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首页 / 抑制剂/激动剂 / 蛋白质酪氨酸激酶 / c-Kit / Dovitinib lactate/多韦替尼乳酸盐

Dovitinib lactate/多韦替尼乳酸盐 {[allProObj[0].p_purity_real_show]}

货号：A445850 同义名： TKI-258 lactate; CHIR-258 lactate

Dovitinib lactate是一种多靶点酪氨酸激酶抑制剂，能够抑制FLT3、c-Kit、VEGFR等靶标，具有抗癌潜力。

Dovitinib lactate/多韦替尼乳酸盐 化学结构 CAS号：692737-80-7
Dovitinib lactate/多韦替尼乳酸盐 化学结构
CAS号：692737-80-7
Dovitinib lactate/多韦替尼乳酸盐 3D分子结构
CAS号：692737-80-7
Dovitinib lactate/多韦替尼乳酸盐 化学结构 CAS号：692737-80-7
Dovitinib lactate/多韦替尼乳酸盐 3D分子结构 CAS号：692737-80-7
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Dovitinib lactate/多韦替尼乳酸盐 纯度/质量文件 产品仅供科研

货号：A445850 标准纯度： {[allProObj[0].p_purity_real_show]}
批次查询： 批次纯度:

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产品名称 c-Kit ↓ 其他靶点 纯度
Tyrphostin AG1296 +

c-Kit (Swiss 3T3), IC50: 1.8 μM

 		PDGFR 99%+
Masitinib +

Kit, IC50: 200 nM

 		99%+
Motesanib Diphosphate +++

Kit, IC50: 8 nM

 		97%
Ki8751 ++

c-Kit, IC50: 40 nM

 		99%
Tivozanib ++

c-Kit, IC50: 78 nM

 		99%+
Pazopanib +

c-Kit, IC50: 140 nM

 		99%
Sitravatinib +++

Kit, IC50: 6 nM

 		99%+
Pexidartinib +++

Kit, IC50: 10 nM

 		99%+
Lactate ++++

c-Kit, IC50: 2 nM

 		FLT3 85%
Amuvatinib +++

c-Kit (D816H), IC50: 10 nM

 		99%+
Imatinib Mesylate +

c-Kit, IC50: 100 nM

 		PDGFR 99%
AZD2932 +++

c-Kit, IC50: 9 nM

 		99%
Axitinib ++++

Kit, IC50: 1.7 nM

 		98%
Dovitinib ++++

c-Kit, IC50: 2 nM

 		FLT3 99%+
Sunitinib ✔ FLT3 98%
OSI-930 +

Kit, IC50: 80 nM

 		99%+
Telatinib ++++

c-Kit, IC50: 1 nM

 		99%+
Dasatinib monohydrate ++

c-Kit (wt), IC50: 79 nM

c-Kit (D816V), IC50: 37 nM

 		Src 98%
Dasatinib ++

c-Kit (wt), IC50: 79 nM

c-Kit (D816V), IC50: 37 nM

 		Src 98%
1. 鼠标悬停在“+”上可以显示相关IC50的具体数值。"+"越多，抑制作用越强。2. "✔"表示该化合物对相应的亚型有抑制作用，但抑制强度暂时没有相关数据。

Dovitinib lactate/多韦替尼乳酸盐 生物活性

描述 Fibroblast growth factors (FGFs) and FGF receptors (FGFRs) signaling network play essential roles to promote angiogenesis and tumor growth by binding to tyrosine kinase. Dovitinib (TKI258) is a small-molecule tyrosine kinase inhibitor targeting multiple RTKs, such as FGFRs. Dovitinib decreased the cell numbers in a dose-dependent manner in HCC1937 cells (IC50 = 13.8 μM), MCF-7 cells (IC50 = 12.7 μM), MDA-MB-231 cells (IC50 = 11.9 μM), MDA-MB-453 cells (IC50 = 9.7 μM), MDA-MB-468 cells (IC50 = 10.1 μM), and SK-BR-3 cells (IC50 = 11.7 μM). Dovitinib (0, 10, 15 μM; 24 h) induced the autophagy of various breast cancer cells through inhibiting STAT3/Mcl-1 axis in a dose-dependent manner. Treatment with 15 μM dovitinib induced about 15%, 40%, 25%, and 17% cell apoptosis at 24 h for MCF-7, MDA-MB-231, MDA-MB-468, and SK-BR-3 cells, respectively[3]. In mice bearing subcutaneous AN3CA, MFE296, SNGM, or HEC1A tumor xenografts, dovitinib (daily oral doses of 30 or 50 mg/kg) significantly delayed the growth of FGFR2-mutated endometrial cancer xenograft tumors. Of note, complete tumor regressions were observed in the majority of tumors at a dovitinib dose of 50 mg/kg in the SNGM xenograft model[4].

