更新于：2024-11-01

SSTR2 x Tubulin

更新于：2024-11-01

基本信息

关联

项与 SSTR2 x Tubulin 相关的药物

PEN-221

靶点

SSTR2 x Tubulin

作用机制

SSTR2调节剂 [+1]

在研机构-

原研机构

Tarveda Therapeutics, Inc.

在研适应症-

非在研适应症

晚期癌症 [+3]

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

项与 SSTR2 x Tubulin 相关的临床试验

NCT02936323 / Completed临床1/2期

A Phase 1/2a, Open-label Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of PEN-221 in Patients With Somatostatin Receptor 2 Expressing Advanced Cancers, Including Gastroenteropancreatic or Lung or Thymus or Other Neuroendocrine Tumors or Small Cell Lung Cancer or Large Cell Neuroendocrine Carcinoma of the Lung

Protocol PEN-221-001 is an open-label, multicenter Phase 1/2a study evaluating PEN-221 in patients with SSTR2 expressing advanced gastroenteropancreatic (GEP) or lung or thymus or other neuroendocrine tumors or small cell lung cancer or large cell neuroendocrine carcinoma of the lung.

开始日期2016-12-08

申办/合作机构

Tarveda Therapeutics, Inc.

100 项与 SSTR2 x Tubulin 相关的临床结果

登录后查看更多信息

100 项与 SSTR2 x Tubulin 相关的转化医学

登录后查看更多信息

0 项与 SSTR2 x Tubulin 相关的专利（医药）

登录后查看更多信息

项与 SSTR2 x Tubulin 相关的文献（医药）

2016-12-13·Oncotarget

Synthetic paclitaxel-octreotide conjugate reversing the resistance of A2780/Taxol to paclitaxel in xenografted tumor in nude mice

Article

作者: Zhang, Xiao-Yu ; Wu, Yong-Ping ; Shen, Yang ; Fan, Li-Li ; Ren, Mu-Lan ; Chen, Xi

Peptide hormone-based targeted therapy to tumors has been studied extensively. Our previous study shows that somatostatin receptor expresses high level on drug-resistant human ovarian cancer. The paclitaxel-octreotide conjugate (POC) exhibits enhanced growth inhibition, as well as reduced toxicity, in paclitaxel-resistant human ovarian cancer cells. The aim of this study was to investigate the effect of targeted cytotoxicity and potential reversal mechanism of resistance in paclitaxel-resistant human ovarian cancer cells xenografted into nude mice. The SSTR2 shows higher expression levels in tumor tissue. Moreover, fluorescein-labeled POC displays favorable targeting in tumor cells. POC presents the perfect efficacy in inhibiting tumor growth and exerts lower or no toxic effects on normal tissues. Real-time PCR and Western Blotting has demonstrated that the mRNA and protein expressions of SSTR2 in POC group were significantly higher, while MDR1, α-tubulin, βIII-tubulin, VEGF and MMP-9 were significantly lower than in the other treatment groups and controls. Combined with the previous study in vitro, this study evaluates an effective approach on the treatment of paclitaxel-resistant ovarian cancer which expresses somatostatin receptor SSTR. Our investigation has also revealed the possible molecular mechanism of POC in treating the ovarian cancer, and therefore, provided a theoretical basis for the clinical application of this newly-invented compound.

2003-11-01·Journal of Biological Chemistry2区 · 生物学

Development of a Yeast Bioassay to Characterize G Protein-coupled Receptor Kinases

2区 · 生物学

Article

作者: Jeffrey L. Benovic ; Mark H. Pausch ; Lorena A. Kallal ; Beth Noble

G protein-coupled receptor kinases (GRKs) specifically bind and phosphorylate the agonist-occupied form of G protein-coupled receptors. To further characterize the mechanism of GRK/receptor interaction, we developed a yeast-based bioassay using strains engineered to functionally express the somatostatin receptor subtype 2 and exhibit agonist-dependent growth. Here, we demonstrate that agonist-promoted growth was effectively inhibited by co-expression with either wild type GRK2 or GRK5, whereas catalytically inactive forms of these kinases were without effect. In an effort to identify residues involved in receptor interaction, we generated a pool of GRK5 mutants and then utilized the bioassay to identify mutants selectively deficient in inhibiting agonist-promoted growth. This resulted in the identification of a large number of mutants, several of which were expressed, purified, and characterized in more detail. Two of the mutants, GRK5-L3Q/K113R and GRK5-T10P, were defective in receptor phosphorylation and also exhibited a partial defect in phospholipid binding and phospholipid-stimulated autophosphorylation of the kinase. In contrast, these mutants had wild type activity in phosphorylating the non-receptor substrate tubulin. To further characterize the function of the NH2-terminal region of GRK5, we generated a deletion mutant lacking residues 2-14 and found that this mutant was also severely impaired in receptor phosphorylation and phospholipid-promoted autophosphorylation. In addition, an NH2-terminal 14-amino acid peptide from GRK5 selectively inhibited receptor phosphorylation by GRK5 but had minimal effect on GRK2 activity. Based on these findings, we propose a model whereby the extreme NH2 terminus of GRK5 mediates phospholipid binding and is required for optimal receptor phosphorylation.