Affinage

PKMYT1

Membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase · UniProt Q99640

Length
499 aa
Mass
54.5 kDa
Annotated
2026-06-10
73 papers in source corpus 29 papers cited in narrative 29 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/8 claims corpus-supported (88%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PKMYT1 is a membrane-associated dual-specificity kinase that phosphorylates CDK1 at both Thr14 and Tyr15 to maintain CDK1/Cyclin B in its inhibitory state and restrain the G2/M transition, distinguishing it from WEE1, which phosphorylates only Tyr15 (PMID:29168755). Its kinase activities require intact protein substrates rather than peptides, indicating recognition at the protein level (PMID:22189141). In normal cells PKMYT1 acts redundantly with WEE1 to enforce mitotic timing, but this redundancy is lost in oncogenic contexts, creating selective dependencies: PKMYT1 loss is lethal in glioblastoma stem cells (PMID:26673326), and PKMYT1 kinase activity is synthetically lethal with CCNE1 amplification, where its inhibition drives unscheduled CDK1 activation and premature mitosis during DNA synthesis (PMID:35444283). This synthetic-lethal logic extends to low-molecular-weight cyclin E, which stabilizes PKMYT1 to raise CDK1 phosphorylation (PMID:39186665), to Rb1 loss combined with ATR inhibition (PMID:41442499), and to combined WEE1/PKMYT1 inhibition, all converging on replication catastrophe and DNA damage (PMID:37325550). Beyond CDK1, PKMYT1 has a distinct mitotic role: its activity rises during anaphase to safeguard chromosome segregation and spindle assembly checkpoint integrity, and its inhibition produces segregation errors that activate cGAS-STING innate immune signaling (PMID:42243523, PMID:41617394). The selective inhibitor RP-6306 exploits these dependencies, achieving selectivity over WEE1 through active-site contacts at Asp251 and Tyr121, while an allosteric chemotype engages a cryptic P-loop site (PMID:35880755, PMID:39163619, PMID:42227652). PKMYT1 also phosphorylates NPM1 at S260 to impair SUMOylation-dependent recruitment of BRCA1, RAP80, and RAD51 to double-strand breaks, linking it to DNA repair and chemoresistance (PMID:40393983). PKMYT1 is transcriptionally upregulated by E2F7, ELF3, and TEAD4 (PMID:38253021, PMID:36988891, PMID:37729973), its mRNA is stabilized via m6A reader IGF2BP3 under ALKBH5 control (PMID:35114989), and its protein level is set by opposing USP49 stabilization and TRIM25-mediated K48 ubiquitination (PMID:41443044, PMID:40279509).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2017 High

    Established PKMYT1's core biochemical identity, distinguishing it from WEE1 by its dual Thr14/Tyr15 phosphorylation of CDK1 and defining it as a G2/M-restraining kinase.

    Evidence In vitro kinase assays with Thr14/Tyr15 phospho-specific readouts

    PMID:29168755

    Open questions at the time
    • Does not address membrane targeting or substrate-recognition determinants
    • No structural basis for dual specificity provided
  2. 2011 Medium

    Showed PKMYT1 requires protein-level substrates rather than peptides, indicating that substrate context governs its catalysis and complicating peptide-based inhibitor screens.

    Evidence In vitro kinase assays comparing peptide vs protein substrates plus MD simulations

    PMID:22189141

    Open questions at the time
    • Structural basis for protein-substrate requirement not defined
    • Single lab, no independent replication noted
  3. 2015 High

    Demonstrated WEE1/PKMYT1 redundancy in normal cells is broken in tumor cells, establishing the conceptual basis for tumor-selective PKMYT1 dependency.

    Evidence Genome-wide CRISPR knockout screens in GSCs vs NSCs with CDK1-Y15 readouts and in vivo validation

    PMID:26673326

    Open questions at the time
    • Molecular cause of lost redundancy in tumor cells not fully defined
    • Limited to glioblastoma context
  4. 2022 High

    Identified CCNE1 amplification as a synthetic-lethal partner and delivered RP-6306 as a selective tool/clinical-grade inhibitor, converting PKMYT1 biology into a therapeutic strategy.

    Evidence Genome-scale CRISPR synthetic-lethality screens, structure-based inhibitor design, CDK1 phosphorylation assays, and xenografts

    PMID:35444283 PMID:35880755

    Open questions at the time
    • Full set of co-dependencies beyond CCNE1 not enumerated
    • MMB-FOXM1 contribution defined only in part
  5. 2023 Medium

    Mapped transcriptional and post-transcriptional control of PKMYT1, showing E2F7, ELF3, TEAD4 drive its expression and m6A reader IGF2BP3 stabilizes its mRNA, explaining how tumors elevate PKMYT1.

