Quinoline and thiazolopyridine allosteric inhibitors of MALT1

David A. Scott; John M. Hatcher; Hongyan Liu; Mingpeng Fu; Guangyan Du; Lorena Fontán; Ilkay Us; Gabriella Casalena; Qi Qiao; Hao Wu; Ari Melnick; Nathanael S. Gray

doi:10.1016/j.bmcl.2019.05.040

Quinoline and thiazolopyridine allosteric inhibitors of MALT1

David A. Scott, John M. Hatcher, Hongyan Liu, Mingpeng Fu, Guangyan Du, Lorena Fontán, Ilkay Us, Gabriella Casalena, Qi Qiao, Hao Wu, Ari Melnick, Nathanael S. Gray

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

Quinolines and thiazolopyridines were developed as allosteric inhibitors of MALT1, with good cellular potency and exquisite selectivity. Mouse pharmacokinetic (PK) profiling showed these to have low in vivo clearance, and moderate oral exposure. The thiazolopyridines were less lipophilic than the quinolines, and one thiazolopyridine example was active in our hIL10 mouse pharmacodynamic (PD) model upon oral dosing.

Original language	English (US)
Pages (from-to)	1694-1698
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	29
Issue number	14
DOIs	https://doi.org/10.1016/j.bmcl.2019.05.040
State	Published - Jul 15 2019
Externally published	Yes

Keywords

Allosteric
B-cell lymphomas
MALT1
Protease inhibitors

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

Access to Document

10.1016/j.bmcl.2019.05.040

Cite this

@article{6973bf13d9424c43a216109d896ec50a,

title = "Quinoline and thiazolopyridine allosteric inhibitors of MALT1",

abstract = "Quinolines and thiazolopyridines were developed as allosteric inhibitors of MALT1, with good cellular potency and exquisite selectivity. Mouse pharmacokinetic (PK) profiling showed these to have low in vivo clearance, and moderate oral exposure. The thiazolopyridines were less lipophilic than the quinolines, and one thiazolopyridine example was active in our hIL10 mouse pharmacodynamic (PD) model upon oral dosing.",

keywords = "Allosteric, B-cell lymphomas, MALT1, Protease inhibitors",

author = "Scott, {David A.} and Hatcher, {John M.} and Hongyan Liu and Mingpeng Fu and Guangyan Du and Lorena Font{\'a}n and Ilkay Us and Gabriella Casalena and Qi Qiao and Hao Wu and Ari Melnick and Gray, {Nathanael S.}",

note = "Publisher Copyright: {\textcopyright} 2019 Elsevier Ltd",

year = "2019",

month = jul,

day = "15",

doi = "10.1016/j.bmcl.2019.05.040",

language = "English (US)",

volume = "29",

pages = "1694--1698",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Limited",

number = "14",

}

TY - JOUR

T1 - Quinoline and thiazolopyridine allosteric inhibitors of MALT1

AU - Scott, David A.

AU - Hatcher, John M.

AU - Liu, Hongyan

AU - Fu, Mingpeng

AU - Du, Guangyan

AU - Fontán, Lorena

AU - Us, Ilkay

AU - Casalena, Gabriella

AU - Qiao, Qi

AU - Wu, Hao

AU - Melnick, Ari

AU - Gray, Nathanael S.

PY - 2019/7/15

Y1 - 2019/7/15

N2 - Quinolines and thiazolopyridines were developed as allosteric inhibitors of MALT1, with good cellular potency and exquisite selectivity. Mouse pharmacokinetic (PK) profiling showed these to have low in vivo clearance, and moderate oral exposure. The thiazolopyridines were less lipophilic than the quinolines, and one thiazolopyridine example was active in our hIL10 mouse pharmacodynamic (PD) model upon oral dosing.

AB - Quinolines and thiazolopyridines were developed as allosteric inhibitors of MALT1, with good cellular potency and exquisite selectivity. Mouse pharmacokinetic (PK) profiling showed these to have low in vivo clearance, and moderate oral exposure. The thiazolopyridines were less lipophilic than the quinolines, and one thiazolopyridine example was active in our hIL10 mouse pharmacodynamic (PD) model upon oral dosing.

KW - Allosteric

KW - B-cell lymphomas

KW - MALT1

KW - Protease inhibitors

UR - http://www.scopus.com/inward/record.url?scp=85065918928&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85065918928&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2019.05.040

DO - 10.1016/j.bmcl.2019.05.040

M3 - Article

C2 - 31129051

AN - SCOPUS:85065918928

SN - 0960-894X

VL - 29

SP - 1694

EP - 1698

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 14

ER -

Quinoline and thiazolopyridine allosteric inhibitors of MALT1

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this