Yueming Y Li

US Patent:

7196163, Mar 27, 2007

Filed:

Apr 30, 2003

Appl. No.:

10/427208

Inventors:

Daria Jean Hazuda - Doylestown PA, US
Elizabeth Chen Dodson - Souderton PA, US
Min Xu - Ambler PA, US
Xiao-Ping Shi - Warrington PA, US
Adam J. Simon - Langhorne PA, US
Guoxin Wu - Merion Station PA, US
Yueming Li - New York NY, US
Bruce Register - Berwyn PA, US

Assignee:

Merk & Co., Inc. - Rahway NJ

International Classification:

A61K 38/07
A61K 38/16

US Classification:

530330, 530350, 514 2, 514 18, 435 71, 424 9463

Abstract:

Provided are methods of identifying inhibitors of β-secretase that employ modified β-secretase substrates. The modified β-secretase substrates have β-secretase cleavage sites that are altered from wild type. The amino acid sequences of the altered β-secretase cleavage sites contain different amino acids in at least one of the positions P2-P1-P1′-P2′ of the β-secretase cleavage site. Many of the modified β-secretase substrates are more efficient substrates for β-secretase than are corresponding substrates having wild-type sequences, that is, these modified substrates are more susceptible to enzymatic breakdown by β-secretase. Recombinant polynucleotide molecules encoding the modified β-secretase substrates are provided. Antibodies that recognize cleavage products of the modified β-secretase substrates are provided. Stable cell lines expressing the modified β-secretase substrates are provided.

US Patent:

7747395, Jun 29, 2010

Filed:

Apr 13, 2007

Appl. No.:

11/787237

Inventors:

David A. Scheinberg - New York NY, US
Yehuda Goldgur - Fair Lawn NJ, US
Yueming Li - New York NY, US

Assignee:

Sloan-Kettering Institute for Cancer Research - New York NY

International Classification:

G01N 31/00
C12Q 1/34
C12Q 1/00

US Classification:

702 27, 435 18, 435 4, 435 5, 435 721, 435 722, 435 732

Abstract:

The present invention provides the three-dimensional structure of human mitochondrial peptide deformylase (HsPDF) protein, and HsPDF complexed to a binding compound, such as a PDF inhibitor. This crystallographic information will aid in the identification and development of novel binding compounds of HsPDF and other PDF family members which have anti-bacterial, anti-viral, anti-parasitical, anti-inflammatory, and/or anti-cancer activity.

US Patent:

20030215896, Nov 20, 2003

Filed:

Jan 17, 2003

Appl. No.:

10/275025

Inventors:

Yueming Li - New York NY, US
Min Xu - Ambler PA, US
Qian Huang - Orefield PA, US
Stephen Gardell - Woodbridge CT, US

International Classification:

G01N033/53
G01N033/537
G01N033/543
C12Q001/37
C07H021/04
C07K014/47
C12P021/02
C12N005/06

US Classification:

435/007920, 435/023000, 435/069100, 435/320100, 435/325000, 530/350000, 536/023200

Abstract:

The present invention features -secretase substrates and in vitro assays for measuring -secretase activity employing such substrates. The -secretase substrates described herein contain a hydrophilic polypeptide moiety covalently joined to the carboxyl terminus of a -CTF domain. A “-CTF domain” is a polypeptide that can be cleaved by -secretase and which approximates the C-terminal fragment (amino acids 596-695) of APP produced after cleavage of APP by a -secretase, or is a functional derivative thereof.

US Patent:

20060036077, Feb 16, 2006

Filed:

Oct 5, 2005

Appl. No.:

11/243578

Inventors:

Yueming Li - New York NY, US
Min Xu - Ambler PA, US
Qian Huang - Orefield PA, US
Stephen Gardell - Woodbridge CT, US

International Classification:

C07K 14/47
C12Q 1/37

US Classification:

530350000, 435023000

Abstract:

The present invention features γ-secretase substrates and in vitro assays for measuring γ-secretase activity employing such substrates. The γ-secretase substrates described herein contain a hydrophilic polypeptide moiety covalently joined to the carboxyl terminus of a β-CTF domain. A “β-CTF domain” is a polypeptide that can be cleaved by γ-secretase and which approximates the C-terminal fragment (amino acids 596-695) of APP produced after cleavage of APP by a β-secretase, or is a functional derivative thereof.

