公开(公告)号：US20240190866A1

公开(公告)日：2024-06-13

申请号：US18282219

申请日：2022-03-11

Applicant: Academia Sinica

Inventor： Wei-Chieh CHENG ,  Wei-An CHEN ,  Yu-Hsin CHEN ,  Ting-Jen CHENG ,  Chia-Ning SHEN ,  Chiao-Yun HSIEH ,  Pi-Fang HUNG

IPC: C07D471/04 ,  A61K31/437 ,  A61P35/00

CPC classification number: C07D471/04 ,  A61K31/437 ,  A61P35/00

Abstract: Disclosed herein are novel polyhydroxylated indolizidine and pyrrolizidine derivates and methods for using the same in the treatment of cancer. The present polyhydroxylated indolizidine and pyrrolizidine derivates has the structure of formula (I),




wherein: X is O or b and c are independently an integral of 0 or and 1; R is selected from the group consisting of H, C1-6 alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, aralkyl, aralkenyl, aralkynyl, heteroaralkyl, heteroaralkenyl, beteroaralkynyl, heterocyclyl, alkoxy, aryloxy, and sulfonyl.

公开(公告)号：US20220273615A1

公开(公告)日：2022-09-01

申请号：US17630929

申请日：2020-09-30

Applicant: Academia Sinica

Inventor： Wei-Chieh CHENG ,  Huang-Yi LI ,  Wuh-Liang HWU ,  Yin-Hsiu CHIEN ,  Ni-Chung LEE

IPC: A61K31/40 ,  A61K38/47 ,  A61P3/08

Abstract: Disclosed herein are novel uses of ADMDP stereoisomers or their derivatives for the manufacture of a medicament for treating Pompe disease. Accordingly, the present disclosure provides a method of treating Pompe disease in a subject. The method includes the step of, administering to the subject a therapeutically effective amount of a compound of formula (I), or a salt, an ester or a solvate thereof, wherein R1 and R2 are independently H or alkyl optionally substituted by —NH2 or —OH, so as to ameliorate, alleviate mitigate and/or prevent symptoms associated with the Pompe disease. According to certain embodiments of the present disclosure, the compound of formula (I) may serve a stabilizer of α-glucosidase via preventing its denaturalization of deactivation.

公开(公告)号：US20150232417A1

公开(公告)日：2015-08-20

申请号：US14188678

申请日：2014-02-24

Applicant: ACADEMIA SINICA

Inventor： Chi-Huey WONG ,  Che Alex MA ,  Ting-Jen Rachel CHENG ,  Wei-Chieh CHENG

IPC: C07C235/64 ,  G01N33/573

CPC classification number: C07C235/64 ,  C07C235/84 ,  C07K2299/00 ,  C12Q1/18 ,  C12Q1/48 ,  G01N33/573 ,  G01N2333/91102 ,  G01N2500/00 ,  G01N2500/04 ,  G01N2500/20

Abstract: Crystal structure at 2.16 Å resolution of full-length Escherichia coli penicillin-binding protein 1b (PBP1b) in complex with its inhibitor moenomycin, is provided. 3D structures of amino acid residues involved in moenomycin binding and transglycosylation activity are identified. Binding sites for peptidoglycan synthesis inhibitors comprising amino acid residues from transglycosylase (TG), UvrB domain 2 homolog (UB2H) and transmembrane (TM) domains of PBP1b are identified at atomic level resolution. Rational drug design, based on the atomic coordinates, are disclosed. Methods for screening for antibiotics using anisotropic binding and transglycosylase inhibitor assays and novel antibiotics based on the screening assays are provided.

Abstract translation: 提供了全长大肠杆菌青霉素结合蛋白1b（PBP1b）与其抑制剂新霉素复合物的分辨率为2.16Å的晶体结构。 鉴定涉及霉酚霉素结合和转糖基化活性的氨基酸残基的3D结构。 在原子级分辨率下鉴定了包含来自转糖苷酶（TG），UvrB结构域2同源物（UB2H）和PBP1b跨膜（TM）结构域的氨基酸残基的肽聚糖合成抑制剂的结合位点。 公开了基于原子坐标的合理药物设计。 提供了使用各向异性结合和转糖苷酶抑制剂测定法筛选抗生素的方法以及基于筛选试验的新型抗生素。

公开(公告)号：US20190225579A1

公开(公告)日：2019-07-25

申请号：US16313057

申请日：2017-06-14

Applicant: Academia Sinica

Inventor： Wei-Chieh CHENG

IPC: C07D207/02 ,  A61P3/00 ,  A61K31/7028 ,  A61K38/47

Abstract: Disclosed herein are novel uses of a polyhydroxylated pyrrolidine for the manufacture of a medicament for treating Fabry disease (FD). Accordingly, the present disclosure provides a method of treating a subject having or suspected of having FD. The method includes the step of, administering to the subject a therapeutically effective amount of a compound of formula (I), a salt, an ester or a solvate thereof, wherein: R1 is H, or C1-3 amine optionally substituted with —COR2; R2 is alkyl or alkene optionally substituted with cycloalkyl or phenyl having at least one substituent selected from the group consisting of, halo, alkyl, haloalkyl, and alkoxyl; so as to ameliorate, alleviate mitigate and/or prevent symptoms associated with the FD. According to preferred embodiments of the present disclosure, the compound of formula (I) is a chaperon of a mutated human lysosomal α-galactosidase A (α-Gal A).