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：US11771709B2

公开(公告)日：2023-10-03

申请号：US16902172

申请日：2020-06-15

Applicant: ShanghaiTech University

Inventor： Xiaobao Yang ,  Biao Jiang ,  Xiaoling Song ,  Haifan Lin ,  Ning Sun ,  Jinju Chen ,  Xing Qiu ,  Chaowei Ren ,  Ying Kong

IPC: A61K31/662 ,  A61P35/00 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/496 ,  A61K31/501 ,  A61K31/506 ,  A61K31/519 ,  A61K45/06

CPC classification number: A61K31/662 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/496 ,  A61K31/501 ,  A61K31/506 ,  A61K31/519 ,  A61P35/00 ,  A61K45/06

Abstract: A compound of formula (I) and its antitumor application are disclosed. The compounds of formula (I) have degradation and inhibitory effects on ALK target proteins. They are mainly composed of four parts: the first part, ALK-TKI, being compounds with ALK tyrosine kinase inhibitory activity; the second part, LIN, being different kinds of linker (Linker); the third part, the ULM, being a small molecule ligand (ULM, ubiquitin ligase binding moiety) with ubiquitination of VHL, CRBN or other proteases; and the fourth part, the group A, being a carbonyl group or absent, which covalently bond ALK-TKI to LIN, wherein LIN and ULM are covalently bonded. A series of compounds designed and synthesized by the present disclosure have wide pharmacological activities, have functions of degrading ALK protein and inhibiting ALK activity, and can be used for related tumor treatment.

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：US20200306273A1

公开(公告)日：2020-10-01

申请号：US16902172

申请日：2020-06-15

Applicant: ShanghaiTech University

Inventor： Xiaobao Yang ,  Biao Jiang ,  Xiaoling Song ,  Haifan Lin ,  Ning Sun ,  Jinju Chen ,  Xing Qiu ,  Chaowei Ren ,  Ying Kong

IPC: A61K31/662 ,  A61K31/506 ,  A61K31/4439 ,  A61K31/496 ,  A61K31/454 ,  A61K31/519 ,  A61K31/501 ,  A61P35/00

Abstract: A compound of formula (I) and its antitumor application are disclosed. The compounds of formula (I) have degradation and inhibitory effects on ALK target proteins. They are mainly composed of four parts: the first part, ALK-TKI, being compounds with ALK tyrosine kinase inhibitory activity; the second part, LIN, being different kinds of linker (Linker); the third part, the ULM, being a small molecule ligand (ULM, ubiquitin ligase binding moiety) with ubiquitination of VHL, CRBN or other proteases; and the fourth part, the group A, being a carbonyl group or absent, which covalently bond ALK-TKI to LIN, wherein LIN and ULM are covalently bonded. A series of compounds designed and synthesized by the present disclosure have wide pharmacological activities, have functions of degrading ALK protein and inhibiting ALK activity, and can be used for related tumor treatment.