15 results about "Apoptosis protein" patented technology

This disclosure features structurally-stabilized and / or cysteine-reactive peptide inhibitors for selective targeting of BFL-1, or dual targeting of BFL-1 and MCL-1. Also disclosed are methods of using such structurally-stabilized and cysteine-reactive peptides in the treatment of BFL-1- and / or MCL-1-expressing or -dependent cancers or diseases of cellular excess (e.g., autoimmune or inflammatory conditions). Also provided are combination therapies comprising such structurally-stabilized and / or cysteine-reactive peptides and inhibitors of the DNA damage response pathway, such as an ATM kinase inhibitor, ATR kinase inhibitor, CHK1 / 2 inhibitor, or PARP inhibitor; or an inhibitor of MCL-1, or a selective inhibitor of BCL-2, or an inhibitor of BCL-2 / BCL-XL, for the treatment of BFL-1-expressing or -dependent cancers (e.g., AML), BFL-1 and MCL-1-expressing or -dependent cancers, or diseases of cellular excess (e.g., autoimmune or inflammatory conditions).

The present application provides an indole derivative and a preparation method and application thereof. The preparation method comprises the following steps: dissolving copper acetate and triethylamine in isopropyl alcohol, stirring until completely dissolved to obtain a reaction medium; adding 5-bromo indigo and indole into the reaction medium, fully stirring at room temperature until the reaction is completely converted; removing the reaction solvent by distillation to obtain a crude product, purifying and recrystallizing to obtain a high-purity solid powder of the indole derivative. The indole derivative has a significant inhibitory effect on tyrosinase, melanin production and transfer; has high antioxidant capacity for scavenging intracellular active oxygen free radicals; through the mechanisms of affecting the membrane potential of mitochondria, activating the related apoptosis signaling pathway and promoting the expression of apoptosis proteins, etc., the A549 cell is prompted to enter the apoptosis program, thereby providing a new potential strategy and research direction for the apoptosis regulation of tumor cells, and having important research value and application prospect.

The invention belongs to the technical field of biological medicines, and particularly relates to lipid nanoparticles as well as a preparation method and application thereof. The invention discloses a lipid nanoparticle. The material of the lipid nanoparticle comprises phospholipid and cholesterol. According to the invention, a lipid nano-carrier delivery system entrapped with apoptotic protein Bax is prepared through a microfluidic technology, and high encapsulation rate and stable delivery of protein drugs are realized. The nano-carrier delivery system capable of actively encapsulating the lipidosome realizes targeted delivery to senescent cells in vivo, so that senescent cell apoptosis is effectively induced, the proportion of senescent cells in tissues is reduced, and a new thought and means are provided for anti-aging treatment.

The invention discloses a radiotherapy activated self-assembled polypeptide magnetic resonance contrast agent as well as a preparation method and application thereof. The magnetic resonance contrast agent is prepared by sequentially connecting a tumor targeting peptide module, a radiotherapy activation peptide module, an assembly peptide module and a contrast molecule fragment module through solid-phase synthesis. The magnetic resonance contrast agent can perform targeted recognition in tumor-bearing mice and penetrate tumor cells, and can perform self-assembly under the action of apoptosis protease generated by induction after radiotherapy to form nanofibers, so that the intracellular residence time is prolonged, T1 weighted magnetic resonance imaging signals are enhanced, and the imaging contrast ratio of tumor parts after radiotherapy is further improved. The magnetic resonance contrast agent provides higher accuracy and safety for tumor radiotherapy guided by magnetic resonance imaging, can be used as a novel molecular probe for monitoring the tumor radiotherapy process and effect in real time, and has a good clinical application prospect.