    Evidence ChIP, luciferase reporters, MeRIP-seq, RNA pulldown with MS, and rescue experiments across cancer models

    PMID:35114989 PMID:36988891 PMID:37729973 PMID:38253021

    Open questions at the time
    • Relative contribution of each regulator in normal tissue unknown
    • Direct kinase-pathway coupling for several axes (e.g., metabolic outputs) not established
  6. 2023 Medium

    Defined WEE1 as a pharmacological synthetic-lethal partner, showing combined inhibition drives replication catastrophe and inflammatory STAT1 signaling.

    Evidence Inhibitor combinations in ovarian cancer cells and organoids with CDK activity and DNA damage readouts

    PMID:37325550

    Open questions at the time
    • Mechanism linking replication stress to STAT1 not fully resolved
    • Single lab
  7. 2024 High

    Extended the dependency landscape to LMW-E, PLK1 regulation, and TP53/PRKDC context, refining biomarkers and revealing non-canonical effectors beyond CDK1 phosphorylation.

    Evidence Genome-wide CRISPR screens, PLK1 phosphorylation analysis, proteogenomics, transgenic and PDX models with RP-6306

    PMID:38570712 PMID:39186665

    Open questions at the time
    • Direct kinase-substrate relationship for PLK1 regulation not established
    • Mechanism of LMW-E-specific PKMYT1 stabilization unresolved
  8. 2025 Medium

    Revealed PKMYT1 phosphorylates NPM1-S260 to impair DSB repair, defining a kinase-substrate axis that connects PKMYT1 to homologous-recombination factor recruitment and chemoresistance.

    Evidence Kinome CRISPR screen, phospho-site mapping, SUMOylation and Co-IP assays for BRCA1/RAP80/RAD51 recruitment in osteosarcoma

    PMID:40393983

    Open questions at the time
    • In vitro reconstitution of NPM1 phosphorylation not shown
    • Generality beyond osteosarcoma untested
  9. 2025 Medium

    Established the bidirectional control of PKMYT1 protein stability by USP49 (stabilizing) and TRIM25 (degrading), with meisoindigo acting as a molecular glue at Cys301 to drive K48 ubiquitination.

    Evidence Co-IP, ubiquitination assays, ABPP covalent target ID, and proteasome rescue with xenograft validation

    PMID:40279509 PMID:41443044

    Open questions at the time
    • No in vitro deubiquitinase reconstitution for USP49 (Low-confidence)
    • Physiological balance of USP49 vs TRIM25 not defined
  10. 2025 Medium

    Connected PKMYT1 inhibition to immune activation and cell death, showing RP-6306 triggers cGAS-STING, interferon signaling, CD8+ T-cell infiltration, and PANoptosis, broadening therapeutic rationale.

    Evidence Syngeneic mouse models, scRNA-seq, cGAS-STING and cell-death marker assays, combination with anti-PD-L1 and gemcitabine

    PMID:40664640 PMID:41617394

    Open questions at the time
    • Whether immune activation requires segregation errors vs replication stress not dissected
    • Durability of T-cell responses untested
  11. 2026 High

    Defined a CDK1-restraint-independent anaphase function for PKMYT1 in chromosome segregation and spindle assembly checkpoint integrity, establishing a mitotic role distinct from WEE1.

    Evidence Live-cell imaging, chromosome segregation and micronuclei quantification, SAC assays with anti-microtubule drugs, cGAS-STING activation

    PMID:42243523

    Open questions at the time
    • Anaphase substrate(s) of PKMYT1 not identified
    • Mechanism of SAC maintenance unresolved
  12. 2026 High

    Characterized a cryptic allosteric site on PKMYT1, revealing a P-loop conformational mechanism distinct from ATP-competitive engagement and expanding inhibitor design space.

    Evidence X-ray crystallography, ATP-competition kinetics, cellular engagement assays, and computational modeling

    PMID:42227652

    Open questions at the time
    • Cellular potency advantage of allosteric vs orthosteric inhibition not established
    • Selectivity profile across the kinome not fully mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • The substrate repertoire and recruitment mechanism underlying PKMYT1's anaphase and DNA-repair roles remain undefined, as does which contexts depend on kinase activity versus scaffolding interactions.
  • No anaphase substrate identified
  • Several reported binding partners (GSK3β, AKT1, MCRS1, cyclin A2) rest on single Co-IPs without reciprocal or reconstitution validation
  • Membrane-targeting determinants not characterized in the corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 3 GO:0016740 transferase activity 2 GO:0140097 catalytic activity, acting on DNA 1
Localization
GO:0005829 cytosol 1
Pathway
R-HSA-1640170 Cell Cycle 4 R-HSA-73894 DNA Repair 2 R-HSA-8953897 Cellular responses to stimuli 2
Partners
AKT1CCNA2CDK1GSK3BMCRS1NPM1TRIM25USP49

