Literature DB >> 22827305

Discovery and development of SQ109: a new antitubercular drug with a novel mechanism of action.

Katherine A Sacksteder1, Marina Protopopova, Clifton E Barry, Koen Andries, Carol A Nacy.   

Abstract

Existing drugs have limited efficacy against the rising threat of drug-resistant pan class="Chemical">TB, have significant side effects, and must be given in combinations of four to six drugs for at least 6 months for drug-sensitive n>n class="Chemical">TB and up to 24 months for drug-resistant TB. The long treatment duration has led to increased patient noncompliance with therapy. This, in turn, drives the development of additional drug resistance in a spiral that has resulted in some forms of TB being currently untreatable by existing drugs. New antitubercular drugs in development, particularly those with mechanisms of action that are different from existing first- and second-line TB drugs, are anticipated to be effective against both drug-sensitive and drug-resistant TB. SQ109 is a new TB drug candidate with a novel mechanism of action that was safe and well tolerated in Phase I and early Phase II clinical trials. We describe herein the identification, development and characterization of SQ109 as a promising new antitubercular drug.

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Year:  2012        PMID: 22827305      PMCID: PMC3480206          DOI: 10.2217/fmb.12.56

Source DB:  PubMed          Journal:  Future Microbiol        ISSN: 1746-0913            Impact factor:   3.165


  81 in total

1.  Ethambutol resistance in Mycobacterium tuberculosis: critical role of embB mutations.

Authors:  S Sreevatsan; K E Stockbauer; X Pan; B N Kreiswirth; S L Moghazeh; W R Jacobs; A Telenti; J M Musser
Journal:  Antimicrob Agents Chemother       Date:  1997-08       Impact factor: 5.191

2.  Preliminary observations of ethambutol in pulmonary tuberculosis.

Authors:  G DeSimoni
Journal:  Ann N Y Acad Sci       Date:  1966-04-20       Impact factor: 5.691

3.  Identification of a new antitubercular drug candidate, SQ109, from a combinatorial library of 1,2-ethylenediamines.

Authors:  Marina Protopopova; Colleen Hanrahan; Boris Nikonenko; Rowena Samala; Ping Chen; Jackie Gearhart; Leo Einck; Carol A Nacy
Journal:  J Antimicrob Chemother       Date:  2005-09-19       Impact factor: 5.790

4.  Novel linear diamine disubstituted polycyclic 'cage' derivatives as potential antimycobacterial candidates.

Authors:  Oluseye K Onajole; Sphelele Sosibo; Patrick Govender; Thavendran Govender; Paul D van Helden; Glenn E M Maguire; Kata Mlinarić-Majerski; Ian Wiid; Hendrik G Kruger
Journal:  Chem Biol Drug Des       Date:  2011-10-24       Impact factor: 2.817

Review 5.  Drugs in development for tuberculosis.

Authors:  Ann M Ginsberg
Journal:  Drugs       Date:  2010-12-03       Impact factor: 9.546

6.  SQ109 targets MmpL3, a membrane transporter of trehalose monomycolate involved in mycolic acid donation to the cell wall core of Mycobacterium tuberculosis.

Authors:  Kapil Tahlan; Regina Wilson; David B Kastrinsky; Kriti Arora; Vinod Nair; Elizabeth Fischer; S Whitney Barnes; John R Walker; David Alland; Clifton E Barry; Helena I Boshoff
Journal:  Antimicrob Agents Chemother       Date:  2012-01-17       Impact factor: 5.191

7.  The arabinosyltransferase EmbC is inhibited by ethambutol in Mycobacterium tuberculosis.

Authors:  R Goude; A G Amin; D Chatterjee; T Parish
Journal:  Antimicrob Agents Chemother       Date:  2009-07-13       Impact factor: 5.191

8.  Linezolid in the treatment of multidrug-resistant tuberculosis.

Authors:  G F Schecter; C Scott; L True; A Raftery; J Flood; S Mase
Journal:  Clin Infect Dis       Date:  2010-01-01       Impact factor: 9.079

9.  Discovery of dipiperidines as new antitubercular agents.

Authors:  Elena Bogatcheva; Colleen Hanrahan; Ping Chen; Jacqueline Gearhart; Katherine Sacksteder; Leo Einck; Carol Nacy; Marina Protopopova
Journal:  Bioorg Med Chem Lett       Date:  2009-11-04       Impact factor: 2.823

10.  Outcomes of multi-drug resistant tuberculosis (MDR-TB) among a cohort of South African patients with high HIV prevalence.

