Abstract：
:Emerging evidence demonstrates that a c-Met antibody-drug conjugate (ADC) has superior efficacy and safety profiles compared with those of currently available small molecules or antibody inhibitors for the treatment of c-Met-overexpressing cancers. Here we described both the in vitro and in vivo efficacies of SHR-A1403, a novel c-Met ADC composed of a humanized IgG2 monoclonal antibody against c-Met conjugated to a novel cytotoxic microtubule inhibitor. SHR-A1403 showed high affinity to c-Met proteins derived from human or monkey and potent inhibitory effects in cancer cell lines with high c-Met protein expression. In mice bearing tumors derived from cancer cell lines or patient HCC tissues with confirmed c-Met overexpression, SHR-A1403 showed excellent anti-tumor efficacy. Antibody binding with c-Met contributed to SHR-A1403 endocytosis; the subsequent translocation to lysosomes and cytotoxicity of the released toxin are speculated to be predominant mechanisms underlying the anti-tumor activity of SHR-A1403. In conclusion, SHR-A1403 showed significant anti-tumor activity in cancer cell lines, xenograft mouse models and an HCC PDX model, which all have high c-Met levels. These data provide references for SHR-A1403 as a potential therapy for the treatment of cancers with c-Met overexpression.
journal_name
Acta Pharmacol Sinjournal_title
Acta pharmacologica Sinicaauthors
Yang CY,Wang L,Sun X,Tang M,Quan HT,Zhang LS,Lou LG,Gou SHdoi
10.1038/s41401-018-0198-0subject
Has Abstractpub_date
2019-07-01 00:00:00pages
971-979issue
7eissn
1671-4083issn
1745-7254pii
10.1038/s41401-018-0198-0journal_volume
40pub_type
杂志文章abstract：AIM:In order to elucidate the molecular mechanism underlying the cardioprotection afforded by schisandrin B (Sch B), the effect of Sch B treatment on the sensitivity of mitochondria to Ca2+-stimulated permeability transition (PT) was investigated in rat hearts under normal and ischemia-reperfusion (I-R) conditions. RE...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2007.00614.x
更新日期：2007-10-01 00:00:00
abstract：:Monoclonal antibodies are believed to be magic bullets and hold great potential for lots of biological process. About 100 μg of mAb109 was expressed in 5 × 106 cells after 10 days' immunization. 64Cu-NOTA-mAb109 was synthesized with the specific activity of 0.74 MBq/μg and high in vitro stability. The binding affinity...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/s41401-019-0294-9
更新日期：2020-01-01 00:00:00
abstract：AIM:To evaluate the therapeutic effects of gamichunggantang (GCT) on hyperlipidemia through high cholesterol diet model. GCT is an Oriental herbal medication, which has been used for the treatment of fatty liver, hyperlipidemia or alcoholic liver disease in Daejeon University Oriental Hospital, Korea since 1999. METHO...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2003-02-01 00:00:00
abstract：AIM:To investigate the role of c-Jun N-terminal protein kinase 1 and 2 (JNK1/2) and the main signal pathway for its activation in hydrogen peroxide (H(2)O(2)) induced apoptotic-like cortical cell death. METHODS:Using the model of oxidative stress induced by H(2)O(2), the expression and diphosphorylation of JNK1/2 was ...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2004-05-01 00:00:00
abstract：AIM:To explore the possible association of different polymorphic forms of human alpha-estrogen receptor (ER-alpha) and aryl hydrocarbon receptor gene (Ahr) with the risk to senile dementia in farmers in Shanghai suburb. METHODS:Senile dementia patients (n=52) were examined for ER-alpha and Ahr gene polymorphism genoty...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2003-07-01 00:00:00
abstract：AIM:Endothelium-dependent relaxations to certain neurohumoral substances are mediated by pertussis toxin-sensitive Gi/o protein. Our experiments were designed to determine the role, if any, of pertussis toxin-sensitive G-proteins in relaxations attributed to endothelium-derived hyperpolarizing factor (EDHF). METHODS:P...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2008.00905.x
更新日期：2008-12-01 00:00:00
abstract：:Resibufogenin (RBG) is a single compound isolated from Chansu, a traditional Chinese medicine obtained from the skin venom gland of the toad. Formulations of Chansu have been widely applied in China, Japan, and other Asian countries for a long time and are currently used as alternative medicines. However, there have b...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章,评审
doi：
更新日期：2001-04-01 00:00:00
abstract：AIM:To study the protein and mRNA expressions of pro-inflammatory and anti-inflammatory cytokines in the brain of rats with atherosclerosis (AS) and the effects of Ginkgo biloba extract (GbE) on expressions of cytokines. METHODS:The experimental model of AS in rats were established by intraperitioneal injection of vit...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2005.00106.x