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2017 PKMYT1 is a dual-specificity kinase that phosphorylates CDK1 at both Thr14 and Tyr15 (whereas WEE1 exclusively phosphorylates Tyr15), thereby acting as a negative regulator of CDK1/Cyclin B and restraining G2/M transition. Biochemical characterization and review of cell cycle regulation mechanisms; in vitro kinase assays with Thr14/Tyr15 phospho-specific readouts Molecules (Basel, Switzerland) High 29168755
2011 PKMYT1 (human Myt1 kinase) phosphorylates only protein substrates, not peptide substrates, indicating a requirement for protein-level substrate recognition for both its Thr and Tyr kinase activities. PKMYT1 is insensitive to staurosporine in a kinase binding assay. Fluorescence polarization immunoassay, immunoblotting, in vitro kinase assays with peptide and protein substrates, molecular dynamics simulations Bioorganic & medicinal chemistry letters Medium 22189141
2015 PKMYT1 acts redundantly with WEE1 to inhibit Cyclin B-CDK1 activity via CDK1-Y15 phosphorylation and to promote timely completion of mitosis in normal neural stem cells (NSCs). In glioblastoma stem-like cells (GSCs), this redundancy is lost, likely due to oncogenic signaling, causing GBM-specific lethality upon PKMYT1 loss. Genome-wide CRISPR-Cas9 knockout screens in GSCs vs NSCs, in vitro and in vivo validation, CDK1-Y15 phosphorylation measurement Cell reports High 26673326
2022 CCNE1 amplification creates a synthetic lethal dependency on PKMYT1 kinase activity. PKMYT1 inhibition (with RP-6306) causes unscheduled CDK1 activation selectively in CCNE1-overexpressing cells, promoting early mitosis during DNA synthesis. CCNE1 overexpression disrupts CDK1 homeostasis at least in part through early activation of the MMB-FOXM1 mitotic transcriptional program. Genome-scale CRISPR-Cas9 synthetic lethality screens in CCNE1-amplified cell models, selective PKMYT1 inhibitor RP-6306 (orally bioavailable), CDK1 phosphorylation assays, xenograft models, transcriptional program analysis Nature High 35444283
2022 RP-6306 is an orally bioavailable and selective PKMYT1 inhibitor identified through structure-based drug design. Crystal structure analysis guided optimization of inhibitor interactions with PKMYT1 active site residues, achieving selectivity over the closely related WEE1 kinase. Structure-based drug design, in vitro PKMYT1 kinase assays, ADME profiling, xenograft tumor models Journal of medicinal chemistry High 35880755
2017 PKMYT1 promotes hepatocellular carcinoma cell growth and motility by binding to and inactivating GSK3β, thereby activating β-catenin/TCF signaling. Co-immunoprecipitation, western blotting, cell viability and migration assays, gene knockdown/overexpression in HCC cell lines Experimental cell research Low 28648520
2019 PKMYT1 interacts with MCRS1 protein; immunoprecipitation confirmed the interaction, and immunofluorescence showed co-localization of MCRS1 and PKMYT1 in the cytoplasm of gastric cancer cells. MCRS1 overexpression suppresses PKMYT1 expression and inhibits GC cell proliferation, invasion, and migration. Co-immunoprecipitation, immunofluorescence co-localization, yeast two-hybrid (previous study), WEE1 inhibitor rescue experiments Cellular signalling Low 30953699
2020 PKMYT1 silencing inhibits G2/M checkpoint-mediated radiation resistance in lung adenocarcinoma: knockdown of PKMYT1 abrogates IR-induced G2/M phase arrest and increases sensitivity of cancer cells to radiation. siRNA knockdown of PKMYT1, colony survival assay, cell cycle analysis by flow cytometry after ionizing radiation Frontiers in genetics Medium 32411179
2021 PKMYT1 binds to cyclin A2 (CCNA2) as demonstrated by co-immunoprecipitation; knockdown of PKMYT1 reduces CCNA2 expression and inhibits proliferation, EMT, migration, and invasion in oral squamous cell carcinoma cells. Co-immunoprecipitation, shRNA knockdown, CCK-8, colony formation, wound healing, Transwell assays, western blot Oncology letters Low 35069872
2022 PKMYT1 demethylation of PKMYT1 mRNA m6A sites is regulated by ALKBH5 (m6A demethylase); ALKBH5 knockdown or demethylase activity mutation upregulates PKMYT1 expression. IGF2BP3 acts as the m6A reader that stabilizes PKMYT1 mRNA via its m6A modification site. MeRIP-seq, MeRIP-qRT-PCR, RNA pulldown, mass spectrometry, RNA immunoprecipitation (RIP), RNA-seq, in vivo lung metastasis model Molecular cancer Medium 35114989
2022 PKMYT1 directly binds AKT1 and abrogates AKT1 kinase activation in lung adenocarcinoma cells; this tumor-suppressive function depends on PKMYT1's tyrosine and threonine kinase activity. Co-immunoprecipitation (direct binding assay), RNA-seq, AKT pathway inhibitors, knockdown/overexpression with proliferation and invasion assays Cellular oncology (Dordrecht, Netherlands) Low 36350496