The invention designs a new application of grape seed procyanidine in prevention and treatment of cataract. The method comprises the following steps: constructing a cataract injury model by inducing rabbit crystalline lens oxidative injury with hydrogen peroxide, culturing by adopting a domestic rabbit crystalline lens, detecting the activity of total superoxide dismutase, glutathione peroxidase and catalase and the content of malondialdehyde by observing the opacity and structural form of the crystalline lens, and detecting the expression of apoptosis regulation proteins BCL-2 and BAX in combination with immunohistochemistry. And the protective effect and molecular mechanism of the grape seed procyanidine on crystalline lens injury are researched. Researches show that the grape seed procyanidine has a protective effect on hydrogen peroxide induced rabbit crystalline lens injury, and the mechanism of the grape seed procyanidine is related to an antioxidant effect and adjustment of BCL-2 / BAX apoptotic protein; rabbit eye stimulation experiments prove that the grape seed procyanidine has no stimulation or only slight stimulation to rabbit eyes. Therefore, the grape seed procyanidine can prevent cataract, is a potential cataract treatment medicine, provides a new way for development of related medical products such as eye drops, and has good clinical application value.

The invention belongs to the field of biological medicines, and discloses application of a Meis1 inhibitor in preparation of a medicine for relieving acute renal tubule injury. Aiming at the clinical problem that acute kidney injury (AKI) lacks a specific drug, the invention firstly discovers that marrow cytophilic virus integration site 1 (Meis1) is obviously up-regulated in AKI kidney tissues, and a folic acid (FA) and ischemia reperfusion (IR) double-animal model proves that the Mis1 inhibitor MEISi-2 (0.1-1mg / kg) is given; and intraperitoneal injection is carried out 1 day to 2 days before injury), so that the serum creatinine can be obviously reduced, the pathological injury of renal tubules (PAS score is more than or equal to 50%) can be improved, and injury markers KIM-1 / NGAL and apoptotic protein Cleaved Caspase 3 can be inhibited. In-vitro experiments further prove that MEISi-2 (1 [mu] M) can relieve apoptosis of renal tubular epithelial cells induced by hypoxia and reoxygenation (the apoptosis rate reaches 21.9%) by inhibiting Meis1. The invention also provides a pharmaceutical composition containing MEISi-2 (10-100 [mu] g / mL) and a normal saline injection preparation. The scheme is high in safety (no liver and kidney cardiotoxicity is found), and a brand new means is provided for targeted therapy of AKI.

The present disclosure relates to bifunctional compounds, which find utility as modulators of Kirsten rat sarcoma protein (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand which binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation / inhibition of target protein. Diseases or disorders that result from aggregation, accumulation, and / or overactivation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

The invention provides application of frankincense processed product volatile oil in preparation of a medicine. The medicine is used for resisting apoptosis or promoting cell proliferation. The frankincense processed product volatile oil can activate a cAMP signal channel and promote the expression of PKA so as to influence a downstream signal channel, inhibit the phosphorylation of pro-apoptotic protein Bad and promote the expression of anti-apoptotic proteins Bcl-2 and Bcl-xl, thereby effectively inhibiting the apoptosis. Therefore, when the frankincense processed product volatile oil is prepared into the medicine, cell apoptosis can be effectively inhibited, and then cell proliferation is promoted.

Methods of administering inhibitors of apoptosis protein (“IAP”), or pharmaceutically acceptable salts thereof, for the treatment of a human patient having locally advanced squamous cell carcinoma are provided.

The application belongs to the technical field of biomedicine, and particularly relates to application of exogenous recombinant protein ANXA5 in preparation of a medicine for treating cerebral hemorrhage. The application discloses that the expression level of ANXA5 is increased after cerebral hemorrhage; by adding the recombinant ANXA5 protein, the expression level of an iron death related protein can be reduced; meanwhile, the expression level of an apoptosis protein is reversed, the oxidative stress level is slightly reduced, and the levels of MDA and active oxygen water are obviously decreased, which proves that the recombinant protein ANXA5 plays an inhibiting role on neuron iron death after cerebral hemorrhage. The application provides a new type of medicine basis for using the recombinant protein ANXA5 as a treatment for cerebral hemorrhage, especially iron death caused after cerebral hemorrhage.

