公开(公告)号：US20210109101A1

公开(公告)日：2021-04-15

申请号：US16884737

申请日：2020-05-27

申请人： THE SCRIPPS RESEARCH INSTITUTE ,  COLD SPRING HARBOR LABORATORY

发明人： Peter Kuhn ,  Angel Ernesto Dago Rodriguez ,  Anders Carlsson ,  Wei Liu ,  Jim Hicks

IPC分类号： G01N33/574

摘要： The present invention provides methods for predicting response to a hormone-directed therapy or chemotherapy in a prostate cancer (PCa) patient comprising (a) performing a direct analysis comprising immunofluorescent staining and morphological characteristization of nucleated cells in a blood sample obtained from the patient to identify and enumerate circulating tumor cells (CTC); (b) individually characterizing genotypic, morphometric and protein expression parameters to generate a profile for each of the CTCs, and (c) predicting response to hormone-directed therapy in the prostate cancer PCa patient based on said profile. In some embodiments, the methods comprise repeating steps (a) through (c) at one or more timepoints after initial diagnosis of prostate cancer to sequentially monitor said genotypic, morphometric and protein expression parameters.

公开(公告)号：US20210109086A1

公开(公告)日：2021-04-15

申请号：US16885028

申请日：2020-05-27

申请人： The Scripps Research Institute ,  The Board of Trustees of The Leland Stanford Junior University

发明人： Peter Kuhn ,  Anders Carlsson ,  Anand Kolatkar ,  Sanjiv Sam Gambhir ,  Viswam S. Nair

IPC分类号： G01N33/50 ,  A61K51/04 ,  A61K49/00

摘要： The present invention provides methods for diagnosing lung cancer in a subject comprising (a) generating circulating tumor cell (CTC) data from a blood sample obtained from the subject based on a direct analysis comprising immunofluorescent staining and morphological characteristics of nucleated cells in the sample, wherein CTCs are identified in context of surrounding nucleated cells based on a combination of the immunofluorescent staining and morphological characteristics; (b) obtaining clinical data for the subject; (c) combining the CTC data with the clinical data to diagnose lung cancer in the subject.

公开(公告)号：US20210094969A1

公开(公告)日：2021-04-01

申请号：US16949983

申请日：2020-11-23

申请人： The Scripps Research Institute

发明人： Thomas D, Bannister ,  William R. Roush ,  John L. Cleveland ,  Jun Yong Choi ,  Reji N. Nair ,  Andy S. Tsai ,  Jitendra K. Mishra

IPC分类号： C07D495/04 ,  A61K31/519 ,  C07D487/04 ,  A61K31/155 ,  A61K31/5025

摘要： The invention provides compounds of formulae A, B, and C as described herein that inhibit monocarboxylate transporters, such as MCT1 and MCT4. Compounds of the invention can be used for treatment of a condition in a patient, wherein the condition is characterized by the heightened activity or by the high prevalence of MCT1 and/or MCT4, such as cancer or type II diabetes.

公开(公告)号：US20210061784A1

公开(公告)日：2021-03-04

申请号：US16998963

申请日：2020-08-20

申请人： The Scripps Research Institute ,  Universität Bremen

发明人： Hank Michael James PETRASSI ,  Murali Mohan Reddy PERAM SURAKATTULA ,  Kathrin MAEDLER ,  Amin ARDESTANI ,  Jason T. ROLAND ,  Tyler D. BAGULEY ,  Matthew S. TREMBLAY ,  Weijun SHEN ,  Peter G. SCHULTZ ,  Arnab K. CHATTERJEE

IPC分类号： C07D401/12 ,  A61K31/47 ,  C12N9/12 ,  A61K31/517 ,  A61K31/4709 ,  C07D215/44 ,  C07D215/46 ,  C07D413/12 ,  C07D471/04 ,  C07D491/052 ,  C07D491/056

摘要： Disclosed herein are compounds, compositions, and methods of their use for the treatment of diabetes.

公开(公告)号：US10859585B2

公开(公告)日：2020-12-08

申请号：US16235096

申请日：2018-12-28

申请人： THE SCRIPPS RESEARCH INSTITUTE

发明人： Benjamin F. Cravatt ,  Micah J. Niphakis ,  Kenneth Lum ,  Bruno Correia ,  Armand Cognetta ,  Jonathan Hulce

IPC分类号： G01N33/92 ,  G01N33/68

摘要： Disclosed herein are methods, compositions, probes, assays and kits for identifying a lipid binding protein as a drug binding target. Also disclosed herein are methods, compositions, and probes for mapping a ligand binding site on a lipid binding protein, identification of lipid binding proteins, generating drug-lipid binding protein profiles, high throughput drug screening, and identification of drugs as potential lipid binding protein ligands.

公开(公告)号：US10782295B2

公开(公告)日：2020-09-22

申请号：US14911316

申请日：2014-08-13

申请人： THE SCRIPPS RESEARCH INSTITUTE

发明人： Benjamin Cravatt ,  Chu Wang ,  Keriann Backus

IPC分类号： G01N33/573 ,  C12N9/12 ,  C40B30/00 ,  G01N33/68

摘要： Cells produce electrophilic products with the potential to modify and affect the function of proteins. Chemoproteomic methods have provided a means to qualitatively inventory proteins targeted by endogenous electrophiles; however, ascertaining the potency and specificity of these reactions to identify the most sensitive sites in the proteome to electrophilic modification requires more quantitative methods. Here, we describe a competitive activity-based profiling method for quantifying the reactivity of electrophilic compounds against 1000+ cysteines in parallel in the human proteome. Using this approach, we identify a select set of proteins that constitute hot spots for modification by various lipid-derived electrophiles, including the oxidative stress product 4-hydroxnonenal (HNE). We show that one of these proteins, ZAK kinase, is labeled by HNE on a conserved, active site-proximal cysteine, resulting in enzyme inhibition to create a negative feedback mechanism that can suppress the activation of JNK pathways by oxidative stress.

