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    DRUG:

    fadraciclib (CYC065)

    i
    Other names: CYC065, CYC 065, CYC-065
    Company:
    Cyclacel
    Drug class:
    CDK2/9 inhibitor
    4ms
    Novel CDK2/CDK9 inhibitor fadraciclib targets cell survival and DNA damage pathways and synergizes with encorafenib in human colorectal cancer cells with BRAF(V600E). (PubMed, Oncogenesis)
    In conclusion, fadraciclib depletes MCL-1 to potentiate apoptosis and, combined with encorafenib, synergistically suppresses tumor cell growth in a BRAFV600E gene dose-dependent manner. These data suggest a novel therapeutic strategy in CRCs with BRAFV600E.
    Journal • PARP Biomarker
    |
    BRAF (B-raf proto-oncogene) • MCL1 (Myeloid cell leukemia 1) • CASP3 (Caspase 3)
    |
    BRAF V600E • BRAF V600 • BRAF wild-type
    |
    Braftovi (encorafenib) • fadraciclib (CYC065)
    4ms
    CDK inhibitors promote neuroblastoma cell differentiation and increase sensitivity to retinoic acid-a promising combination strategy for therapeutic intervention. (PubMed, Cell Death Discov)
    This study investigated three CDKis (abemaciclib, fadraciclib, and dinaciclib) alone or combined with retinoic acid (RA) to assess the effects on morphology, growth, gene expression, and the induction of immunogenic cell death in NB cell lines with (LAN-1 and CHLA-90) and without (CHLA-172) MYCN amplification. CDKi treatments promote NB differentiation via ER stress, with cytotoxicity enhanced by RA co-treatment. This may increase NB immunogenicity and support immunotherapy eligibility.
    Journal • IO biomarker
    |
    CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • CDK4 (Cyclin-dependent kinase 4) • CALR (Calreticulin) • CCNE2 (Cyclin E2) • MCM4 (Minichromosome Maintenance Complex Component 4) • MYBL2 (MYB Proto-Oncogene Like 2) • ROBO2 (Roundabout Guidance Receptor 2)
    |
    CDKN2A deletion
    |
    Verzenio (abemaciclib) • fadraciclib (CYC065) • dinaciclib (MK-7965)
    9ms
    Development of 9H-purine scaffold as novel CDK2 inhibitors: Design, synthesis, and biological evaluation. (PubMed, Bioorg Med Chem Lett)
    In this study, three series of compounds were designed and synthesized, using the CDK2 inhibitor fadraciclib (CYC065) as the lead compound, with 9H-purine as the core structure...This study evaluated the impact of substitutions at the 2, 6, and 9 positions of the purine ring on the activity of CDK2 small molecule inhibitors. The findings offer a theoretical foundation for future research, broadening the structural diversity and scope of CDK2 inhibitor studies.
    Journal
    |
    CCNE2 (Cyclin E2)
    |
    fadraciclib (CYC065)
    10ms
    Design, Synthesis and Biological Evaluation of Novel 9H Purine Derivatives as Potent CDK9 Inhibitors. (PubMed, Chem Biol Drug Des)
    Taking the CDK2/9 inhibitor CYC065 as the positive control and an in-house library compound (64) as the lead compound, four classes of 22 target compounds with 9H purine as the core structure were designed to establish structure-activity relationships (SAR)...After conducting selectivity testing against CDK2/9 kinase, compound B5 demonstrated approximately five-fold greater selectivity towards CDK9-cyclinT1 over CDK2-cyclinE2. This work also provides a reference basis for the subsequent research on CDK9 inhibitors.
