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    DRUG CLASS:

    PKMYT1 inhibitor

    Related drugs:
    6d
    PKMYT1 is a Targetable Vulnerability in del(17p) High-Risk Multiple Myeloma. (PubMed, Blood)
    RP-6306 also reduced tumor burden and extended survival in vivo in both xenograft and TP53-deficient syngeneic models. Collectively, our findings nominate PKMYT1 as an actionable target and support PKMYT1 inhibition as a biomarker-driven therapeutic strategy for patients with del(17p)/TP53-deficient MM.
    Journal
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    TP53 (Tumor protein P53) • PKMYT1 (Protein Kinase Membrane Associated Tyrosine/Threonine 1)
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    lunresertib (Debio2513)
    7d
    Debio 0123-106: A phase 1 trial to study how safe and tolerable Lunresertib is, alone or in Combination with RP-3500 or Debio 0123, whennadministered in patients with certain types of cancer (2023-510063-35-00)
    P1, N=63, Recruiting, Debiopharm International S.A. | N=38 --> 63
    Enrollment change
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    TP53 (Tumor protein P53) • POLE (DNA Polymerase Epsilon) • CCNE1 (Cyclin E1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • MUC16 (Mucin 16, Cell Surface Associated)
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    TP53 mutation
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    lunresertib (Debio2513) • camonsertib (RP-3500) • zedoresertib (Debio 0123)
    20d
    Recent advances in the discovery of PKMYT1-targeting drugs: a patent review (2021-2025). (PubMed, Expert Opin Ther Pat)
    The rapid advancement of PKMYT1 inhibitors and degraders underscores their potential as a synthetic‑lethal therapeutic strategy for cancers with CCNE1 amplification or FBXW7 alterations. Clinical proof‑of‑concept for this approach has been established by RP‑6306 trial outcomes, while insights from this comprehensive review are expected to inform strategies addressing the current limitations in this field.
    Review • Journal
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    CCNE1 (Cyclin E1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • CDK1 (Cyclin-dependent kinase 1) • PKMYT1 (Protein Kinase Membrane Associated Tyrosine/Threonine 1)
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    lunresertib (Debio2513)
    4ms
    RP-6306 in Patients With Advanced Cancer (clinicaltrials.gov)
    P2, N=28, Completed, Canadian Cancer Trials Group | Active, not recruiting --> Completed
    Trial completion
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • CCNE1 (Cyclin E1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • UGT1A1 (UDP glucuronosyltransferase family 1 member A1) • PPP2R1A (Protein Phosphatase 2 Scaffold Subunit Aalpha)
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    TP53 mutation • KRAS mutation • HER-2 amplification • RAS mutation
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    Herceptin (trastuzumab) • gemcitabine • 5-fluorouracil • irinotecan • leucovorin calcium • lunresertib (Debio2513) • camonsertib (RP-3500)
    5ms
    MYTHIC: Study of Lunresertib Alone or in Combination With RP-3500 or Debio 0123 in Patients With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=464, Recruiting, Debiopharm International SA | Trial completion date: Dec 2026 --> Jun 2028 | Trial primary completion date: Jun 2026 --> Dec 2027
    Trial completion date • Trial primary completion date
    |
    CCNE1 (Cyclin E1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • MUC16 (Mucin 16, Cell Surface Associated) • PPP2R1A (Protein Phosphatase 2 Scaffold Subunit Aalpha)
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    lunresertib (Debio2513) • camonsertib (RP-3500) • zedoresertib (Debio 0123)
    6ms
    PKMYT1 inhibition induces DNA damage and synergizes with immune checkpoint blockade in CCNE1 -amplified gastroesophageal adenocarcinoma. (PubMed, bioRxiv)
    We evaluated lunresertib (RP-6306), a selective first-in-class PKMYT1 inhibitor, in CCNE1 -amplified and wild-type GEA cell lines to define its effects on cell viability, DNA damage, and gene expression changes...In a syngeneic murine model of CCNE1 -amplified gastric cancer, we further identified that PKMYT1 inhibition induced T cell infiltration and tumor microenvironment remodeling, and synergized with anti-PD-1 therapy to drive tumor regression. Together, these results support further development of PKMYT1 inhibition in combination with PD-1 blockade for CCNE1 -amplified GEA.