2023 Combined WEE1 and PKMYT1 inhibition synergistically promotes CDK activation, exacerbates DNA replication stress and replication catastrophe, and activates inflammatory STAT1 signaling in ovarian cancer cells, demonstrating that PKMYT1 and WEE1 are synthetic lethal partners. Small-molecule inhibitor combinations in ovarian cancer cells and organoid models, CDK activity assays, DNA damage markers, STAT1 pathway analysis NAR cancer Medium 37325550
2023 ELF3 transcription factor upregulates PKMYT1 expression by binding the PKMYT1 promoter region in gallbladder cancer cells, thereby promoting phosphorylation of CDK1 and inducing gemcitabine resistance via the ELF3/PKMYT1/CDK1 axis. Luciferase reporter assay, ChIP assay, western blot for CDK1 phosphorylation, shRNA knockdown, in vivo xenograft models Cellular oncology (Dordrecht, Netherlands) Medium 36988891
2023 TEAD4 transcriptionally activates PKMYT1 by binding its promoter; TEAD4-driven PKMYT1 upregulation facilitates glycolysis and proliferation in gastric cancer cells. Dual-luciferase assay, chromatin immunoprecipitation (ChIP), JASPAR database prediction, CCK-8, colony formation, extracellular acidification rate measurement Molecular and cellular probes Medium 37729973
2024 PKMYT1 inhibition in CCNE1-amplified cancers functions in addition to its canonical CDK1-phosphorylating role by regulating PLK1 expression and phosphorylation, promoting PDAC tumorigenesis. TP53 function and PRKDC activation modulate sensitivity to PKMYT1 inhibition. Genome-wide CRISPR screens, PLK1 expression/phosphorylation analysis, in vitro cell line models, xenograft models (CDX and PDX), pharmacological PKMYT1 inhibition EMBO molecular medicine Medium 38570712
2024 Low-molecular weight cyclin E (LMW-E) specifically upregulates PKMYT1 expression and protein stability compared to full-length cyclin E, increasing CDK1 phosphorylation. PKMYT1 inhibition in this context accelerates premature mitotic entry, inhibits replication fork restart, and enhances DNA damage and apoptosis in an LMW-E-dependent manner. Tumor sample proteogenomics, cell line LMW-E expression, PKMYT1 inhibitor RP-6306, CDK1 phosphorylation assays, replication fork assays, DNA damage markers, LMW-E transgenic murine mammary tumor models, PDX models Cancer research High 39186665
2024 X-ray co-crystal structure of PKMYT1 with inhibitor compounds confirmed that binding interactions with residues Asp251 and Tyr121 in the PKMYT1 active site are critical for potency and selectivity over WEE1. X-ray crystallography (co-crystal structure of PKMYT1 with inhibitors), structure-activity relationship analysis Journal of medicinal chemistry High 39163619
2023 Molecular dynamics simulations and binding free energy calculations identified that the non-conserved gatekeeper residue Thr187 in PKMYT1 (vs Asn376 in WEE1) is a critical determinant of binding selectivity for RP-6306 toward PKMYT1 over WEE1. A water-mediated hydrogen bond between RP-6306 and Gly191 at the PKMYT1 hinge domain is absent in the WEE1 complex. Molecular docking, multiple microsecond-length molecular dynamics simulations, end-point free energy calculations (MM-PBSA/GBSA), per-residue free energy decomposition Journal of biomolecular structure & dynamics Low 37345529
2025 PKMYT1 phosphorylates nucleophosmin 1 (NPM1) at the S260 site in osteosarcoma cells. This phosphorylation competitively impairs NPM1 SUMOylation, which in turn interferes with recruitment of BRCA1, RAP80, and RAD51 to double-strand break sites, thereby impairing DSB repair and promoting chemoresistance to cisplatin. Kinome-wide CRISPR screen, transcriptome sequencing, phosphorylation site mapping (NPM1-S260), SUMOylation assay, co-immunoprecipitation for BRCA1/RAP80/RAD51 recruitment, in vitro functional assays, patient-derived clinical specimens Signal transduction and targeted therapy Medium 40393983
2025 Meisoindigo (Mei) forms a selective and reversible covalent bond with the Cys301 residue of PKMYT1, acting as a molecular glue that enhances the interaction between PKMYT1 and the E3 ubiquitin ligase TRIM25 by approximately 30-fold. This triggers K48-linked polyubiquitination and proteasomal degradation of PKMYT1. Activity-based protein profiling (ABPP), covalent binding characterization, ubiquitination assays (K48-linkage), co-immunoprecipitation of PKMYT1-TRIM25 interaction, proteasome inhibitor rescue experiments, xenograft model Advanced science (Weinheim, Baden-Wurttemberg, Germany) Medium 40279509
