Autotac Inc.

Seoul National University

Goldstar Electron Co., Ltd.

Autotac Bio

Yong Tae Kwon

Ki Woon Sung

Eui Jung Jung

Chan Hoon Jung

Srinivasrao Ganipisetti

Su Ran Mun

Chang Hoon Ji

Hee Yeon Kim

Hyun Tae Kim

Jeong Eun Na

Su Jin Kim

Ji Eun Lee

Bo Yeon Kim

Chang Min Park

Min Ju Lee

Hyunjoo Cha

Eun Hye Jeong

Tae Hyun Bae

Chang An Jung

Ji-eun Yu

Young Dong Yoo

Yu Jin Seo

Ah Jung Heo

Ha Rim Choi

The present invention relates to a novel p62 ligand compound, a stereoisomer, hydrate, solvate or prodrug thereof, and a pharmaceutical or food composition for preventing or treating misfolded protein diseases comprising the same as an active ingredient. The p62 ligand compound according to the present invention can be usefully used as a pharmaceutical composition for the prevention, amelioration or treatment of various proteinopathies by activating selective autophagy in cells and thus selectively eliminating in vivo proteins, organelles and aggregates.

P62 ligand compound, and composition for preventing, ameliorating or treating proteinopathies comprising the same

One aspect of the disclosure relates to a cargo delivery system comprising an autophagy targeting ligand and a target-binding ligand. In one aspect of the disclosure, by comprising an autophagy targeting ligand, cargo, which is a target-binding ligand that specifically binds to a target, is delivered to the p62 protein and autophagy is activated, so that depending on the type of target-binding ligand used, a target to be degraded can be selectively and directly removed. Accordingly, the cargo delivery system according to an aspect of the disclosure may be used in pharmaceutical compositions or food compositions for preventing, alimerating, and treating various diseases.

Cargo delivery system and composition comprising the same

The present invention relates to a novel AUTOTAC chimeric compound in which a new p62 ligand and a target-binding ligand are connected by a linker, a stereoisomer, hydrate, solvate or prodrug thereof, and a pharmaceutical or food composition for the prevention or treatment of diseases by degrading the target protein including the same as an active ingredient. They can target specific proteins to adjust their concentrations, and can also deliver drugs and other small molecule compounds to lysosomes. The AUTOTAC chimeric compound according to the present invention can be usefully used as a pharmaceutical composition for the prevention, amelioration or treatment of various diseases by selectively eliminating specific proteins.

AUTOTAC chimeric compound, and composition for preventing, ameliorating or treating diseases through targeted protein degradation comprising the same

The present invention provides a compound represented by the following Chemical Formula 1 or a pharmaceutically acceptable salt thereof which can be effectively used for preventing or treating obesity or metabolic syndrome, and a pharmaceutical composition comprising the same.

Compound and pharmaceutical composition for preventing or treating obesity or metabolic syndrome comprising thereof

The present invention relates to a novel p62 ligand compound, a stereoisomer, hydrate, solvate or prodrug thereof, and a pharmaceutical or food composition for preventing or treating proteinopathies comprising the same as an active ingredient. The p62 ligand compound according to the present invention can be usefully used as a pharmaceutical composition for the prevention, amelioration or treatment of various proteinopathies by activating autophagy in cells and thus selectively eliminating in vivo proteins, organelles and aggregates.

The present specification discloses a novel benzyloxy pyridine derivative compound represented by Chemical Formula 1, a salt thereof, a stereoisomer thereof, a hydrate thereof, or a solvate thereof, and novel uses thereof. The uses comprise the uses in the preparation of a composition for activating autophagy, a composition for activating p62 protein, a composition for inducing oligomerization of p62 protein, or a composition for ameliorating, preventing or treating a disease caused by misfolded protein.

Benzyloxy pyridine derivatives and uses thereof

The pharmacokinetics and key technologies of the present invention are summarized in. Particularly, malignant misfolded proteins such as mutant huntingtin and alpha-synuclein are coagulated and grow into oligomeric coagulum ({circle around (1)}, {circle around (2)}, fibrillar coagulum ({circle around (3)}) and eventually inclusion body ({circle around (4)}). Young neurons produce a large amount of Nt-Arg through N-terminal arginylation ({circle around (5)}) of vesicle chaperones such as BiP secreted into the cytoplasm, and then arginylated BiP (R-BiP) is secreted binds to the misfolded proteins ({circle around (6)}). As a ligand, the Nt-Arg of R-BiP binds to the p62 ZZ domain ({circle around (7)}), and the normally inactivated closed form of p62 is changed to an open form, leading to structural activation ({circle around (8)}). As a result, PB1 and LC3-binding domains are exposed. The PB1 domain induces oligomerization ({circle around (9)}), leading to the concentration as a p62 body ({circle around (10)}) that is a coagulum capable of being degraded by autophagy. Then, p62 binds to LC3, which is protruding from the autopagosomal membranes, leading to the completion of autophagy targeting ({circle around (11)}) and lysosomal proteolysis. Since autophagy proteolysis including steps ({circle around (5)})-({circle around (11)}) is strong in young neurons, cytotoxic protein coagulums ({circle around (1)}-{circle around (5)}) do not accumulate. However in aged neurons, autophagy proteolysis including steps {circle around (5)}-{circle around (11)} is weakened, and protein coagulums ({circle around (1)}-{circle around (5)}) accumulate and become cytotoxic. In this invention, p62 is intentionally activated ({circle around (12)}, {circle around (13)}) by using low mass ligands of the p62 ZZ domain to effectively remove huntingtin and alpha-synuclein protein coagulums. Particularly, in step {circle around (12)}, p62 ligated with a ligand accelerates the oligomerization of p62-R-BiP-misfolded protein ({circle around (9)}) and the formation of autophagy coagulum ({circle around (10)}). In step ({circle around (13)}), the ligand-p62 conjugate acts as an autophagy activator ({circle around (14)}) to induce the synthesis of LC3 and the conversion of LC3-I into LC3-II in order to accelerate the formation of autophagosomes ({circle around (15)}).

Prevention and treatment of neurodegenerative diseases through autophagy activity mediated by a synthetic ligand or arginylated BIP binding to the P62 ZZ domain

A semiconductor package directly soldering the chip pad to the inner leads and a method for producing the package are disclosed. The chip pad is placed on the bottom surface of an inner lead extending from opposed sides of the chip pad. A plurality of inner lead holes are formed in the interconnection parts between the inner leads and the auxiliary leads. A solder resist film bonded to the lead frame has a plurality of solder resist holes communicating with the inner lead holes. In order to produce the package, a lead pattern is formed and the lead frame is etched using the lead pattern, so that the inner lead holes and the solder resist holes are formed and the inner leads come into direct contact with the chip pad. Thereafter, the chip pad is soldered to the inner leads.

Thin soldered semiconductor package

Growing community of inventors

Seoul, South Korea

Yong Tae Kwon