Evidence map›Paper›PMID 27437080›Full record

ArticleACS medicinal chemistry letters2016

Discovery of MK-7145, an Oral Small Molecule ROMK Inhibitor for the Treatment of Hypertension and Heart Failure.

Haifeng Tang, Yuping Zhu, Nardos Teumelsan, Shawn P Walsh, Aurash Shahripour, Birgit T Priest, Andrew M Swensen, John P Felix, Richard M Brochu, Timothy Bailey and 17 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in ACS medicinal chemistry letters, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
2.3field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 34 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Emerging Targets of Diuretic Therapy.Clinical pharmacology and therapeutics · 2017
    Review
  6. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

27 authors at 1 institution in 1 country.

Haifeng TangDepartments of Discovery Chemistry, Ion Channels, In Vivo Pharmacology, Cardiorenal, and Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
Yuping ZhuDepartments of Discovery Chemistry, Ion Channels, In Vivo Pharmacology, Cardiorenal, and Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
Nardos TeumelsanDepartments of Discovery Chemistry, Ion Channels, In Vivo Pharmacology, Cardiorenal, and Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
Shawn P WalshDepartments of Discovery Chemistry, Ion Channels, In Vivo Pharmacology, Cardiorenal, and Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
Aurash ShahripourDepartments of Discovery Chemistry, Ion Channels, In Vivo Pharmacology, Cardiorenal, and Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
Birgit T PriestDepartments of Discovery Chemistry, Ion Channels, In Vivo Pharmacology, Cardiorenal, and Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
Andrew M SwensenDepartments of Discovery Chemistry, Ion Channels, In Vivo Pharmacology, Cardiorenal, and Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
John P FelixDepartments of Discovery Chemistry, Ion Channels, In Vivo Pharmacology, Cardiorenal, and Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
Richard M BrochuDepartments of Discovery Chemistry, Ion Channels, In Vivo Pharmacology, Cardiorenal, and Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
Timothy BaileyDepartments of Discovery Chemistry, Ion Channels, In Vivo Pharmacology, Cardiorenal, and Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
Brande Thomas-FowlkesDepartments of Discovery Chemistry, Ion Channels, In Vivo Pharmacology, Cardiorenal, and Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
Lee-Yuh PaiDepartments of Discovery Chemistry, Ion Channels, In Vivo Pharmacology, Cardiorenal, and Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
Caryn HamptonDepartments of Discovery Chemistry, Ion Channels, In Vivo Pharmacology, Cardiorenal, and Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
Aaron CoronaDepartments of Discovery Chemistry, Ion Channels, In Vivo Pharmacology, Cardiorenal, and Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
Melba HernandezDepartments of Discovery Chemistry, Ion Channels, In Vivo Pharmacology, Cardiorenal, and Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
Joseph MetzgerDepartments of Discovery Chemistry, Ion Channels, In Vivo Pharmacology, Cardiorenal, and Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
Michael ForrestDepartments of Discovery Chemistry, Ion Channels, In Vivo Pharmacology, Cardiorenal, and Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
Xiaoyan ZhouDepartments of Discovery Chemistry, Ion Channels, In Vivo Pharmacology, Cardiorenal, and Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
Karen OwensDepartments of Discovery Chemistry, Ion Channels, In Vivo Pharmacology, Cardiorenal, and Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
Vincent TongDepartments of Discovery Chemistry, Ion Channels, In Vivo Pharmacology, Cardiorenal, and Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
Emma ParmeeDepartments of Discovery Chemistry, Ion Channels, In Vivo Pharmacology, Cardiorenal, and Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
Sophie RoyDepartments of Discovery Chemistry, Ion Channels, In Vivo Pharmacology, Cardiorenal, and Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
Gregory J KaczorowskiDepartments of Discovery Chemistry, Ion Channels, In Vivo Pharmacology, Cardiorenal, and Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
Lihu YangDepartments of Discovery Chemistry, Ion Channels, In Vivo Pharmacology, Cardiorenal, and Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
Magdalena Alonso-GaliciaDepartments of Discovery Chemistry, Ion Channels, In Vivo Pharmacology, Cardiorenal, and Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
Maria L GarciaDepartments of Discovery Chemistry, Ion Channels, In Vivo Pharmacology, Cardiorenal, and Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
Alexander PasternakDepartments of Discovery Chemistry, Ion Channels, In Vivo Pharmacology, Cardiorenal, and Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
Merck & Co., Inc., Rahway, NJ, USA (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

ROMK, the renal outer medullary potassium channel, is involved in potassium recycling at the thick ascending loop of Henle and potassium secretion at the cortical collecting duct in the kidney nephron. Because of this dual site of action, selective inhibitors of ROMK are expected to represent a new class of diuretics/natriuretics with superior efficacy and reduced urinary loss of potassium compared to standard-of-care loop and thiazide diuretics. Following our earlier work, this communication will detail subsequent medicinal chemistry endeavors to further improve lead selectivity against the hERG channel and preclinical pharmacokinetic properties. Pharmacological assessment of highlighted inhibitors will be described, including pharmacodynamic studies in both an acute rat diuresis/natriuresis model and a subchronic blood pressure model in spontaneous hypertensive rats. These proof-of-biology studies established for the first time that the human and rodent genetics accurately predict the in vivo pharmacology of ROMK inhibitors and supported identification of the first small molecule ROMK inhibitor clinical candidate, MK-7145.

Indexed as

diureticsheart failurehypertensionMK-7145natriuresisROMK

Identifiers

PMID27437080
PMCPMC4948008
OpenAlexW2388612265

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.