2025 USP49 deubiquitinase interacts with PKMYT1 and limits its ubiquitination and subsequent proteasomal degradation, thereby stabilizing PKMYT1 protein levels in triple-negative breast cancer cells. Overexpression of PKMYT1 rescues malignant phenotypes in USP49-deficient TNBC cells. Co-immunoprecipitation of USP49-PKMYT1, ubiquitination assays, siRNA knockdown, rescue overexpression, cell viability and cell cycle assays Biochemical and biophysical research communications Low 41443044
2025 PKMYT1 inhibition (RP-6306) activates the cGAS-STING pathway and potentiates type I and II interferon signaling, upregulating chemokines CCL5 and CXCL10, thereby enhancing CD8+ T cell infiltration and synergizing with PD-L1 blockade in castration-resistant prostate cancer models. PCa cell lines and syngeneic mouse models, single-cell RNA sequencing, pharmacological PKMYT1 inhibition (RP-6306), flow cytometry for T cell infiltration, cGAS-STING pathway assays, combination with anti-PD-L1 Journal for immunotherapy of cancer Medium 41617394
2026 PKMYT1 kinase activity increases during anaphase and plays a novel mitotic role distinct from WEE1: chemical inhibition of PKMYT1 induces premature anaphase leading to chromosome segregation errors (chromatin bridges and micronuclei), which activate the cGAS-STING pathway. PKMYT1 also contributes to maintaining spindle assembly checkpoint integrity, as its inhibition promotes mitotic slippage in the presence of anti-microtubule drugs. PKMYT1 thus acts alongside Cyclin B1 degradation to control CDK1-Cyclin B1 activity during metaphase-to-anaphase transition. Chemical inhibition of PKMYT1 with live-cell imaging, chromosome segregation error analysis, micronuclei and chromatin bridge quantification, cGAS-STING pathway activation assays, spindle assembly checkpoint assays with anti-microtubule drugs EMBO reports High 42243523
2026 PKMYT1 directly activates Snail transcription in clear cell renal cell carcinoma by upregulating FoxM1, which represses E-cadherin and activates vimentin expression, thereby inducing EMT. Inhibition of the FoxM1/Snail/EMT pathway reversed PKMYT1-induced metastasis in mice. Exogenous PKMYT1 modulation, in vitro migration/invasion assays, EMT marker western blot, in vivo mouse metastasis model, FoxM1/Snail pathway analysis Cell biology international Low 41693360
2026 Allosteric inhibitor P29 binds a previously unknown cryptic allosteric site on PKMYT1, inducing conformational rearrangement of the P-loop and inhibiting PKMYT1 through a mixed ATP-competitive and non-competitive mechanism. A closely related analogue P32 engages PKMYT1 in the ATP binding pocket despite similar structure. X-ray crystallography, kinetic mechanistic assays (ATP competition), cell-based engagement assays, computational structural modeling (AlphaFold2/3, MD simulations) Journal of the American Chemical Society High 42227652
2025 Rb1 loss in breast cancer creates synthetic lethality with combined ATR and PKMYT1 coinhibition. Rb1 deficiency impairs double-strand DNA repair by attenuating homologous recombination and non-homologous end joining, leading to replication fork collapse. Coinhibition of ATR (S-G2 checkpoint) and PKMYT1 (G2-M checkpoint) leads to replication stress, premature mitotic entry, and DNA damage accumulation, with JNK/p38 stress response pathway activation driving apoptosis. In vitro coinhibition in Rb1-deficient vs proficient cell lines, genetic Rb1 knockdown/re-expression, PDX in vivo models, γH2AX/Ki67 biomarker analysis, HR and NHEJ repair assays, proteogenomic pathway analysis Science translational medicine High 41442499
2024 E2F7 transcription factor directly activates PKMYT1 transcription by binding to the PKMYT1 promoter in gastric cancer cells; the E2F7/PKMYT1 axis promotes proliferation and reduces adriamycin (ADM) sensitivity through MAPK pathway activation. Dual-luciferase reporter assay, chromatin immunoprecipitation (ChIP), western blot (ERK/p-ERK), CCK-8 assay, IC50 determination, rescue experiments Revista de investigacion clinica Medium 38253021
2024 PKMYT1 promotes SREBP2-mediated expression of cholesterol biosynthesis enzymes through activating the TNF/TRAF1/AKT pathway in triple-negative breast cancer cells. PKMYT1 knockdown, SREBP2 activity assays, cholesterol biosynthesis enzyme expression analysis, TNF/TRAF1/AKT pathway western blot, atorvastatin sensitivity assays PeerJ Low 39011373
2025 PKMYT1 inhibition with RP-6306 induces premature mitotic entry, causing DNA damage and mitotic catastrophe that triggers PANoptosis (concurrent apoptosis, pyroptosis, and necroptosis) in pancreatic cancer cells. PKMYT1 inhibitor RP-6306, in vitro cell death assays, PANoptosis marker analysis (apoptosis/pyroptosis/necroptosis), in vivo xenograft models, combination with gemcitabine Cell death & disease Medium 40664640

