公开(公告)号：US20170135979A1

公开(公告)日：2017-05-18

申请号：US14940406

申请日：2015-11-13

Applicant: Macau University of Science and Technology

Inventor： Xiao Jun Yao ,  Lai Han Leung ,  Lian Xiang Luo ,  Liang Liu

IPC: A61K31/343

CPC classification number: A61K31/343

Abstract: The present invention relates to the administration of a novel compound advantageously efficacious as PDEδ inhibitor and its effects on subjects with cancer. More specifically, the present invention is directed to a method for administering a compound having favorable geometric properties for interacting with the PDEδ prenyl-binding pocket, namely has certain structural components such as a three-cyclic backbone and at least one benzoyl-moiety in a side chain having at least two substituents containing highly electronegative atoms and being linked to the backbone via an aliphatic chain, for treating a subject suffering from a disease such as cancer, in particular non-small-cell lung cancer. The presence of said structural components particularly contributes to an advantageous interaction with PDEδ, in particular with amino acids deep in the binding pocket. The present invention further provides a method to target tumor cells harboring an RAS gene mutation as well as pharmaceutical compositions comprising said compound.

公开(公告)号：US09526722B1

公开(公告)日：2016-12-27

申请号：US14744042

申请日：2015-06-19

Applicant: Macau University of Science and Technology

Inventor： Xiao Jun Yao ,  Lai Han Leung ,  Lian Xiang Luo ,  Yan Ling Zhou ,  Liang Liu

IPC: A01N43/42 ,  A61K31/444 ,  A61K31/4745

CPC classification number: A61K31/4745

Abstract: The present invention provides a compound that inhibits activity of oncogenic ROS1, a composition comprising said compound. The present invention also provides the use of said composition for treating cancer.

Abstract translation: 本发明提供抑制致癌ROS1活性的化合物，其是包含所述化合物的组合物。 本发明还提供了所述组合物用于治疗癌症的用途。

公开(公告)号：US09962378B2

公开(公告)日：2018-05-08

申请号：US14927825

申请日：2015-10-30

Applicant: Macau University of Science and Technology

Inventor： Xiao Jun Yao ,  Lai Han Leung ,  Lian Xiang Luo ,  Liang Liu

IPC: A61K31/4743

CPC classification number: A61K31/4743

Abstract: The administration of a compound advantageously efficacious as ROS1 inhibitor and its effect on subjects with cancer includes administering a compound having certain structural components such as a quinoline moiety in the backbone and at least one tertiary amine containing moiety in a side chain as well as heteroatoms, in particular oxygen atoms, present in the backbone and the side chain for treating a subject suffering from a disease such as cancer. The presence of such structural components allows for an advantageous interaction with the ROS1 kinase domain, in particular with the hinge region. The administered compounds represent a highly promising opportunity in particular for patients bearing ROS1-dependent cancer. A method for targeting tumor cells harboring an abnormality in ROS1 gene includes contacting a cell with compounds of the present invention as well as pharmaceutical compositions comprising such compounds.

公开(公告)号：US09782400B2

公开(公告)日：2017-10-10

申请号：US14956620

申请日：2015-12-02

Applicant: Macau University of Science and Technology

Inventor： Xiao Jun Yao ,  Lai Han Leung ,  Lian Xiang Luo ,  Liang Liu

IPC: A01N43/42 ,  A61K31/444 ,  A61K31/4745

CPC classification number: A61K31/4745

Abstract: A compound suitable for treating cancer, in particular NSCLC, inhibits activity of oncogenic ROS1 kinase and ALK kinase. The compound has certain structural components such as a quinoline moiety in the backbone and at least one phenyl-containing moiety in a side chain with a hydrophobic substituent attached to the backbone via an up to 6-membered linking group as well as a further hydrophobic moiety. The presence of the structural components allows for an advantageous interaction with the ROS1 kinase domain and, further, with the ALK kinase domain. Hence, said compound represents a highly promising opportunity for patients bearing ROS1- or ALK-dependent cancer. A composition, in particular a pharmaceutical composition, includes the compound. A method for targeting cancer cells harboring an abnormality in ROS1 gene or ALK gene includes contacting a cell with the compound.

公开(公告)号：US20170079972A1

公开(公告)日：2017-03-23

申请号：US14927825

申请日：2015-10-30

Applicant: Macau University of Science and Technology

Inventor： Xiao Jun Yao ,  Lai Han Leung ,  Lian Xiang Luo ,  Liang Liu

IPC: A61K31/4743

CPC classification number: A61K31/4743

Abstract: The administration of a compound advantageously efficacious as ROS1 inhibitor and its effect on subjects with cancer includes administering a compound having certain structural components such as a quinoline moiety in the backbone and at least one tertiary amine containing moiety in a side chain as well as heteroatoms, in particular oxygen atoms, present in the backbone and the side chain for treating a subject suffering from a disease such as cancer. The presence of such structural components allows for an advantageous interaction with the ROS1 kinase domain, in particular with the hinge region. The administered compounds represent a highly promising opportunity in particular for patients bearing ROS1-dependent cancer. A method for targeting tumor cells harboring an abnormality in ROS1 gene includes contacting a cell with compounds of the present invention as well as pharmaceutical compositions comprising such compounds.

公开(公告)号：US20160367547A1

公开(公告)日：2016-12-22

申请号：US14956620

申请日：2015-12-02

Applicant: Macau University of Science and Technology

Inventor： Xiao Jun Yao ,  Lai Han Leung ,  Lian Xiang Luo ,  Liang Liu

IPC: A61K31/4745

CPC classification number: A61K31/4745

Abstract: A compound suitable for treating cancer, in particular NSCLC, inhibits activity of oncogenic ROS1 kinase and ALK kinase. The compound has certain structural components such as a quinoline moiety in the backbone and at least one phenyl-containing moiety in a side chain with a hydrophobic substituent attached to the backbone via an up to 6-membered linking group as well as a further hydrophobic moiety. The presence of the structural components allows for an advantageous interaction with the ROS1 kinase domain and, further, with the ALK kinase domain. Hence, said compound represents a highly promising opportunity for patients bearing ROS1- or ALK-dependent cancer. A composition, in particular a pharmaceutical composition, includes the compound. A method for targeting cancer cells harboring an abnormality in ROS1 gene or ALK gene includes contacting a cell with the compound.

Abstract translation: 适用于治疗癌症，特别是NSCLC的化合物抑制致癌ROS1激酶和ALK激酶的活性。 该化合物具有某些结构组分，例如骨架中的喹啉部分，以及至少一个侧链中具有疏水性取代基的至少一个含苯基的部分通过至多6元连接基团连接至骨架，以及另外的疏水部分 。 结构组分的存在允许与ROS1激酶结构域以及进一步与ALK激酶结构域的有利相互作用。 因此，所述化合物对于患有ROS1-或ALK依赖性癌症的患者是非常有希望的机会。 组合物，特别是药物组合物，包括该化合物。 用于靶向在ROS1基因或ALK基因中具有异常的癌细胞的方法包括使细胞与化合物接触。