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    DRUG CLASS:

    DNA methylation inhibitor

    Related drugs:
    4d
    Lack of Cancer Specificity of Methionine Adenosyltransferase 2A (MAT2A) Inhibitor AG-270 in Combination With Recombinant Methioninase In Vitro. (PubMed, Anticancer Res)
    AG-270 showed lack of cancer specificity in combination with rMETase when tested on both cancer and normal cells. The present results contrast with numerous chemotherapy agents, which in combination with rMETase are synergistic on cancer cells but not on normal cells. The present findings suggest that MAT2A inhibition affects crucial metabolic pathways in normal as well as cancer cell types and thus AG-270 may not be suitable as a cancer-specific therapeutic strategy.
    Preclinical • Journal
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    MAT2A (Methionine Adenosyltransferase 2A)
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    ONCase (recombinant methionine α, γ-lyase) • S095033
    1m
    ASCENT1: Research Study Investigating How Well NDec Works in People With Sickle Cell Disease (clinicaltrials.gov)
    P2, N=96, Completed, Novo Nordisk A/S | Trial primary completion date: Dec 2024 --> Jul 2025
    Trial primary completion date
    |
    hydroxyurea • decitabine/ tetrahydrouridine (EPI01)
    1m
    Human fibrosarcoma cells selected for ultra-high doxorubicin resistance, acquire trabectedin cross-resistance, remain sensitive to recombinant methioninase, and have increased c-MYC expression. (PubMed, Front Oncol)
    The findings indicate that rMETase can overcome ultra-high doxorubicin resistance in fibrosarcoma cells, likely through targeting methionine addiction, a universal metabolic vulnerability of cancer. These results support the potential clinical application of methionine restriction therapy to treat doxorubicin-resistant STS.
    Journal
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    MYC (V-myc avian myelocytomatosis viral oncogene homolog)
    |
    doxorubicin hydrochloride • Yondelis (trabectedin) • ONCase (recombinant methionine α, γ-lyase)
    3ms
    Azanucleoside treatment leads to B-cell precursor acute lymphoblastic leukemia. (PubMed, Blood Neoplasia)
    5-Aza-4'-thio-2'-deoxycytidine (ATC) is an azanucleoside cytidine analog under investigation in preclinical studies for solid tumors as a promising DNA methyltransferase 1 (DNMT1) inhibitor...Bisulfite sequencing and treatment with a noncovalent DNMT1 inhibitor indicated that methylated cytosines were preferred targets for mutagenesis. This study reveals that ATC exposure leads to both DNMT1-dependent and -independent mutagenesis and provides a direct link between ATC exposure, a complex mutational signature, and malignant transformation.
    Journal
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    RAG1 (Recombination Activating 1)
    |
    4'-Thio-2'-Deoxycytidine (TdCyd)
    4ms
    ASCENT1: Research Study Investigating How Well NDec Works in People With Sickle Cell Disease (clinicaltrials.gov)
    P2, N=96, Completed, Novo Nordisk A/S | Active, not recruiting --> Completed | Trial primary completion date: Aug 2025 --> Dec 2024
    Trial completion • Trial primary completion date
    |
    hydroxyurea • decitabine/ tetrahydrouridine (EPI01)
    8ms
    A Study of Oral Tetrahydrouridine-Decitabine in Relapsed or Refractory Myelodysplastic Syndromes (MDS) (clinicaltrials.gov)
    P1, N=20, Recruiting, EpiDestiny, Inc. | Not yet recruiting --> Recruiting
    Enrollment open
    |
    decitabine/ tetrahydrouridine (EPI01)
    8ms
    A Study of Oral Tetrahydrouridine-Decitabine in Relapsed or Refractory Myelodysplastic Syndromes (MDS) (clinicaltrials.gov)
    P1, N=20, Not yet recruiting, EpiDestiny, Inc.
    New P1 trial
    |
    decitabine/ tetrahydrouridine (EPI01)
    8ms
    A Study of Nicotinamide With Oral Tetrahydrouridine and Decitabine to Treat High Risk Sickle Cell Disease (clinicaltrials.gov)
    P1, N=20, Recruiting, EpiDestiny, Inc. | Trial completion date: Apr 2024 --> Apr 2027 | Trial primary completion date: Mar 2024 --> Oct 2026
    Trial completion date • Trial primary completion date
    |
    decitabine/ tetrahydrouridine (EPI01)
    9ms
    To Study the Oral Bioavailability of a New Combination Formation of Decitabine and Tetrahydrouridine in Healthy Males (clinicaltrials.gov)
    P1, N=10, Completed, EpiDestiny, Inc. | Recruiting --> Completed
    Trial completion
    |
    decitabine/ tetrahydrouridine (EPI01)
    9ms
    ASCENT1: Research Study Investigating How Well NDec Works in People With Sickle Cell Disease (clinicaltrials.gov)
    P2, N=84, Active, not recruiting, Novo Nordisk A/S | Trial primary completion date: Dec 2024 --> Aug 2025 | Recruiting --> Active, not recruiting
    Enrollment closed • Trial primary completion date
    |
    hydroxyurea • decitabine/ tetrahydrouridine (EPI01)
    10ms
    Efficacy of Methionine Restriction and the PARP-inhibitor Olaparib and Their Combination on BRCA1 Mutant and Wild-type Triple-negative Breast Cancer Cell Lines. (PubMed, Anticancer Res)
    Methionine restriction and olaparib showed synergistic efficacy on the BRCA1-mutant TNBC cell line HCC1937. The BRCA1-mutant cell line MDA-MB-436 was most sensitive to rMETase. The BRCA1/2 wild-type TNBC cell line MDA-MB-231 was sensitive to a methionine-free medium but resistant to olaparib. Therefore, methionine restriction has clinical potential for BRCA1/2 wild-type and BRCA1-mutant olaparib-resistant and -sensitive TNBC.
    Preclinical • Journal • BRCA Biomarker • PARP Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)
    |
    BRCA wild-type
    |
    Lynparza (olaparib) • ONCase (recombinant methionine α, γ-lyase)
    1year
    A Study to Test How Either a Capsule or a Tablet With NDec (Decitabine and Tetrahydrouridine) Works in the Body of Healthy People (clinicaltrials.gov)
    P1, N=44, Completed, Novo Nordisk A/S | Recruiting --> Completed
    Trial completion
    |
    decitabine/ tetrahydrouridine (EPI01)