更新于：2024-11-01

Low-density lipoprotein x HSPA5

更新于：2024-11-01

基本信息

关联

项与 Low-density lipoprotein x HSPA5 相关的药物

PAT-SM6

靶点

HSPA5 x Low-density lipoprotein

作用机制

HSPA5抑制剂 [+1]

在研机构

Patrys Ltd. [+1]

原研机构

OncoMab GmbH

在研适应症

多发性骨髓瘤 [+1]

非在研适应症-

最高研发阶段临床2期

首次获批国家/地区-

首次获批日期1800-01-20

项与 Low-density lipoprotein x HSPA5 相关的临床试验

NCT01727778 / Completed临床1期

Open-label, Single-centre, Phase I, Multi-dose Escalating Study to Investigate the Safety and Preliminary Efficacy of an i.v. Infusion of the Anti-GRP78 Monoclonal IgM Antibody PAT-SM6 in Patients With Relapsed or Refractory Multiple Myeloma

Primary
- To evaluate the safety and tolerability of escalating doses of an intravenous (i.v.) infusion of PAT-SM6 in subjects with relapsed or refractory multiple myeloma.
Secondary
To evaluate the efficacy and pharmacodynamics by analysis of serum and urine M protein, serum free light chains (FLC) κFLC and λFLC, total immunoglobulins, β2-microglobulin, C-reactive protein (CRP), exploratory biomarkers and anti-PAT-SM6 antibodies.
To evaluate the duration of response and the progression free survival.

开始日期2012-10-01

申办/合作机构

Patrys Ltd.

ACTRN12610000733077 / Completed临床1期

A Single Dose, Dose Escalating, Phase I Clinical Trial to Determine the Safety of a Single Dose of PAT-SM6 Monoclonal Antibody in Patients with Recurrent In-Transit Cutaneous Melanoma

开始日期2010-08-27

申办/合作机构

Patrys Ltd.

100 项与 Low-density lipoprotein x HSPA5 相关的临床结果

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100 项与 Low-density lipoprotein x HSPA5 相关的转化医学

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0 项与 Low-density lipoprotein x HSPA5 相关的专利（医药）

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项与 Low-density lipoprotein x HSPA5 相关的文献（医药）

2019-07-01·Iranian journal of basic medical sciences4区 · 医学

Allantoin improves methionine-choline deficient diet-induced nonalcoholic steatohepatitis in mice through involvement in endoplasmic reticulum stress and hepatocytes apoptosis-related genes expressions.

4区 · 医学

ArticleOA

作者: Moslehi, Azam ; Komeili Movahhed, Tahereh ; Golchoob, Mohammad ; Ababzadeh, Shima

OBJECTIVESNon-alcoholic steatohepatitis (NASH) is defined by steatosis and inflammation in the hepatocytes, which can progress to cirrhosis and possibly hepatocellular carcinoma. However, current treatments are not entirely effective. Allantoin is one of the principal compounds in many plants and an imidazoline I receptor agonist as well. Allantoin has positive effects on glucose metabolism and inflammation. In this study, the effects of allantoin on the NASH induced animals and the pathways involved have been evaluated.MATERIALS AND METHODSC57/BL6 male mice received saline and allantoin as the control groups. In the next group, NASH was induced by the methionine-choline-deficient diet (MCD) for eight weeks. In the NASH+allantoin group, allantoin was injected four weeks in the mice feeding on an MCD diet. Histopathological evaluations, serum analysis, ELISA assay, and real-time RT-PCR were performed.RESULTSAllantoin administration decreased serum alanine aminotransferase (ALT), cholesterol, low-density lipoprotein (LDL), hepatic lipid accumulation, and liver tumor necrosis factor (TNFα) level. Also, treatment with allantoin down-regulated the gene expression of glucose-regulated protein 78 (GRP78), activating transcription factor 6 (AFT6), TNFα, sterol regulatory element binding proteins 1c (SREBP1c), fatty acid synthase (FAS), Bax/Bcl2 ratio, caspase3, and P53. On the other hand, peroxisome proliferator-activated receptor alpha (PPARα), apolipoprotein B (Apo B), and acetyl-coenzyme acetyltransferase 1 (ACAT1) gene expression increased after allantoin injection.CONCLUSIONThis study indicated that allantoin could improve animal induced NASH by changes in the expression of endoplasmic reticulum stress-related genes and apoptotic pathways.