Dovitinib lactate/多韦替尼乳酸盐 细胞实验

Cell Line
Concentration Treated Time Description References
HeLa cells 2 μM Dovitinib activates GCN2 by increasing its affinity for ATP Nat Commun. 2023 Sep 8;14(1):5535.
HMVEC 0.04 μM 72 h To evaluate the inhibitory effect of Dovitinib on endothelial cell proliferation, results showed that Dovitinib significantly inhibited the proliferation of HMVEC cells at pharmacologically relevant concentrations. J Transl Med. 2012 Dec 10;10:245.
HUVEC 0.04 μM 72 h To evaluate the inhibitory effect of Dovitinib on endothelial cell proliferation, results showed that Dovitinib significantly inhibited the proliferation of HUVEC cells at pharmacologically relevant concentrations. J Transl Med. 2012 Dec 10;10:245.
SMMC7721 1.26 ± 0.15 μM 72 h To evaluate the inhibitory effect of Dovitinib on HCC cell proliferation, results showed that Dovitinib inhibited the proliferation of SMMC7721 cells at higher concentrations. J Transl Med. 2012 Dec 10;10:245.
MHCC-97H 0.87 ± 0.17 μM 72 h To evaluate the inhibitory effect of Dovitinib on HCC cell proliferation, results showed that Dovitinib inhibited the proliferation of MHCC-97H cells at higher concentrations. J Transl Med. 2012 Dec 10;10:245.
67NR cells 0.5 μM 1 hour To examine the effects of NVP-BEZ235 on signaling pathway activity in 67NR cells, results showed that NVP-BEZ235 significantly decreased levels of P-Akt and P-S6, but had no effect on P-Erk. Breast Cancer Res. 2013 Jan 23;15(1):R8.
4T1 cells 0.5 μM 1 hour To examine the effects of NVP-BEZ235 on signaling pathway activity in 4T1 and 67NR cells, results showed that NVP-BEZ235 significantly decreased levels of P-Akt and P-S6, but had no effect on P-Erk. Breast Cancer Res. 2013 Jan 23;15(1):R8.
U87MG cells 3, 4, 5 μM Dovitinib reduced tumor sphere formation, indicating inhibition of cancer stem cell self-renewal. Mol Oncol. 2017 Aug;11(8):1078-1098.
GB-10 patient cells 1, 2, 5 μM 24, 48, 72 h Dovitinib downregulated HMGA2 and pSTAT3, increased γH2AX levels indicating enhanced DNA damage. Mol Oncol. 2017 Aug;11(8):1078-1098.
U251 cells 1, 2, 5 μM 24, 48, 72 h Dovitinib downregulated HMGA2 and pSTAT3, increased γH2AX levels indicating enhanced DNA damage. Mol Oncol. 2017 Aug;11(8):1078-1098.
Rohon-Beard neurons 6 μM 48 h To evaluate the effect of Dovitinib on axon maintenance and cell survival of RB neurons, results showed significant axon loss and cell death. J Neurosci. 2024 Apr 17;44(16):e1600232024.

Dovitinib lactate/多韦替尼乳酸盐 动物实验

Species
Animal Model
Administration Dosage Frequency Description References
Nude mice Orthotopic HCC model 25 or 50 mg/kg Once daily for 14 days To evaluate the inhibitory effect of Dovitinib on HCC growth and metastasis, results showed that Dovitinib significantly inhibited tumor growth and lung metastasis. J Transl Med. 2012 Dec 10;10:245.
BALB/c mice 4T1 and 67NR mammary tumor models Oral 20 mg/kg Once daily for 14 days To evaluate the effects of dovitinib combined with NVP-BEZ235 on tumor growth and metastasis in 4T1 and 67NR models, results showed that the combination caused tumor stasis and significantly reduced lung metastasis. Breast Cancer Res. 2013 Jan 23;15(1):R8.
Mice MDA PCa 118b bone tumor model Oral gavage 40 or 60 mg/kg Daily treatment for 3 weeks or 7 days To assess the effect of Dovitinib on tumor volume and bone quality, results showed that Dovitinib significantly reduced tumor volume and improved bone quality. Sci Transl Med. 2014 Sep 3;6(252):252ra122
NOD/SCID mice Renal cell carcinoma tumorgraft model Oral gavage 30 mg/kg Once daily for ~28 days Dovitinib significantly inhibited RCC tumorgraft growth, showing greater activity than sunitinib and sirolimus, and was reasonably well tolerated. Sci Transl Med. 2012 Jun 6;4(137):137ra75
Nude mice LIV31 PDX model Oral gavage 30 mg/kg Daily for 63 days To evaluate the inhibitory effect of Dovitinib on the growth of LIV31 xenografts. Results showed that Dovitinib significantly inhibited tumor growth, decreased microvascular density, and induced apoptosis. Cancer Lett. 2016 Sep 28;380(1):163-73
Zebrafish Larval zebrafish Embryo medium 6 μM 48 hours To study the effect of Dovitinib on axon maintenance and cell survival of RB neurons in zebrafish, results showed significant axon loss and cell death. J Neurosci. 2024 Apr 17;44(16):e1600232024.