    Journal
    |
    CCNE2 (Cyclin E2) • CLINT1 (Clathrin Interactor 1)
    |
    fadraciclib (CYC065)
    11ms
    ESMART: European Proof-of-Concept Therapeutic Stratification Trial of Molecular Anomalies in Relapsed or Refractory Tumors (clinicaltrials.gov)
    P1/2, N=455, Recruiting, Gustave Roussy, Cancer Campus, Grand Paris | Trial completion date: Aug 2027 --> Feb 2031 | Trial primary completion date: Aug 2027 --> Feb 2031
    Trial completion date • Trial primary completion date
    |
    Opdivo (nivolumab) • Lynparza (olaparib) • carboplatin • everolimus • temozolomide • Koselugo (selumetinib) • cytarabine • Bavencio (avelumab) • cyclophosphamide • Kisqali (ribociclib) • adavosertib (AZD1775) • Lytgobi (futibatinib) • irinotecan • Tabrecta (capmatinib) • Idhifa (enasidenib) • ceralasertib (AZD6738) • topotecan • fadraciclib (CYC065) • vistusertib (AZD2014) • peposertib (M3814) • lirilumab (BMS-986015)
    1year
    Absorption, Metabolism, and Excretion of CYC065 in Healthy Male Subjects (clinicaltrials.gov)
    P1, N=8, Completed, Cyclacel Pharmaceuticals, Inc. | Active, not recruiting --> Completed | Trial completion date: Feb 2024 --> May 2024 | Trial primary completion date: Mar 2023 --> Feb 2024
    Trial completion • Trial completion date • Trial primary completion date
    |
    fadraciclib (CYC065)
    almost2years
    A Study to Investigate Fadraciclib (CYC065), in Subjects With Leukemia or Myelodysplastic Syndrome (MDS) (clinicaltrials.gov)
    P1/2, N=210, Suspended, Cyclacel Pharmaceuticals, Inc. | Recruiting --> Suspended
    Trial suspension
    |
    BRAF (B-raf proto-oncogene) • CDK9 (Cyclin Dependent Kinase 9)
    |
    fadraciclib (CYC065)
    almost2years
    A Pharmacologic Study of CYC065, a Cyclin Dependent Kinase Inhibitor, in Patients With Advanced Cancers (clinicaltrials.gov)
    P1, N=60, Completed, Cyclacel Pharmaceuticals, Inc. | Active, not recruiting --> Completed
    Trial completion • Metastases
    |
    fadraciclib (CYC065)
    almost2years
    A Study to Investigate Fadraciclib (CYC065), in Subjects With Advanced Solid Tumors and Lymphoma (clinicaltrials.gov)
    P1/2, N=330, Recruiting, Cyclacel Pharmaceuticals, Inc. | Trial completion date: Dec 2023 --> Jun 2025 | Trial primary completion date: Oct 2023 --> Apr 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    CDK9 (Cyclin Dependent Kinase 9)
    |
    fadraciclib (CYC065)
    almost2years
    Absorption, Metabolism, and Excretion of CYC065 in Healthy Male Subjects (clinicaltrials.gov)
    P1, N=8, Active, not recruiting, Cyclacel Pharmaceuticals, Inc. | Trial completion date: Oct 2023 --> Jan 2024 | Trial primary completion date: Aug 2023 --> Mar 2023
    Trial completion date • Trial primary completion date
    |
    fadraciclib (CYC065)
    almost2years
    CYC065 CDK Inhibitor and Venetoclax Study in Relapsed/Refractory AML or MDS (clinicaltrials.gov)
    P1, N=14, Completed, Cyclacel Pharmaceuticals, Inc. | Active, not recruiting --> Completed | N=25 --> 14 | Trial completion date: Sep 2023 --> Apr 2023
    Trial completion • Enrollment change • Trial completion date
    |
    Venclexta (venetoclax) • fadraciclib (CYC065)
    almost2years
    CYC065 CDK Inhibitor and Venetoclax Study in Relapsed/Refractory CLL (clinicaltrials.gov)
    P1, N=5, Completed, Cyclacel Pharmaceuticals, Inc. | Active, not recruiting --> Completed | N=25 --> 5
    Trial completion • Enrollment change
    |
    Venclexta (venetoclax) • fadraciclib (CYC065)