Source papers

Stage 0 corpus · 73 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2022 Demethylase ALKBH5 suppresses invasion of gastric cancer via PKMYT1 m6A modification. Molecular cancer 198 35114989
2022 CCNE1 amplification is synthetic lethal with PKMYT1 kinase inhibition. Nature 186 35444283
2017 Regulation of G2/M Transition by Inhibition of WEE1 and PKMYT1 Kinases. Molecules (Basel, Switzerland) 167 29168755
2015 Genome-wide CRISPR-Cas9 Screens Reveal Loss of Redundancy between PKMYT1 and WEE1 in Glioblastoma Stem-like Cells. Cell reports 149 26673326
2022 Discovery of an Orally Bioavailable and Selective PKMYT1 Inhibitor, RP-6306. Journal of medicinal chemistry 60 35880755
2017 PKMYT1 promoted the growth and motility of hepatocellular carcinoma cells by activating beta-catenin/TCF signaling. Experimental cell research 41 28648520
2020 PKMYT1 is associated with prostate cancer malignancy and may serve as a therapeutic target. Gene 37 32234541
2019 Systematic expression analysis of WEE family kinases reveals the importance of PKMYT1 in breast carcinogenesis. Cell proliferation 36 31837068
2020 PKMYT1 Promotes Gastric Cancer Cell Proliferation and Apoptosis Resistance. OncoTargets and therapy 32 32801781
2020 PKMYT1 as a Potential Target to Improve the Radiosensitivity of Lung Adenocarcinoma. Frontiers in genetics 30 32411179
2023 Synthetic lethal interaction between WEE1 and PKMYT1 is a target for multiple low-dose treatment of high-grade serous ovarian carcinoma. NAR cancer 24 37325550
2020 PKMYT1 aggravates the progression of ovarian cancer by targeting SIRT3. European review for medical and pharmacological sciences 24 32495859
2025 Targeting CCNE1 amplified ovarian and endometrial cancers by combined inhibition of PKMYT1 and ATR. Nature communications 21 40169546
2019 Effects of MCRS1 on proliferation, migration, invasion, and epithelial mesenchymal transition of gastric cancer cells by interacting with Pkmyt1 protein kinase. Cellular signalling 21 30953699
2024 Genome-wide CRISPR screens identify PKMYT1 as a therapeutic target in pancreatic ductal adenocarcinoma. EMBO molecular medicine 20 38570712
2018 Computer-aided design, synthesis and biological characterization of novel inhibitors for PKMYT1. European journal of medicinal chemistry 20 30388464
2024 Targeting Protein Kinase, Membrane-Associated Tyrosine/Threonine 1 (PKMYT1) for Precision Cancer Therapy: From Discovery to Clinical Trial. Journal of medicinal chemistry 18 39383322
2011 In vitro and in silico studies on substrate recognition and acceptance of human PKMYT1, a Cdk1 inhibitory kinase. Bioorganic & medicinal chemistry letters 18 22189141
2024 PKMYT1 Is a Marker of Treatment Response and a Therapeutic Target for CDK4/6 Inhibitor-Resistance in ER+ Breast Cancer. Molecular cancer therapeutics 16 38781103
2018 Identification of PKMYT1 inhibitors by screening the GSK published protein kinase inhibitor set I and II. Bioorganic & medicinal chemistry 14 29941193
2024 Low-Molecular Weight Cyclin E Confers a Vulnerability to PKMYT1 Inhibition in Triple-Negative Breast Cancer. Cancer research 13 39186665
2022 PKMYT1 inhibits lung adenocarcinoma progression by abrogating AKT1 activity. Cellular oncology (Dordrecht, Netherlands) 13 36350496
2021 PKMYT1 regulates the proliferation and epithelial-mesenchymal transition of oral squamous cell carcinoma cells by targeting CCNA2. Oncology letters 13 35069872
2024 Structure-Based Drug Design of 2-Amino-[1,1'-biphenyl]-3-carboxamide Derivatives as Selective PKMYT1 Inhibitors for the Treatment of CCNE1-Amplified Breast Cancer. Journal of medicinal chemistry 12 39163619
2025 Discovery of Naphthyridinone Derivatives as Selective and Potent PKMYT1 Inhibitors with Antitumor Efficacy. Journal of medicinal chemistry 10 40198752