Authors:  Jason E Farley; Malathi Ram; William Pan; Stacie Waldman; Gail H Cassell; Richard E Chaisson; Karin Weyer; Joey Lancaster; Martie Van der Walt
Journal:  PLoS One       Date:  2011-07-22       Impact factor: 3.240

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  74 in total

Review 1.  Investigational antimicrobial agents of 2013.

Authors:  Michael J Pucci; Karen Bush
Journal:  Clin Microbiol Rev       Date:  2013-10       Impact factor: 26.132

2.  SQ109, a new drug lead for Chagas disease.

Authors:  Phercyles Veiga-Santos; Kai Li; Lilianne Lameira; Tecia Maria Ulisses de Carvalho; Guozhong Huang; Melina Galizzi; Na Shang; Qian Li; Dolores Gonzalez-Pacanowska; Vanessa Hernandez-Rodriguez; Gustavo Benaim; Rey-Ting Guo; Julio A Urbina; Roberto Docampo; Wanderley de Souza; Eric Oldfield
Journal:  Antimicrob Agents Chemother       Date:  2015-01-12       Impact factor: 5.191

Review 3.  The future for early-stage tuberculosis drug discovery.

Authors:  Edison S Zuniga; Julie Early; Tanya Parish
Journal:  Future Microbiol       Date:  2015       Impact factor: 3.165

4.  Spirocycle MmpL3 Inhibitors with Improved hERG and Cytotoxicity Profiles as Inhibitors of Mycobacterium tuberculosis Growth.

Authors:  Peter C Ray; Margaret Huggett; Penelope A Turner; Malcolm Taylor; Laura A T Cleghorn; Julie Early; Anuradha Kumar; Shilah A Bonnett; Lindsay Flint; Douglas Joerss; James Johnson; Aaron Korkegian; Steven Mullen; Abraham L Moure; Susan H Davis; Dinakaran Murugesan; Michael Mathieson; Nicola Caldwell; Curtis A Engelhart; Dirk Schnappinger; Ola Epemolu; Fabio Zuccotto; Jennifer Riley; Paul Scullion; Laste Stojanovski; Lisa Massoudi; Gregory T Robertson; Anne J Lenaerts; Gail Freiberg; Dale J Kempf; Thierry Masquelin; Philip A Hipskind; Joshua Odingo; Kevin D Read; Simon R Green; Paul G Wyatt; Tanya Parish
Journal:  ACS Omega       Date:  2021-01-13

5.  Screening the Pathogen Box for Identification of Candida albicans Biofilm Inhibitors.

Authors:  Taissa Vila; Jose L Lopez-Ribot
Journal:  Antimicrob Agents Chemother       Date:  2016-12-27       Impact factor: 5.191

6.  Identification of New MmpL3 Inhibitors by Untargeted and Targeted Mutant Screens Defines MmpL3 Domains with Differential Resistance.

Authors:  John T Williams; Elizabeth R Haiderer; Garry B Coulson; Kayla N Conner; Edmund Ellsworth; Chao Chen; Nadine Alvarez-Cabrera; Wei Li; Mary Jackson; Thomas Dick; Robert B Abramovitch
Journal:  Antimicrob Agents Chemother       Date:  2019-09-23       Impact factor: 5.191

7.  In vitro activity of AZD5847 against geographically diverse clinical isolates of Mycobacterium tuberculosis.

Authors:  Jim Werngren; Maria Wijkander; Nasrin Perskvist; V Balasubramanian; Vasan K Sambandamurthy; Camilla Rodrigues; Sven Hoffner
Journal:  Antimicrob Agents Chemother       Date:  2014-04-28       Impact factor: 5.191

8.  Diphenylether-Modified 1,2-Diamines with Improved Drug Properties for Development against Mycobacterium tuberculosis.

Authors:  Marie H Foss; Sovitj Pou; Patrick M Davidson; Jennifer L Dunaj; Rolf W Winter; Sovijja Pou; Meredith H Licon; Julia K Doh; Yuexin Li; Jane X Kelly; Rozalia A Dodean; Dennis R Koop; Michael K Riscoe; Georgiana E Purdy
Journal:  ACS Infect Dis       Date:  2016-05-13       Impact factor: 5.084

9.  Inhibition of Leishmania mexicana Growth by the Tuberculosis Drug SQ109.

Authors:  Verónica García-García; Eric Oldfield; Gustavo Benaim
Journal:  Antimicrob Agents Chemother       Date:  2016-09-23       Impact factor: 5.191

Review 10.  Inhibiting Mycobacterium tuberculosis within and without.

Authors:  Stewart T Cole
Journal:  Philos Trans R Soc Lond B Biol Sci       Date:  2016-11-05       Impact factor: 6.237

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