公开(公告)号：US20200283440A1

公开(公告)日：2020-09-10

申请号：US16848032

申请日：2020-04-14

申请人： THE SCRIPPS RESEARCH INSTITUTE

发明人： Kim D. JANDA ,  Nicholas T. JACOB ,  Jonathan W. LOCKNER

IPC分类号： C07D471/14 ,  A61K31/519

摘要： There are disclosed imidazolinopyrimidinone compounds that have activity to induce TRAIL gene expression in macrophages. There is further disclosed a method for treating various cancers comprising administering effective amounts of an imidazolinopyrimidinone having the structure of Formula I herein.

公开(公告)号：US10759743B2

公开(公告)日：2020-09-01

申请号：US16344092

申请日：2017-10-19

申请人： The Scripps Research Institute

发明人： Jin-Quan Yu

IPC分类号： C07C211/35 ,  C07C211/03 ,  C07C269/04 ,  C07D215/12 ,  C07C209/68 ,  C07D213/40 ,  C07D213/61 ,  C07B37/04 ,  B01J31/22 ,  C07D213/64 ,  C07D241/42 ,  C07D319/18 ,  C07D333/22 ,  C07D471/04

摘要： Pd(II)-catalyzed g-G(sp3)-H arylation or heteroarylation of primary amines is realized by using 2-hydroxynicotinaldehyde as a catalytic transient directing group. Importantly, the catalyst and the directing group loading can be lowered to 2% and 4% respectively, thus demonstrating high efficiency of this newly designed transient directing group. Heterocyclic aryl iodides are also compatible with this reaction. Furthermore, swift synthesis of 1,2,3,4-tetrahydronaphthyridine derivatives is accomplished using this reaction.

公开(公告)号：US20200268683A1

公开(公告)日：2020-08-27

申请号：US16871902

申请日：2020-05-11

申请人： THE SCRIPPS RESEARCH INSTITUTE

发明人： Jie LI ,  Zilei LIU ,  Suhua LI ,  Peng WU ,  K. Barry SHARPLESS

IPC分类号： A61K31/05 ,  A61K31/136 ,  C07C305/26 ,  C07K1/113 ,  C07K1/02 ,  A61K51/04 ,  A61K38/31 ,  A61K31/7048 ,  A61K31/70 ,  A61K31/655 ,  A61K31/65 ,  A61K31/56 ,  A61K31/5513 ,  A61K31/53 ,  A61K31/515 ,  A61K31/505 ,  A61K31/485 ,  A61K31/4745 ,  A61K31/473 ,  A61K31/4709 ,  A61K31/47 ,  A61K31/439 ,  A61K31/4353 ,  A61K31/4245 ,  A61K31/4168 ,  A61K31/407 ,  A61K31/4045 ,  A61K31/40 ,  A61K31/397 ,  A61K31/198 ,  A61K31/197 ,  A61K31/14 ,  C07K2/00 ,  C07D295/26 ,  C07D295/185 ,  C07D295/088 ,  C07D277/82 ,  A61K47/54

摘要： A high-throughput screening methods for identifying candidate anticancer medicinal agents is described herein. The candidate anticancer medicinal agents are arylfluorosulfate compounds derived from phenolic compounds. The method involves in situ generation of the arylfluorosulfate compounds in multi-well plates by reaction of phenolic compounds in DMSO with a saturated solution of SO2F2 dissolved in a solvent such as acetonitrile, in the presence of an organic base, followed by reaction of generated fluoride ion with trimethylsilyl chloride to form volatile trimethylsilyl fluoride. Solvents, organic base, and silyl compounds are then removed, in vacuo, to afford the arylfluorosulfate compounds suitable for biological screening in cancer cell lines without further purification.

公开(公告)号：US10745340B2

公开(公告)日：2020-08-18

申请号：US14770039

申请日：2014-02-25

申请人： The Scripps Research Institute

发明人： Roy A Periana ,  Brian G Hashiguchi ,  Michael M Konnick ,  Steven M Bischof

IPC分类号： C07C67/035

摘要： The invention provides processes and materials for the efficient and cost-effective functionalization of alkanes, such as methane from natural gas, to provide esters, alcohols, and other compounds. The method can be used to produce liquid fuels such as methanol from a natural gas methane-containing feedstock. The soft oxidizing electrophile, a compound of a main group, post-transitional element such as Tl, Pb, Bi, and I, that reacts to activate the alkane C—H bond can be regenerated using inexpensive regenerants such as hydrogen peroxide, oxygen, halogens, nitric acid, etc. Main group compounds useful for carrying out this reaction includes haloacetate salts of metals having a pair of available oxidation states, such as Tl, Pb, Bi, and I. The inventors herein believe that a unifying feature of many of the MXn electrophiles useful in carrying out this reaction, such as Tl, Pb, and Bi species, is their isoelectronic configuration in the alkane-reactive oxidation state; the electrons having the configuration [Xe]4f145d10, with an empty 6s orbital. However, the iodine reagents have a different electronic configuration.