2024 PKMYT1 Promotes Epithelial-Mesenchymal Transition Process in Triple-Negative Breast Cancer by Activating Notch Signaling. Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion 10 38442372
2024 Discovery of pyrrolopyrimidinone derivatives as potent PKMYT1 inhibitors for the treatment of cancer. European journal of medicinal chemistry 10 39515174
2022 KDM2B mediates the Wnt/β-catenin pathway through transcriptional activation of PKMYT1 via microRNA-let-7b-5p/EZH2 to affect the development of non-small cell lung cancer. Experimental cell research 10 35580699
2025 PKMYT1 kinase ameliorates cisplatin sensitivity in osteosarcoma. Signal transduction and targeted therapy 9 40393983
2023 Structural and energetic insights into the selective inhibition of PKMYT1 against WEE1. Journal of biomolecular structure & dynamics 9 37345529
2023 Transcription factor TEAD4 facilitates glycolysis and proliferation of gastric cancer cells by activating PKMYT1. Molecular and cellular probes 9 37729973
2021 The DNA damage repair-related gene PKMYT1 is a potential biomarker in various malignancies. Translational lung cancer research 9 35070764
2023 ELF3 promotes gemcitabine resistance through PKMYT1/CDK1 signaling pathway in gallbladder cancer. Cellular oncology (Dordrecht, Netherlands) 8 36988891
2022 Knockdown of PKMYT1 is associated with autophagy inhibition and apoptosis induction and suppresses tumor progression in hepatocellular carcinoma. Biochemical and biophysical research communications 8 36512849
2024 Structure-based virtual screening discovers novel PKMYT1 inhibitors. RSC medicinal chemistry 7 39309356
2024 PKMYT1 knockdown inhibits cholesterol biosynthesis and promotes the drug sensitivity of triple-negative breast cancer cells to atorvastatin. PeerJ 6 39011373
2024 Development of a novel treatment based on PKMYT1 inhibition for cisplatin-resistant bladder cancer with miR-424-5p-dependent cyclin E1 amplification. BMC cancer 6 39472827
2025 Meisoindigo Acts as a Molecular Glue to Target PKMYT1 for Degradation in Chronic Myeloid Leukemia Therapy. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 4 40279509
2023 PKMYT1: A Potential Target for CCNE1 Amplificated Colorectal Tumors. Cell biochemistry and biophysics 4 37572218
2022 c-Myb-mediated inhibition of miR-601 in facilitating malignance of osteosarcoma via augmentation of PKMYT1. Scientific reports 4 35461324
2025 Targeted delivery of the PKMYT1 inhibitor RP-6306 mediates PANoptosis in pancreatic cancer via mitotic catastrophe. Cell death & disease 3 40664640
2025 microRNA-497-5p-based screening identifies a novel synthetic lethal-type interaction via PKMYT1 and WEE1 in pleural mesothelioma. Molecular therapy. Nucleic acids 3 40673159
2024 Transcription factor E2F7 activates PKMYT1 to partially suppress adriamycin sensitivity in gastric cancer through the MAPK signaling pathway. Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion 3 38253021
2024 Targeting CCNE1 amplified ovarian and endometrial cancers by combined inhibition of PKMYT1 and ATR. Research square 3 38410486
2024 Discovery of novel and highly potent dual-targeting PKMYT1/HDAC2 inhibitors for hepatocellular carcinoma through structure-based virtual screening and biological evaluation. Frontiers in pharmacology 3 39619613
2025 Identification of TTLL8, POTEE, and PKMYT1 as immunogenic cancer-associated antigens and potential immunotherapy targets in ovarian cancer. Oncoimmunology 2 39891409
2025 Discovery of potent and selective PKMYT1 inhibitors for the treatment of CCNE1-amplified cancer. European journal of medicinal chemistry 2 40845413
2024 Novel Indazole Compounds as PKMYT1 Kinase Inhibitors for Treating Cancer. ACS medicinal chemistry letters 2 39563798
2025 Discovery of CMNPD31124 as a novel marine-derived PKMYT1 inhibitor for pancreatic ductal adenocarcinoma therapy: computational and biological insights. Frontiers in pharmacology 1 40290442