2013-08-01·Melanoma Research4区 · 医学

Early development of PAT-SM6 for the treatment of melanoma

4区 · 医学

Article

作者: Rosenwald, Andreas ; Braendlein, Stephanie ; Eckstein, Miriam ; Hensel, Frank

Despite the recent development of novel therapies for patients with metastatic melanoma, this disease remains fatal in the majority of those who develop a relapse. Here, we report the preclinical and early clinical development of a novel IgM antibody PAT-SM6 that specifically binds to a cancer-specific isoform of glucose-regulated protein 78 (GRP78) and low-density lipoprotein. Finding a GRP78 cancer-specific form on the surface of cancer cells, but not normal cells in vivo, presents an opportunity for cancer-specific targeting. PAT-SM6 binding to the cell surface induces apoptosis in a variety of tumors, including melanoma. Recent studies show the specificity of PAT-SM6 binding to the surface of melanoma cells and primary tissue but not to normal tissue. They also confirm, for the first time, cell proliferation inhibition and apoptosis through classical apoptotic pathways as well as induction of lipid accumulation in melanoma cells. These in-vitro data are supported by positive in-vivo data using PAT-SM6 in a xenograft C8161 model. Furthermore, PAT-SM6 was well tolerated in pharmacokinetic/toxicology studies in monkeys. On the basis of these preclinical observations, a clinical study of PAT-SM6 was carried out in patients with 'in-transit' melanoma. Even with microdosing, histological analyses of tumor biopsies detected the presence of PAT-SM6 as well as apoptosis. Although there are many small molecules and monoclonal antibodies currently in clinical development for patients with melanoma, PAT-SM6 is the only therapeutic targeting the cancer-specific isoform of GRP78. These PAT-SM6 preclinical data and positive findings from the phase 1 safety study provide strong support for the further development of this novel antibody.

2013-02-01·Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology

[Effect of inflammatory stress on hepatic cholesterol accumulation and hepatic fibrosis in C57BL/6J mice].

Article

作者: Ruan, Xiong-zhong ; Liu, Yu ; Zhao, Lei ; Zuo, De-yu ; Chen, Ya-xi ; Zuo, Guo-qing

OBJECTIVETo investigate whether inflammatory stress exacerbates hepatic cholesterol accumulation and liver fibrosis using a C57BL/6J mouse model of chronic inflammation.METHODSTwelve male C57BL/6J mice were given a high-fat diet (15.0% fat, 1.25% cholesterol, 0.5% cholic acid) and randomly assigned to the normal control group (n=6; subcutaneously injected with 0.5 mL of isotonic saline, every other day for 14 weeks) or the chronic inflammation model group (n=6; subcutaneously injected with of 0.5 mL of 10% casein, every other day for 14 weeks). At the end of week 14, the animals were sacrificed and blood was collected from the left ventricle for serological analysis of inflammatory markers and lipid profile, including serum amyloid A (SAA), interleukin-6 (IL-6), total cholesterol (TC) and free cholesterol (FC), low-density lipoprotein (LDL), and high-density lipoprotein (HDL)). Extracted liver tissues were divided for use in histological analysis (lipid accumulation and fibrosis evaluated by Oil Red O, Sirius red and Masson's trichrome staining) and quantitative fluorescence real-time PCR (to measure b-actin normalized expression of TNF-a MCP1, SREBP-2, LDLr, HMGCoA-r, ATF-6, GRP78, BMP-7, TGF-b, and collagens type I and type IV). Comparisons between groups were made by the two-samples t-test or Satterthwaite t-approximation test, collagen type I and type IV.RESULTSCompared to the normal control group, the inflammation model group showed elevated serum IL-6 (12.55+/-4.75 vs. 32.41+/-7.42 pg/mL, P less than 0.01), reduced serum TC (14.82+/-1.56 vs. 10.62+/-0.48 mmol/L, P less than 0.01), up-regulated hepatic TNF-a mRNA expression (1.05+/-0.35 vs. 2.12+/-0.72, P less than 0.01), and elevated hepatic TC (12.10+/-2.57 vs. 23.21+/-8.75 mmol/L, P less than 0.05). In addition, the inflammation group showed abnormal lipid deposition, and increased and thickened reticular fibers. The livers of the inflammation group also showed up-regulated mRNA expression of SREBP-2 (normal control: 1.01+/-0.19 vs. 2.63+/-0.13, P less than 0.05), GRP78 (1.07+/-0.47 vs. 2.21+/-0.99, P less than 0.05), TGF-b (1.01+/-0.14 vs. 1.38+/-0.28, P less than 0.05), and collagen type I (1.02+/-0.27 vs. 1.71+/-0.51, P less than 0.05) and down-regulation of BMP-7 (1.01+/-0.15 vs. 0.55+/-0.25, P less than 0.01).CONCLUSIONActivation of the inflammatory system exacerbates hepatic cholesterol accumulation and hepatic fibrosis in C57BL/6J mice.