Screening through Lead Optimization of High Affinity, Allosteric Cyclin-Dependent Kinase 2 (CDK2) Inhibitors as Male Contraceptives That Reduce Sperm Counts in Mice.
Article in Journal of medicinal chemistry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
6.7field-weighted citation impact, top 3% 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
12 citing papers in PubMed, 29 citations in OpenAlex.
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
17 authors at 2 institutions in 1 country.
Erik B FaberDepartment of Medicinal Chemistry and Institute for Therapeutics Discovery and Development, University of Minnesota College of Pharmacy─Twin Cities, Minneapolis, Minnesota55414, United States.ORCID 0000-0002-0525-3774
Nan WangDepartment of Medicinal Chemistry and Institute for Therapeutics Discovery and Development, University of Minnesota College of Pharmacy─Twin Cities, Minneapolis, Minnesota55414, United States.ORCID 0000-0002-7869-3797
Kristen JohnDepartment of Medicinal Chemistry and Institute for Therapeutics Discovery and Development, University of Minnesota College of Pharmacy─Twin Cities, Minneapolis, Minnesota55414, United States.ORCID 0000-0002-9981-6100
Luxin SunDrug Discovery Department, Moffitt Cancer Center, Tampa, Florida33612, United States.ORCID 0000-0001-5260-4664
Henry L WongDepartment of Medicinal Chemistry and Institute for Therapeutics Discovery and Development, University of Minnesota College of Pharmacy─Twin Cities, Minneapolis, Minnesota55414, United States.ORCID 0000-0003-1755-1485
David BurbanDepartment of Pharmacology, University of Minnesota Medical School─Twin Cities, Minneapolis, Minnesota55455, United States.ORCID 0000-0003-1930-2992
Rawle FrancisDepartment of Medicinal Chemistry and Institute for Therapeutics Discovery and Development, University of Minnesota College of Pharmacy─Twin Cities, Minneapolis, Minnesota55414, United States.
Defeng TianDepartment of Medicinal Chemistry and Institute for Therapeutics Discovery and Development, University of Minnesota College of Pharmacy─Twin Cities, Minneapolis, Minnesota55414, United States.ORCID 0000-0002-3900-2324
Kwon H HongDepartment of Medicinal Chemistry and Institute for Therapeutics Discovery and Development, University of Minnesota College of Pharmacy─Twin Cities, Minneapolis, Minnesota55414, United States.
An YangDepartment of Medicinal Chemistry and Institute for Therapeutics Discovery and Development, University of Minnesota College of Pharmacy─Twin Cities, Minneapolis, Minnesota55414, United States.
Liming WangDepartment of Medicinal Chemistry and Institute for Therapeutics Discovery and Development, University of Minnesota College of Pharmacy─Twin Cities, Minneapolis, Minnesota55414, United States.ORCID 0000-0002-2269-5355
Mazen ElsaidDepartment of Medicinal Chemistry and Institute for Therapeutics Discovery and Development, University of Minnesota College of Pharmacy─Twin Cities, Minneapolis, Minnesota55414, United States.
Hira KhalidDepartment of Medicinal Chemistry and Institute for Therapeutics Discovery and Development, University of Minnesota College of Pharmacy─Twin Cities, Minneapolis, Minnesota55414, United States.
Nicholas M LevinsonDepartment of Pharmacology, University of Minnesota Medical School─Twin Cities, Minneapolis, Minnesota55455, United States.ORCID 0000-0003-4338-8087
Ernst SchönbrunnDrug Discovery Department, Moffitt Cancer Center, Tampa, Florida33612, United States.ORCID 0000-0002-3589-3510
Jon E HawkinsonDepartment of Medicinal Chemistry and Institute for Therapeutics Discovery and Development, University of Minnesota College of Pharmacy─Twin Cities, Minneapolis, Minnesota55414, United States.ORCID 0000-0001-5461-7071
Gunda I GeorgDepartment of Medicinal Chemistry and Institute for Therapeutics Discovery and Development, University of Minnesota College of Pharmacy─Twin Cities, Minneapolis, Minnesota55414, United States.ORCID 0000-0002-8900-9460
University of Minnesota · USMoffitt Cancer Center · US
Funding
TRANSLATIONAL RESEARCHP30CA076292 · NCI · UNIVERSITY OF SOUTH FLORIDA · PI Christine O'Connell · 1998 to 2026
$93.5M
User Training & OutreachP30GM138396 · NIGMS · UCHICAGO ARGONNE, LLC · PI JANET L. SMITH · 2020 to 2026
$34.3M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM008244 · NIGMS · UNIVERSITY OF MINNESOTA TWIN CITIES · PI SHIMIZU, YOJI · 1988 to 2024
$13.6M
Training the Next Generation of Chemical BiologistsT32GM132029 · NIGMS · UNIVERSITY OF MINNESOTA · PI Erin Elizabeth Carlson, William Charles Krause Pomerantz · 2019 to 2026
$2.7M
High-Speed High-Sensitivity Detector for X-ray Micro-Crystallography at GM/CA@APSS10OD012289 · OD · UNIVERSITY OF CHICAGO · PI FISCHETTI, ROBERT F. · 2014 to 2014
$2.0M
Decoding the dynamic mechanism of allosteric activation in the cyclin-dependent kinase Cdk2R01GM121515 · NIGMS · UNIVERSITY OF MINNESOTA · PI LEVINSON, NICHOLAS MARK · 2018 to 2022
$1.5M
Allosteric CDK2 inhibitor Discovery and Development for Male ContraceptionR61HD099743 · NICHD · UNIVERSITY OF MINNESOTA · PI CHENNATHUKUZHI, VARGHEESE MANI, GEORG, GUNDA I. · 2019 to 2020
$780k
Cell-cycle regulatory kinases as targets for male contraceptive drug developmentR01HD080431 · NICHD · UNIVERSITY OF KANSAS MEDICAL CENTER · PI CHENNATHUKUZHI, VARGHEESE MANI · 2017 to 2018
$605k
Development of Allosteric Inhibitors against Cyclin-Dependent Kinase 2 (Cdk2)F30CA232303 · NCI · UNIVERSITY OF MINNESOTA · PI FABER, ERIK · 2019 to 2021
Although cyclin-dependent kinase 2 (CDK2) is a validated target for both cancer and contraception, developing a CDK2 inhibitor with exquisite selectivity has been challenging due to the structural similarity of the ATP-binding site, where most kinase inhibitors bind. We previously discovered an allosteric pocket in CDK2 with the potential to bind a selective compound and then discovered and structurally confirmed an anthranilic acid scaffold that binds this pocket with high affinity. These allosteric inhibitors are selective for CDK2 over structurally similar CDK1 and show contraceptive potential. Herein, we describe the screening and optimization that led to compounds like
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.
Screening through Lead Optimization of High Affinity, Allosteric Cyclin-Dependent Kinase 2 (CDK2) Inhibitors as Male Contraceptives That Reduce Sperm Counts in Mice. · full record | OpenQuestion