O2 · C4H6O5 expand 查看数据来源

详细说明

详细说明

Selleck Chemicals Selleck Chemicals Sigma Aldrich Sigma Aldrich TRC TRC
Selleck Chemicals -  S1042 external link
Research Area
Description Cancer
Biological Activity
Description Sunitinib Malate (Sutent, SU11248) is a potent RTK inhibitor targeting VEGFR2 (Flk-1) and PDGFRβ with IC50 of 80 nM and 2 nM, respectively.
Targets VEGFR2 (Flk-1) PDGFRβ
IC50 80 nM 2 nM [1]
In Vitro Sunitinib also potently inhibits Kit and FLT-3. [1] Sunitinib is a potent ATP-competitive inhibitor of VEGFR2 (Flk1) and PDGFRβ with Ki of 9 nM and 8 nM, respectively, displaying >10-fold higher selectivity for VEGFR2 and PDGFR than FGFR-1, EGFR, Cdk2, Met, IGFR-1, Abl, and src. In serum-starved NIH-3T3 cells expressing VEGFR2 or PDGFRβ, Sunitinib inhibits VEGF-dependent VEGFR2 phosphorylation and PDGF-dependent PDGFRβ phosphorylation with IC50 of 10 nM and 10 nM, respectively. Sunitinib inhibits VEGF-induced proliferation of serum-starved HUVECs with IC50 of 40 nM, and inhibits PDGF-induced proliferation of NIH-3T3 cells overexpressing PDGFRβ or PDGFRα with IC50 of 39 nM and 69 nM, respectively. [2] Sunitinib inhibits phosphorylation of wild-type FLT3, FLT3-ITD, and FLT3-Asp835 with IC50 of 250 nM, 50 nM, and 30 nM, respectively. Sunitinib inhibits the proliferation of MV4;11 and OC1-AML5 cells with IC50 of 8 nM and 14 nM, respectively, and induces apoptosis in a dose-dependent manner. [3]
In Vivo Consistent with the substantial and selective inhibition of VEGFR2 or PDGFR phosphorylation and signaling in vivo, Sunitinib (20-80 mg/kg/day) exhibits broad and potent dose-dependent anti-tumor activity against a variety of tumor xenograft models including HT-29, A431, Colo205, H-460, SF763T, C6, A375, or MDA-MB-435. Sunitinib dosing at 80 mg/kg/day for 21 days leads to complete tumor regression in six of eight mice, without tumor re-growing during a 110-day observation period after the end of treatment. Second round of treatment with Sunitinib remains efficacious against tumors that are not fully regressed during the first round of treatment. Sunitinib treatment results in significant decrease in tumor MVD, with ~40% reduction in SF763T glioma tumors. SU11248 treatment results in a complete inhibition of additional tumor growth of luciferase-expressing PC-3M xenografts, despite no reduction in tumor size. [2] Sunitinib treatment (20 mg/kg/day) dramatically suppresses the growth subcutaneous MV4;11 (FLT3-ITD) xenografts and prolongs survival in the FLT3-ITD bone marrow engraftment model. [3]
Clinical Trials A Phase I/II study of Sunitinib in young patients with advanced gastrointestinal stromal tumor is currently ongoing.
Features
Combination Therapy
Description Sunitinib in combination with docetaxel, 5-FU, or doxorubicin significantly enhances growth inhibition of MX-1 Tumors. Sunitinib enhances docetaxel-induced tumor growth delay in 435/HAL-Luc breast carcinoma growth in the bone. [4] Sunitinib in combination with the conventional anticancer agent cytarabine or daunorubicin displays synergistic inhibitory effect on the proliferation and survival of FLT3 ITD-positive MV4-11 and MOLM14 leukemic cells. [5] Rapamycin analogue RAD001 (100 nM) enhances the ability of Sunitinib (2-4 nM) to inhibit the proliferation of MV4-11, EOL-1, Kasumi, KU812, K562, and PALL-2 cells and down-regulate levels of mammalian target of rapamycin effectors p70 S6 kinase and eukaryotic initiation factor 4E–binding protein. [6] A Phase I/II study of Sunitinib plus paclitaxel and carboplatin as neoadjuvant treatment for locally advanced breast cancer is currently ongoing.
Protocol
Kinase Assay [1]