    Journal • Checkpoint inhibition • PD(L)-1 Biomarker • IO biomarker
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    TP53 (Tumor protein P53) • CCNE1 (Cyclin E1) • PKMYT1 (Protein Kinase Membrane Associated Tyrosine/Threonine 1)
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    lunresertib (Debio2513)
    6ms
    GyneRep: Phase 1 Study of RP-6306 With Carboplatin and Paclitaxel in TP53 Ovarian and Uterine Cancer (clinicaltrials.gov)
    P1, N=6, Active, not recruiting, University Health Network, Toronto | N=24 --> 6 | Trial completion date: Dec 2026 --> Jan 2026 | Trial primary completion date: Dec 2026 --> Oct 2025
    Enrollment change • Trial completion date • Trial primary completion date
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    TP53 (Tumor protein P53)
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    TP53 mutation
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    carboplatin • paclitaxel • lunresertib (Debio2513)
    9ms
    Design, Synthesis, and Computational Insights into PKMYT1 Inhibitors for the Treatment of Breast Cancer. (PubMed, Biomedicines)
    Molecular dynamics simulations, Hirshfeld surface analysis, dynamic cross-correlation matrix (DCCM), and MM/GBSA calculations elucidated the molecular mechanism underlying MY-14's interaction with PKMYT1. MY-14 emerged as a promising compound for the development of a novel PKMYT1 inhibitor.
    Journal
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    CCNE1 (Cyclin E1) • PKMYT1 (Protein Kinase Membrane Associated Tyrosine/Threonine 1)
    10ms
    Discovery of potent and selective PKMYT1 inhibitors for the treatment of CCNE1-amplified cancer. (PubMed, Eur J Med Chem)
    Further investigations revealed that compound A30 exerted a highly synergistic effect with gemcitabine in CCNE1-amplified cancer models...Pharmacokinetic profiling indicated that compound A30 exhibits liver microsomal stability, favorable plasma stability, minimal CYPs inhibition, and acceptable overall pharmacokinetic properties. Together, these findings establish that compound A30 represents a promising lead for the further development of selective PKMYT1 inhibitors.
    Journal
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    CCNE1 (Cyclin E1) • PKMYT1 (Protein Kinase Membrane Associated Tyrosine/Threonine 1)
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    gemcitabine
    11ms
    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. (PubMed, J Exp Clin Cancer Res)
    By integrating CRISPR-Cas9 with functional assays and transcriptomics, our study established a framework for decoding resistance mechanisms and highlights potential therapeutic strategies to enhance RX-3117 efficacy in NSCLC. We demonstrated for the first time that aberrant DNA repair and cell cycle dysregulation led resistance, identifying PKMYT1 as a promising target.
    Journal
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    PKMYT1 (Protein Kinase Membrane Associated Tyrosine/Threonine 1)
    |
    gemcitabine • lunresertib (Debio2513) • roducitabine (PCS3117)
    11ms
    RP-6306 in Patients With Advanced Cancer (clinicaltrials.gov)
    P2, N=28, Active, not recruiting, Canadian Cancer Trials Group | Recruiting --> Active, not recruiting | N=78 --> 28
    Enrollment closed • Enrollment change
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    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • CCNE1 (Cyclin E1) • UGT1A1 (UDP glucuronosyltransferase family 1 member A1)
    |
    TP53 mutation • KRAS mutation • HER-2 amplification • RAS mutation
    |
    Herceptin (trastuzumab) • gemcitabine • 5-fluorouracil • irinotecan • leucovorin calcium • lunresertib (Debio2513) • camonsertib (RP-3500)
    12ms
    A Dose-escalation, Dose-finding, and Expansion Study of XL495 in Participants With Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
    P1, N=9, Terminated, Exelixis | N=124 --> 9 | Trial completion date: Nov 2027 --> May 2025 | Recruiting --> Terminated | Trial primary completion date: Nov 2027 --> May 2025; Company Decision
    Enrollment change • Trial completion date • Trial termination • Trial primary completion date