更新日期：2005-07-01 00:00:00
abstract：:Tobacco use is estimated to be the largest single cause of premature death in the world. Nicotine is the major addictive substance in tobacco products. After cigarette smoking, nicotine quickly acts on its target, nicotinic acetylcholine receptors (nAChRs), which are widely distributed throughout the mammalian central...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2010.137
更新日期：2010-09-01 00:00:00
abstract：AIM:To investigate the antitumor actions of the Crotalus durissus neurotoxin (crotoxin) on human esophageal carcinoma (Eca-109) cells in vitro and transplanted esophageal Eca-109 tumors in nude mice. METHODS:The growth-inhibitory effect was analyzed in Eca-109 cells using MTT assay. Cell morphology changes in nuclei w...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2012.156
更新日期：2013-02-01 00:00:00
abstract：AIM:To study the effects of nimodipine on delayed cerebral injury in mice from subacute carbon monoxide (CO) exposure. METHODS:Mice were exposed to CO (100 mL/kg, ip) once a day, continuously for 7 d. After 7-d CO-exposure, mortality in mice, changes in learning ability and memory using passive avoidance test, the pat...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2001-05-01 00:00:00
abstract：:Wound healing impairment represents a particularly challenging clinical problem to which no efficacious treatment regimens currently exist. The factors ensuring appropriate intercellular communication during wound repair are not completely understood. Although protein-type mediators are well-established players in thi...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章,评审
doi：10.1111/j.1745-7254.2005.00058.x
更新日期：2005-03-01 00:00:00
abstract：AIM:Osteopontin (OPN), a multifunctional protein, has been reported to be protoxicant in acetaminophen hepatotoxicity. In this study, the mechanisms underlying the detrimental role of OPN in acetaminophen toxicity were explored. METHODS:Male C57BL/6 (wild-type, WT) and OPN(-/-) mice were administered with acetaminophe...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2012.47
更新日期：2012-08-01 00:00:00
abstract：:Cerebral edema is a pathological hallmark of various central nervous system (CNS) insults, including traumatic brain injury (TBI) and excitotoxic injury such as stroke. Due to the rigidity of the skull, edema-induced increase of intracranial fluid significantly complicates severe CNS injuries by raising intracranial p...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/s41401-020-00503-5
更新日期：2020-10-01 00:00:00
abstract：AIM:To investigate the expression of c-Met in peritoneal free cancer cells isolated from human gastric cancer ascites, and its relationship to peritoneal dissemination of gastric cancer. METHODS:Peritoneal free cancer cells (PFCCs) were isolated from ascites specimens of gastric cancer patients. c-Met expression in PF...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2011.205
更新日期：2012-04-01 00:00:00
abstract：AIM:To investigate the effect of peroxisome proliferator-activated receptor gamma (PPAR gamma ) activation on the growth of rat hepatic stellate cells (HSC) and transforming growth factor beta (TGF-beta)-induced connective tissue growth factor (CTGF) expression. METHODS:After being treated with various amounts of the ...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2006.00299.x
更新日期：2006-06-01 00:00:00
abstract：AIM:Omi is an ATP-independent serine protease that is necessary for neuronal function and survival. The aim of this study was to investigate the role of protease Omi in regulating differentiation of mouse neuroblastoma cells and to identify the substrate of Omi involved in this process. METHODS:Mouse neuroblastoma N2a...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2015.48
更新日期：2015-08-01 00:00:00
abstract：:Lactoferrin (Lf) is an iron-binding glycoprotein of the transferrin family, which is expressed in most biological fluids with particularly high levels in mammalian milk. Its multiple activities lie in its capacity to bind iron and to interact with the molecular and cellular components of hosts and pathogens. Lf can bi...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章,评审
doi：10.1038/aps.2013.200
更新日期：2014-05-01 00:00:00
abstract：AIM:To investigate whether total Panax notoginseng saponins (PNS) could protect endothelium of rabbit iliac artery against balloon endothelial denudation (BED) injury. METHODS:The morphology changes of the endothelium were observed with scanning electron microscope (SEM) and hematoxylin and eosin stain after BED of ra...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2004-09-01 00:00:00