Biochemical Tyrosine Kinase Assays IC50 values for Sunitinib against VEGFR2 (Flk-1) and PDGFRβ are determined using glutathione S-transferasefusion proteins containing the complete cytoplasmic domain of the RTK. Biochemical tyrosine kinase assays to quantitate the trans-phosphorylation activity of VEGFR2 (Flk-1) and PDGFRβ are performed in 96-well microtiter plates precoated (20 μg/well in PBS; incubated overnight at 4 °C) with the peptide substrate poly-Glu,Tyr (4:1). Excess protein binding sites are blocked with the addition of 1-5% (w/v) BSA in PBS. Purified GST-fusion proteins are produced in baculovirus-infected insect cells. GST-VEGFR2 and GST-PDGFRβ are then added to the microtiter wells in 2 × concentration kinase dilution buffer consisting of 100 mM HEPES, 50 mM NaCl, 40 μM NaVO4, and 0.02% (w/v) BSA. The final enzyme concentration for GST-VEGFR2 or GST-PDGFRβ is 50 ng/mL. Twenty-five μL of diluted Sunitinib are subsequently added to each reaction well to produce a range of inhibitor concentrations appropriate for each enzyme. The kinase reaction is initiated by the addition of different concentrations of ATP in a solution of MnCl2 so that the final ATP concentrations spanned the Km for the enzyme, and the final concentration of MnCl2 is 10 mM. The plates are incubated for 5-15 minutes at room temperature before stopping the reaction with the addition of EDTA. The plates are then washed three times with TBST. Rabbit polyclonal antiphosphotyrosine antisera are added to the wells at a 1:10,000 dilution in TBST containing 0.5% (w/v) BSA, 0.025% (w/v) nonfat dry milk, and 100 μM NaVO4 and incubated for 1 hour at 37 °C. The plates are then washed three times with TBST, followed by the addition of goat antirabbit antisera conjugated with horseradish peroxidase (1:10,000 dilution in TBST). The plates are incubated for 1 hour at 37 °C and then washed three times with TBST. The amount of phosphotyrosine in each well is quantitated after the addition of 2,2′-azino-di-[3-ethylbenzthiazoline sulfonate] as substrate.
Cell Assay [3]
Cell Lines RS4;11, MV4;11, and OC1-AML5
Concentrations Dissolved in DMSO, final concentrations ~10 μM
Incubation Time 24 and 48 hours
Methods Cells are starved overnight in medium containing 0.1% FBS prior to addition of Sunitinib and FL (50 ng/mL; FLT3-WT cells only). Proliferation is measured after 48 hours of culture using the Alamar Blue assay or trypan blue cell viability assays. Apoptosis is measured 24 hours after Sunitinib addition by Western blotting to detect cleavage of poly (ADP-ribose) polymerase (PARP) or levels of caspase-3.
Animal Study [2]
Animal Models Female nu/nu mice implanted s.c. with HT-29, A431, Colo205, H-460, SF763T, C6, A375, or MDA-MB-435, and male nu/nu mice bearing luciferase-expressing PC-3M tumors
Formulation Formulated as a carboxymethyl cellulose suspension or as a citrate buffered (pH 3.5) solution
Doses ~80 mg/kg
Administration Orally once daily
References
[1] Sun L, et al. J Med Chem, 2003, 46(7), 1116-1119.
[2] Mendel DB, et al. Clin Cancer Res, 2003, 9(1), 327-337.
[3] O'Farrell AM, et al. Blood, 2003, 101(9), 3597-3605.
[4] Abrams TJ, et al. Mol Cancer Ther, 2003, 2(10), 1011-1021.
[5] Yee KW, et al. Blood, 2004, 104(13), 4202-4209.
[6] Ikezoe T, et al. Mol Cancer Ther, 2006, 5(10), 2522-2530.
Sigma Aldrich -  PZ0012 external link
Biochem/physiol Actions
Sunitinib malate is a receptor tyrosine kinase inhibitor, which targets VEGF-R1, VEGF-R2, VEGF-R3, PDGF-Rα, PDGF-Rβ, KIT, FLT3, CSF-1R, and RET. Sunitinib malate is an anticancer drug.
Legal Information
Sold for research purposes under agreement from Pfizer Inc.
Toronto Research Chemicals -  S820000 external link
A multi-kinase inhibitor targeting several receptor tyrosine kinases (RTK). Antineoplastic.

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