Dovitinib lactate/多韦替尼乳酸盐 临床研究

NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT01678105 Recurrent Adenoid Cystic Carci... 展开 >>noma of the Salivary Glands Metastatic Adenoid Cystic Carcinoma of the Salivary Glands Salivary Gland Cancers ACC 收起 << Phase 2 Completed - Canada, Ontario ... 展开 >> Tom Baker Cancer Centre Calgary, Ontario, Canada, T2N 4N2 Juravinski Cancer Centre Hamilton, Ontario, Canada, L8V 5C2 London Health Sciences Centre London, Ontario, Canada, N6A 4L6 Ottawa Hospital Regional Cancer Centre Ottawa, Ontario, Canada, K1H 8L6 收起 <<
NCT01223027 Metastatic Renal Cell Carcinom... 展开 >>a 收起 << Phase 3 Completed - -
NCT01496534 Solid Tumors ... 展开 >>Bladder Cancer 收起 << Phase 1 Terminated(toxicity of combina... 展开 >>tion of medications) 收起 << - United States, New York ... 展开 >> Icahn School of Medicine at Mount Sinai New York, New York, United States, 10029 收起 <<

Dovitinib lactate/多韦替尼乳酸盐 参考文献

[1]Huynh H, Chow PK, et al. Dovitinib demonstrates antitumor and antimetastatic activities in xenograft models of hepatocellular carcinoma. J Hepatol. 2012 Mar;56(3):595-601.

[2]Trudel S, Li ZH, et al. CHIR-258, a novel, multitargeted tyrosine kinase inhibitor for the potential treatment of t(4;14) multiple myeloma. Blood. 2005 Apr 1;105(7):2941-8.

[3]Chiu YH, et al. Dovitinib Triggers Apoptosis and Autophagic Cell Death by Targeting SHP-1/p-STAT3 Signaling in Human Breast Cancers. J Oncol. 2019 Aug 14;2019:2024648.

[4]Konecny GE, et al. Activity of the fibroblast growth factor receptor inhibitors dovitinib (TKI258) and NVP-BGJ398 in human endometrial cancer cells. Mol Cancer Ther. 2013 May;12(5):632-42.

Dovitinib lactate/多韦替尼乳酸盐 实验方案

计算器
存储液制备 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.07mL

0.41mL

0.21mL

10.36mL

2.07mL

1.04mL

20.72mL

4.14mL

2.07mL

Dovitinib lactate/多韦替尼乳酸盐 技术信息

CAS号692737-80-7
分子式C24H27FN6O4
分子量 482.51
SMILES Code O=C1NC2=C(C(F)=CC=C2)C(N)=C1C3=NC4=CC=C(N5CCN(C)CC5)C=C4N3.CC(O)C(O)=O
MDL No. MFCD16038905
别名 TKI-258 lactate; CHIR-258 lactate
运输蓝冰
InChI Key ZRHDKBOBHHFLBW-UHFFFAOYSA-N
Pubchem ID 135431668
存储条件

In solvent -20°C: 3-6个月 -80°C: 12个月

Pure form Sealed in dry,2-8°C
溶解方案

DMSO: 25 mg/mL(51.81 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO

Tags: Dovitinib | 692737-80-7 | CHIR-258 | TKI-258 | Tyrosine Kinase Inhibitor | Protein Tyrosine Kinase/RTK | FLT3 | c-Kit | FGFR | VEGFR | PDGFR | 仅供科研使用 | AmBeed-信号通路专用抑制剂 | Dovitinib lactate/多韦替尼乳酸盐 纯度/质量文件 | Dovitinib lactate/多韦替尼乳酸盐 亚型比较 | Dovitinib lactate/多韦替尼乳酸盐 生物活性 | Dovitinib lactate/多韦替尼乳酸盐 临床数据 | Dovitinib lactate/多韦替尼乳酸盐 参考文献 | Dovitinib lactate/多韦替尼乳酸盐 实验方案 | Dovitinib lactate/多韦替尼乳酸盐 技术信息

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