公开(公告)号：US20250064837A1

公开(公告)日：2025-02-27

申请号：US18923448

申请日：2024-10-22

Applicant: ShanghaiTech University

Inventor： Xiaobao Yang ,  Biao Jiang ,  Renhong Sun ,  Chaowei Ren ,  Ning Sun ,  Ying Kong ,  Yan Li ,  Jinju Chen ,  Qianqian Yin ,  Xiaoling Song ,  Quanju Zhao ,  Xing Qiu

IPC: A61K31/675 ,  A61K31/138 ,  A61K31/454 ,  A61K31/496 ,  A61K31/5025 ,  A61K31/506 ,  A61K31/519 ,  A61K31/5517 ,  A61K45/06 ,  A61K47/54 ,  A61K47/60 ,  A61P35/00

Abstract: The present disclosure relates to compounds of formula (I) and their anti-tumor uses, and their intermediates of formula (III), and uses of the intermediates. The compound of formula (I) has a degrading effect on a specific target protein, which is mainly composed of three parts. The first part is a small molecule compound (SMBP, Small Molecules Binding Protein) that can bind to a protein, the second part LIN is a linker, and the three-part ULM is a ubiquitin ligand (ULM, Ubiquitin Ligase Binding Moiety), wherein SMBP is covalently bound to LIN, and LIN is covalently bound to ULM. A series of compounds designed and synthesized in the present disclosure have a wide range of pharmacological activities, including the functions of degrading specific proteins and/or inhibiting activities of specific proteins, and thus can be used in related tumor treatments.

公开(公告)号：US12226424B2

公开(公告)日：2025-02-18

申请号：US17046690

申请日：2019-04-09

Applicant: ShanghaiTech University

Inventor： Xiaobao Yang ,  Biao Jiang ,  Renhong Sun ,  Chaowei Ren ,  Ning Sun ,  Ying Kong ,  Yan Li ,  Jinju Chen ,  Qianqian Yin ,  Xiaoling Song ,  Quanju Zhao ,  Xing Qiu

IPC: A61K31/675 ,  A61K31/138 ,  A61K31/454 ,  A61K31/496 ,  A61K31/5025 ,  A61K31/506 ,  A61K31/519 ,  A61K31/5517 ,  A61K45/06 ,  A61K47/54 ,  A61K47/60 ,  A61P35/00

Abstract: The present disclosure relates to compounds of formula (I) and their anti-tumor uses, and their intermediates of formula (III), intermediates of formula (IV), and uses of the intermediates. The compound of formula (I) has a degrading effect on a specific target protein, which is mainly composed of three parts. The first part is a small molecule compound (SMBP, Small Molecules Binding Protein) that can bind to a protein, the second part LIN is a linker, and the three-part ULM is a ubiquitin ligand (ULM, Ubiquitin Ligase Binding Moiety), wherein SMBP is covalently bound to LIN, and LIN is covalently bound to ULM. A series of compounds designed and synthesized in the present disclosure have a wide range of pharmacological activities, including the functions of degrading specific proteins and/or inhibiting activities of specific proteins, and thus can be used in related tumor treatments.

公开(公告)号：US11639343B2

公开(公告)日：2023-05-02

申请号：US17015319

申请日：2020-09-09

Applicant: ShanghaiTech University

Inventor： Xiaobao Yang ,  Biao Jiang ,  Qianqian Yin ,  Jinju Chen ,  Quanju Zhao ,  Chaowei Ren ,  Renhong Sun ,  Ning Sun ,  Xing Qiu ,  Ying Kong ,  Yan Li ,  Linyi Liu

IPC: C07D401/14 ,  C07D417/14 ,  A61P35/02 ,  A61K45/06

Abstract: The present disclosure provides a compound of formula (I) targeting and degrading BCR-ABL protein and its use in the field of antitumor. The compound of formula (I) shows degradation and inhibitory effects on BCR-ABL target protein, which is mainly comprised of four moieties, wherein the first moiety (BCR-ABL-TKIs) is compound moiety with BCR-ABL tyrosine kinase inhibited activity; the second moiety (the LIN) is link units; the third moiety (the ULM) is a small molecule ligand for VHL or CRBN proteases with ubiquitination; and the four moiety (the group A) is carbonyl group that covalently binds to BCR-ABL-TKIs and LIN, and the LIN is further covalently bonded to ULM. A series of compounds designed and synthesized by the present disclosure shows extensive pharmacological effective, which function to degrade BCR-ABL protein and inhibit BCR-ABL effective, and can be utilized for treating relevant tumor.

公开(公告)号：US20220117982A1

公开(公告)日：2022-04-21

申请号：US17046690

申请日：2019-04-09

Applicant: ShanghaiTech University

Inventor： Xiaobao Yang ,  Biao Jiang ,  Renhong Sun ,  Chaowei Ren ,  Ning Sun ,  Ying Kong ,  Yan Li ,  Jinju Chen ,  Qianqian Yin ,  Xiaoling Song ,  Quanju Zhao ,  Xing Qiu

IPC: A61K31/675 ,  A61K45/06 ,  A61K47/54 ,  A61K47/60 ,  A61K31/506 ,  A61K31/496 ,  A61K31/5025 ,  A61K31/138 ,  A61K31/5517 ,  A61K31/519 ,  A61K31/454 ,  A61P35/00

Abstract: The present disclosure relates to compounds of formula (I) and their anti-tumor uses, and their intermediates of formula (III), intermediates of formula (IV), and uses of the intermediates. The compound of formula (I) has a degrading effect on a specific target protein, which is mainly composed of three parts. The first part is a small molecule compound (SMBP, Small Molecules Binding Protein) that can bind to a protein, the second part LIN is a linker, and the three-part ULM is a ubiquitin ligand (ULM, Ubiquitin Ligase Binding Moiety), wherein SMBP is covalently bound to LIN, and LIN is covalently bound to ULM. A series of compounds designed and synthesized in the present disclosure have a wide range of pharmacological activities, including the functions of degrading specific proteins and/or inhibiting activities of specific proteins, and thus can be used in related tumor treatments.

公开(公告)号：US20220016102A1

公开(公告)日：2022-01-20

申请号：US17296165

申请日：2019-11-20

Applicant: ShanghaiTech University

Inventor： Xiaobao Yang ,  Biao Jiang ,  Renhong Sun ,  Chaowei Ren ,  Ning Sun ,  Xing Qiu

IPC: A61K31/454 ,  C07D401/04 ,  C07D417/12 ,  A61K31/427 ,  A61P35/00

Abstract: The present disclosure relates to an ER protein regulator compound represented by formula (I) and use thereof. LIN in the compound represented by formula (I) is a linker; ULM is a small-molecule ligand of VHL or CRBN protease having a ubiquitylation function; and group X is CH2, O or NH, and group X is covalently linked to ULM by means of the linker LIN. The designed and synthesized compounds of the present disclosure have wide pharmacological activity, has the function of regulating ER protein and inhibiting the activity of tumors, and can be used for preventing and/or treating diseases and disorders associated with estrogen receptors, or related tumor treatment.