2025 Integrated multi-omics analysis identifies SELENOP and PKMYT1 as immune-metabolic hub genes in breast cancer. Biochemistry and biophysics reports 1 40821907
2026 Targeting PKMYT1 enhances antitumor immune responses to PD-L1 blockade in castration-resistant prostate cancer. Journal for immunotherapy of cancer 0 41617394
2026 Conformational restriction of hinge carboxamide leading to potent lactam-based PKMYT1 inhibitors. Bioorganic & medicinal chemistry 0 41643602
2026 PKMYT1/FOXM1/Snail Axis Promotes Metastasis in Clear Cell Renal Cell Carcinoma by Inducing Epithelial-mesenchymal Transition. Cell biology international 0 41693360
2026 An Internal Sulfur-Lone Pair Interaction Enabled the Discovery of Potent and Sub-Family Selective PKMYT1 Inhibitors. ChemMedChem 0 41885764
2026 ATR and PKMYT1 Inhibition Resensitizes a Subset of TNBC Patient-Derived Models to Carboplatin, Inducing Mitotic Catastrophe. Cancer research communications 0 41973002
2026 Novel Indazole Compounds as PKMYT1 Kinase Inhibitors for Treating Cancer. ACS medicinal chemistry letters 0 41982736
2026 ARID1A deficiency unleashes centromeric RNA transcription to drive chromosomal instability and boosts PKMYT1 inhibitor efficacy via RNA sensing. bioRxiv : the preprint server for biology 0 42039593
2026 Bevacizumab induces apoptosis in glioblastoma cells by upregulating miR-4695-5p to inhibit PKMYT1. RNA biology 0 42133791
2026 Recent advances in the discovery of PKMYT1-targeting drugs: a patent review (2021-2025). Expert opinion on therapeutic patents 0 42165607
2026 Allosteric Inhibition of PKMYT1 Induces a Unique, Inactive ATP Binding Site Conformation. Journal of the American Chemical Society 0 42227652
2026 PKMYT1 is a Targetable Vulnerability in del(17p) High-Risk Multiple Myeloma. Blood 0 42237635
2026 PKMYT1 has an important role in the timing and fidelity of chromosome segregation. EMBO reports 0 42243523
2026 Integrative Transcriptomic and Functional Analysis of PKMYT1 Reveals a Potential Therapeutic Target in Chronic Lymphocytic Leukemia. Hematological oncology 0 42249771
2025 Structure-based discovery and experimental validation of HIT101481851 as a potential PKMYT1 inhibitor for pancreatic cancer. Frontiers in pharmacology 0 40606600
2025 Unraveling resistance mechanisms to the novel nucleoside analog RX-3117 in lung cancer: insights into DNA repair, cell cycle dysregulation and targeting PKMYT1 for improved therapy. Journal of experimental & clinical cancer research : CR 0 40702552
2025 Exploring PKMYT1 as a potential marker for colorectal cancer progression through bioinformatics analyses and experimental validation. Scientific reports 0 41006713
2025 Design, Synthesis, and Computational Insights into PKMYT1 Inhibitors for the Treatment of Breast Cancer. Biomedicines 0 41007679
2025 E2F1-mediated PKMYT1 upregulation promotes prostate cancer progression by inhibiting the PPAR signaling pathway. Scientific reports 0 41390597
2025 Discovery of PKMYT1 Inhibitors with a Novel Scaffold for the Treatment of Triple-Negative Breast Cancer. Journal of medicinal chemistry 0 41427887
2025 Rb1 deficiency induces synthetic lethality with ATR and PKMYT1 coinhibition in breast cancer cell lines and patient-derived xenografts. Science translational medicine 0 41442499
2025 USP49 promotes the malignancy of triple-negative breast cancer cells by regulating PKMYT1 ubiquitination and stability. Biochemical and biophysical research communications 0 41443044
2025 PKMYT1 inhibition induces DNA damage and synergizes with immune checkpoint blockade in CCNE1 -amplified gastroesophageal adenocarcinoma. bioRxiv : the preprint server for biology 0 41446097
2025 Discovery of Tetracyclic Derivatives as Highly Potent, Selective, and Bioavailable PKMYT1 Inhibitors for Cancer Therapy. Journal of medicinal chemistry 0 41468420

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