The invention discloses a product for reducing the phosphorylation level of a Serine 99 site of a BAD protein and an anti-tumor application of the product. The invention provides the BAD S99A mutant, phosphorylation is specifically blocked through the BAD S99A mutant, accurate regulation and control of an apoptosis pathway are achieved, and the problems that in the prior art, due to the fact that the phosphorylation state of BAD cannot be controlled, the apoptosis activation efficiency is low, and the mechanism is indefinite are solved.

The invention discloses an application of aucubin in preparation of a medicine for improving ischemia-reperfusion pan apoptosis of lower limbs, on one hand, an in-vitro cell experiment shows that the aucubin treatment can improve the cell viability of a mouse primary gastrocnemius muscle pan apoptosis model and reduce the cell apoptosis, so that the scratch healing rate is improved; meanwhile, the expression of related death proteins of a pan-apoptotic cell model can be reduced; on the other hand, animal in-vivo experiments show that aucubin can regulate a TNF-NFKB pathway through negative feedback and inhibit polarization of M1 inflammatory macrophages, so that expression of lower limb ischemia reperfusion pan-apoptosis protein is reduced, and the effect of improving pan-apoptosis caused by lower limb ischemia reperfusion is achieved.

The present application relates to the technical field of renal cell carcinoma, and particularly relates to a method for predicting the lipid metabolism regulation mechanism of renal cell carcinoma, which is characterized by the following steps: determining the expression difference of EMT, cell proliferation and apoptosis proteins in groups through molecular detection, and determining the difference of fat pathway genes, oil accumulation degree and fat factor expression level in groups, and determining the correlation between lipid metabolism and GAD2, the present project first proposes the miR-metabolic enzyme-lipid pool regulation axis, which is different from the traditional mode of miR directly targeting proliferation genes. Previous studies have focused on the regulation of miRNA on directly related genes such as tumor cell proliferation and apoptosis, and the present project starts from the fat metabolism pathway and deeply explores the regulation of miR-362-5p targeting GAD2 gene on the progression of renal cell carcinoma (RCC). This innovation provides a new perspective and theoretical framework for RCC research, and is expected to open up a new treatment idea, and a systematic research system from clinical samples, cell experiments, molecular detection to animal experiments is constructed.

Disclosed herein are novel 2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine or 1,2,3,4-tetrahydropyrido[2,3-b][1,4]oxazepine derivatives used as antagonists of IAPs (Inhibitors Apoptosis Proteins), also known as Smac mimetics. Disclosed herein is the use of these antagonists for inducing or sensitizing cells to the induction of apoptotic cell death, and the use of such compounds for treating proliferative disease such as cancer.

The invention belongs to the technical field of biological medicines, and particularly relates to application of a PCBP2 overexpression vector in preparation of an MIRI treatment medicine. In order to solve the problem that effective targets for resisting apoptosis of myocardial cells are deficient in treatment of apoptosis-dominated myocardial ischemia reperfusion injury, the invention provides application of a PCBP2 overexpression vector in preparation of an MIRI treatment medicine, and endogenous protein PCBP2 down-regulated in ischemia reperfusion injury is accurately up-regulated through the overexpression vector. The myocardial cell apoptosis balance is efficiently regulated and controlled: the apoptosis rate of the myocardial cells is directly reduced by remarkably up-regulating anti-apoptotic protein Bcl-2 and down-regulating pro-apoptotic protein Bax, and the excessive apoptosis process of the myocardial cells in an apoptosis-dominant injury scene is blocked from the molecular level. According to the invention, dual protection on the myocardial structure and function is realized at the same time, the cardiac function can be improved, the myocardial infarction area can be reduced, and a new candidate strategy is provided for anti-apoptosis treatment of apoptosis-dominated myocardial ischemia-reperfusion injury.