US Patent:

20070219354, Sep 20, 2007

Filed:

Mar 7, 2007

Appl. No.:

11/714985

Inventors:

Daria Hazuda - Doylestown PA, US
Elizabeth Chen Dodson - Souderton PA, US
Min Xu - Ambler PA, US
Xiao-Ping Shi - Warrington PA, US
Adam Simon - Langhorne PA, US
Guoxin Wu - Merion Station PA, US
Yueming Li - New york NY, US
Bruce Register - Berwyn PA, US

International Classification:

C07K 16/00
C07K 14/00

US Classification:

530387900, 530395000

Abstract:

Provided are methods of identifying inhibitors of β-secretase that employ modified β-secretase substrates. The modified β-secretase substrates have β-secretase cleavage sites that are altered from wild type. The amino acid sequences of the altered β-secretase cleavage sites contain different amino acids in at least one of the positions P2-P1-P1′-P2′ of the β-secretase cleavage site. Many of the modified β-secretase substrates are more efficient substrates for β-secretase than are corresponding substrates having wild-type sequences, that is, these modified substrates are more susceptible to enzymatic breakdown by β-secretase. Recombinant polynucleotide molecules encoding the modified β-secretase substrates are provided. Antibodies that recognize cleavage products of the modified β-secretase substrates are provided. Stable cell lines expressing the modified β-secretase substrates are provided. Transgenic animals expressing the modified β-secretase substrates are provided.

US Patent:

20100285988, Nov 11, 2010

Filed:

May 7, 2010

Appl. No.:

12/776141

Inventors:

Christopher Chad SHELTON - Alexandrea VA, US
Yuan TIAN - New York NY, US
Yueming LI - New York NY, US

Assignee:

MEMORIAL SLOAN-KETTERING CANCER CENTER - New York NY

International Classification:

G01N 33/573
C12Q 1/37
C12P 21/06
C12N 9/99
C12N 5/02
C40B 30/04
C07K 14/47
C07K 7/06
C07H 21/04

US Classification:

506 9, 435 74, 435 23, 435 691, 435184, 435375, 530324, 530328, 530329, 536 235

Abstract:

Polypeptide substrates based on modifications or fragments of the various APP isoforms, assay methods based on the use of these substrates, and screening methods directed toward identifying inhibitors of γ-secretase activity. The assay methods and the screening methods are adapted for use in high throughput multi-well plate assay apparatuses. In many embodiments the substrate polypeptides are labeled for ease of detection, and/or may bind specific ligands that themselves are labeled. Generally the labels promote high specificity as well as high sensitivity of detection. These features render the assay and screening methods that employ the labeled substrates especially suited for use in high throughput assay formats. This disclosure further identifies small polypeptides based on a subsequence motif of Aβ that are shown herein to be potent inhibitors of the activity of γ-secretase.

US Patent:

20160131651, May 12, 2016

Filed:

May 1, 2015

Appl. No.:

14/701581

Inventors:

- New York NY, US
Yuan Tian - New York NY, US
Yueming Li - New York NY, US

International Classification:

G01N 33/573

Abstract:

Polypeptide substrates based on modifications or fragments of the various APP isoforms, assay methods based on the use of these substrates, and screening methods directed toward identifying inhibitors of γ-secretase activity. The assay methods and the screening methods are adapted for use in high throughput multi-well plate assay apparatuses. In many embodiments the substrate polypeptides are labeled for ease of detection, and/or may bind specific ligands that themselves are labeled. Generally the labels promote high specificity as well as high sensitivity of detection. These features render the assay and screening methods that employ the labeled substrates especially suited for use in high throughput assay formats. This disclosure further identifies small polypeptides based on a subsequence motif of Aβ that are shown herein to be potent inhibitors of the activity of γ-secretase.

US Patent:

20150272962, Oct 1, 2015

Filed:

Jun 10, 2015

Appl. No.:

14/735798

Inventors:

- New York NY, US
Yueming Li - New York NY, US

International Classification:

A61K 31/5513
A61K 31/381

Abstract:

Provided are methods of treating or preventing a neurodegenerative disease comprising administering to a subject having a neurodegenerative disease an effective amount of a compound of Formula I:where X, R, R, subscript m, subscript n and subscript v are as defined herein.