abstract：:The fibroblast growth factor receptors (FGFRs) are increasingly considered attractive targets for therapeutic cancer intervention due to their roles in tumor metastasis and angiogenesis. Here, we identified a new selective FGFR inhibitor, C11, and assessed its antitumor activities. C11 was a selective FGFR1 inhibitor ...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/s41401-018-0191-7
更新日期：2019-06-01 00:00:00
abstract：AIM:Hydrogen peroxide (H2O2) is produced during liver transplantation. Ischemia/reperfusion induces oxidation and causes intracellular Ca2+ overload, which harms liver cells. Our goal was to determine the precise mechanisms of these processes. METHODS:Hepatocytes were extracted from rats. Intracellular Ca2+ concentrat...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2008.4
更新日期：2009-01-01 00:00:00
abstract：AIM:To study and establish a proteome reference map and regulation network of neonatal rat cardiomyocyte. METHODS:Cultured cardiomyocytes of neonatal rats were used. All proteins expressed in the cardiomyocytes were separated and identified by two-dimensional polyacrylamide gel electrophoresis (2-DE) and matrix-assist...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2011.86
更新日期：2011-09-01 00:00:00
abstract：AIM:To determine the postshock activation patterns with both successful and failed shocks in a canine model of ventricular fibrillation, and whether piniacidil, an early after-depolarization (EAD) inhibitor, altered the defibrillation threshold (DFT) and postshock activation patterns. METHODS:In 6 beagles, a basket ca...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2012.96
更新日期：2012-12-01 00:00:00
abstract：AIM:To investigate the effects of rapamycin on glutamate uptake in cultured rat astrocytes expressing N-terminal 552 residues of mutant huntingtin (Htt-552). METHODS:Primary astrocyte cultures were prepared from the cortex of postnatal rat pups. An astrocytes model of Huntington's disease was established using the ast...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2011.162
更新日期：2012-03-01 00:00:00
abstract：AIM:Fibroblast growth factor 7 (FGF7) is involved in a number of physiological and pathological processes, including lung disease. However, relatively little is known about the effect of FGF7 gene polymorphisms on chronic obstructive pulmonary disease (COPD) susceptibility. This study aimed to investigate the associati...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2012.69
更新日期：2012-08-01 00:00:00
abstract：AIM:To investigate the proliferation of vascular smooth muscle cells (VSMC) affected by ginsenoside Rg1 and further explore the molecular mechanism of ginsenoside Rg1 using proteomics. METHODS:The proliferation of VSMC was measured by MTS assay kit and flow cytometry. Proteomic alterations were analyzed using two-dime...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2006.00331.x
更新日期：2006-08-01 00:00:00
abstract：:Excessive and abnormal vessel growth plays a critical role in the pathogenesis of many diseases, such as cancer. Angiogenesis is one of the hallmarks of cancer growth, invasion, and metastasis. Discovery of novel antiangiogenic agents would provide new insights into the mechanisms of angiogenesis, as well as potential...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/s41401-019-0224-x
更新日期：2019-11-01 00:00:00
abstract：:Telomere shortening is associated with idiopathic pulmonary fibrosis (IPF), a high-morbidity and high-mortality lung disease of unknown etiology. However, the underlying mechanisms remain largely unclear. In this study, wild-type (WT) mice with normal telomeres and generation 3 (G3) or G2 telomerase RNA component (TER...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/s41401-018-0007-9
更新日期：2018-11-01 00:00:00
abstract：AIM:Filamin binding LIM protein 1, also known as migfilin, is a skeleton organization protein that binds to mitogen-inducible gene 2 at cell-extracellular matrix adhesions. The aim of this study was to investigate the role of migfilin in cisplatin-induced apoptosis in human glioma cells, to determine the functional dom...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2012.123
更新日期：2012-10-01 00:00:00
abstract：AIM:To evaluate the pharmacokinetic characteristics of L-valyl-ara-C, a peptidomimetic prodrug of ara-C. METHODS:After the synthesis of L-valyl-ara-C, the in vitro stability of L-valyl-ara-C was examined in various biological media. Plasma pharmacokinetic profiles of ara-C and L-valyl-ara-C were also evaluated in rats...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2007.00474.x
更新日期：2007-02-01 00:00:00
