产品号 #73442_C
酪氨酸激酶抑制剂；抑制KDR、PDGFR、KIT、RET、FLT-3、ABL、ALK
总览
SU5416是一种酪氨酸激酶抑制剂，其最广为人知的特性是作为激酶插入域（KDR/VEGFR2/FLK1）的ATP竞争性抑制剂。除了抑制KDR（IC₅₀=1 μM）外，SU5416还抑制PDGFR（IC₅₀=20 μM）、KIT（IC₅₀=30 nM）、RET（IC₅₀=170 nM）、FLT-3（IC₅₀=160 nM）、ABL（IC₅₀=11 μM）和ALK（IC₅₀=1.2 μM）。 SU5416不抑制EGFR或FGFR酪氨酸激酶（IC₅₀> 100 μM；Fong et al.; Litz; Mologni et al.）。
癌症研究
·阻止血管生成，从而抑制多种癌症的肿瘤生长、催化和血管化（Litz; Fong et al.）。
·抑制RET介导的NIH-3T3小鼠成纤维细胞和Ba/F3小鼠前B细胞转化（Mologni et al.）。
疾病建模
·在缺氧条件下，可引起SuHx大鼠模型中的肺动脉高压（de Raaf et al.; Mizuno et al.）。
免疫学
·抑制TGFβ1活化并延缓大鼠伤口愈合（Haroon et al.）。
细胞类型
癌细胞及细胞系
种属
人，小鼠，非人灵长类，其它细胞系，大鼠
研究领域
血管生成细胞研究，癌症，疾病建模，免疫
CAS 编号
204005-46-9
化学式
C₁₅H₁₄N₂O
纯度
≥98%
通路
酪氨酸激酶
靶点
ABL，ALK，FLT-3，KDR，KIT，PDGFR，RET
Protocols and Documentation
Find supporting information and directions for use in the Product Information Sheet or explore additional protocols below.
Resources and Publications
Educational Materials (3)
Publications (5)
SuHx rat model: partly reversible pulmonary hypertension and progressive intima obstruction. The European respiratory journal 2014
Abstract
The SU5416 combined with hypoxia (SuHx) rat model features angio-obliterative pulmonary hypertension resembling human pulmonary arterial hypertension. Despite increasing use of this model, a comprehensive haemodynamic characterisation in conscious rats has not been reported. We used telemetry to characterise haemodynamic responses in SuHx rats and associated these with serial histology. Right ventricular systolic pressure (RVSP) increased to a mean±sd of 106±7 mmHg in response to SuHx and decreased but remained elevated at 72±8 mmHg upon return to normoxia. Hypoxia-only exposed rats showed a similar initial increase in RVSP, a lower maximum RVSP and near-normalisation of RVSP during subsequent normoxia. Progressive vascular remodelling consisted of a four-fold increase in intima thickness, while only minimal changes in media thickness were found. The circadian range in RVSP provided an accurate longitudinal estimate of vascular remodelling. In conclusion, in SuHx rats, re-exposure to normoxia leads to a partial decrease in pulmonary artery pressure, with persisting hypertension and pulmonary vascular remodelling characterised by progressive intima obstruction.
Severe pulmonary arterial hypertension induced by SU5416 and ovalbumin immunization. American journal of respiratory cell and molecular biology 2012
Abstract
The combination of chronic hypoxia and treatment of rats with the vascular endothelial growth factor (VEGF) receptor blocker, SU5416, induces pulmonary angio-obliteration, resulting in severe pulmonary arterial hypertension (PAH). Inflammation is thought to contribute to the pathology of PAH. Allergic inflammation caused by ovalbumin (OVA) immunization causes muscularization of pulmonary arteries, but not severe PAH. Whether disturbance of the immune system and allergic inflammation in the setting of lung endothelial cell apoptosis causes PAH is unknown. We investigated the effects of OVA-allergic inflammation on the development of PAH initiated by VEGF blockade-induced lung endothelial cell apoptosis. OVA-immunized rats were treated with SU5416 to induce pulmonary vascular endothelial cell apoptosis. The combination of OVA and SU5416 treatment resulted in severe angio-obilterative PAH, accompanied by increased IL-6 expression in the lungs. c-Kit(+) and Sca-1(+) cells were found in and around the lung vascular lesions. Pan-caspase inhibiton, dexamethasone treatment, and depletion of B-lymphocytes using an anti-CD20 antibody suppressed this remodeling. OVA immunization also increased lung tissue hypoxia-induced factor-1α and VEGF expression. Our results also suggest that the increased expression of hypoxia-induced factor-1α and IL-6 induced by the allergic lung inflammation may be a component of the pathogenesis of PAH.
Inhibition of RET tyrosine kinase by SU5416. Journal of molecular endocrinology 2006
Abstract
Thyroid neoplasia is frequently associated with rearranged during transfection (RET) proto-oncogene mutations that cause hyperactivation of RET kinase activity. Selective inhibition of RET-mediated signaling should lead to an efficacious therapy. SU5416 is a potent inhibitor of vascular endothelial cell growth factor receptor, c-Kit, and FLT-3 receptor tyrosine kinases presently used in clinical trials. We found that SU5416 inhibits RET with similar potency, both in cell-free assays and in cells, thus causing proliferation arrest in oncogenic RET-transfected cells and in papillary thyroid carcinoma (PTC) cells expressing the RET/PTC1 oncogene, but not in RET-negative control cells. SU5416 inhibited RET-mediated signaling through the extracellular signal regulated kinase (ERK) and JNK pathways. In addition, we show that a naturally occurring MEN2 mutation at codon 804 confers resistance to SU5416, but not to the related compound SU4984. We provide a possible explanation to these results by using molecular docking. Finally, SU5416 was also assessed against an array of 52 tyrosine and serine/threonine kinases.
更多信息
| Species | Human, Mouse, Non-Human Primate, Other, Rat |
|---|---|
| Cas Number | 204005-46-9 |
| Chemical Formula | C₁₅H₁₄N₂O |
| Purity | ≥ 98% |
| Target | ABL, ALK, FLT-3, KDR, KIT, PDGFR, RET |
| Pathway | Tyrosine Kinase |
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