Evidence map›Paper›PMID 35644882›Full record

ArticleChemMedChem2022

Discovery and Characterization of Multiple Classes of Human CatSper Blockers.

Erick J Carlson, Rawle Francis, Yutong Liu, Ping Li, Maximilian Lyon, Celia M Santi, Derek J Hook, Jon E Hawkinson, Gunda I Georg

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

Article in ChemMedChem, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
4.6field-weighted citation impact, top 5% 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

21 citing papers in PubMed, 27 citations in OpenAlex.

  1. Article
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  9. Review
  10. The uniqueness of on-demand male contraception.Molecular aspects of medicine · 2024
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Erick J CarlsonDepartment of Medicinal Chemistry and, Institute for Therapeutics Discovery and Development, College of Pharmacy, University of Minnesota, 717 Delaware Street, SE, Minneapolis, MN 55414, USA.ORCID 0000-0003-0288-384X
Rawle FrancisDepartment of Medicinal Chemistry and, Institute for Therapeutics Discovery and Development, College of Pharmacy, University of Minnesota, 717 Delaware Street, SE, Minneapolis, MN 55414, USA.ORCID 0000-0001-9278-8760
Yutong LiuDepartment of Medicinal Chemistry and, Institute for Therapeutics Discovery and Development, College of Pharmacy, University of Minnesota, 717 Delaware Street, SE, Minneapolis, MN 55414, USA.ORCID 0000-0001-5432-683X
Ping LiDepartment of Obstetrics and Gynecology, Washington University School of Medicine, 425 S. Euclid Avenue, St. Louis, MO 63110, USA.ORCID 0000-0001-6302-4470
Maximilian LyonDepartment of Obstetrics and Gynecology, Washington University School of Medicine, 425 S. Euclid Avenue, St. Louis, MO 63110, USA.ORCID 0000-0002-2930-1726
Celia M SantiDepartment of Obstetrics and Gynecology, Washington University School of Medicine, 425 S. Euclid Avenue, St. Louis, MO 63110, USA.ORCID 0000-0002-5101-1303
Derek J HookDepartment of Medicinal Chemistry and, Institute for Therapeutics Discovery and Development, College of Pharmacy, University of Minnesota, 717 Delaware Street, SE, Minneapolis, MN 55414, USA.ORCID 0000-0001-8122-8493
Jon E HawkinsonDepartment of Medicinal Chemistry and, Institute for Therapeutics Discovery and Development, College of Pharmacy, University of Minnesota, 717 Delaware Street, SE, Minneapolis, MN 55414, USA.ORCID 0000-0001-5461-7071
Gunda I GeorgDepartment of Medicinal Chemistry and, Institute for Therapeutics Discovery and Development, College of Pharmacy, University of Minnesota, 717 Delaware Street, SE, Minneapolis, MN 55414, USA.ORCID 0000-0002-8900-9460
University of Minnesota · USWashington University in St. Louis · US

Funding

Drug Discovery & Synthesis of Contraceptive AgentsU01HD076542 · NICHD · UNIVERSITY OF MINNESOTA · PI GEORG, GUNDA I. · 2012 to 2016
$5.0M
SLO3 KO MOUSE: A TOOL TO REVEAL VOLTAGE-DEPENDENT PROCESSES IN SPERM FERTILITYR01HD069631 · NICHD · WASHINGTON UNIVERSITY · PI SANTI, CELIA M · 2011 to 2022
$3.3M
Developing modulators of the sperm-specific potassium channel SLO3 for contraceptionR33HD099742 · NICHD · WASHINGTON UNIVERSITY · PI DENTON, JEROD S., SANTI, CELIA M · 2021 to 2023
$2.1M
NICHD NIH HHS R01 HD069631NICHD NIH HHS R33 HD099742NICHD NIH HHS U01 HD076542
6 · The paper itself

Abstract

The cation channel of sperm (CatSper) is a validated target for nonhormonal male contraception, but it lacks selective blockers, hindering studies to establish its role in both motility and capacitation. Via an innovative calcium uptake assay utilizing human sperm we discovered novel inhibitors of CatSper function from a high-throughput screening campaign of 72,000 compounds. Preliminary SAR was established for seven hit series. HTS hits or their more potent analogs blocked potassium-induced depolarization and noncompetitively inhibited progesterone-induced CatSper activation. CatSper channel blockade was confirmed by patch clamp electrophysiology and these compounds inhibited progesterone- and prostaglandin E1-induced hyperactivated sperm motility. One of the hit compounds is a potent CatSper inhibitor with high selectivity for CatSper over hCav1.2, hNav1.5, moderate selectivity over hSlo3 and hERG, and low cytotoxicity and is therefore the most promising inhibitor identified in this study. These new CatSper blockers serve as useful starting points for chemical probe development and drug discovery efforts.

Indexed as

Calcium ChannelsSperm MotilityCalciumCalcium SignalingHumansMaleProgesteroneSemenSpermatozoaCalciumCalcium ChannelsProgesteronecation channel of spermelectrophysiologyinhibitorsselectivitysperm motility

Identifiers

PMID35644882
PMCPMC9378630
OpenAlexW4281732969

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.