We identified strong synergism for combined RRM2-CHK1 inhibition using the iron chelator triapine and prexasertib respectively. We confirm drug synergism in vivo in a NB zebrafish xenograft model, further underscoring the broad clinical potential of combinatorial RRM2-CHK1 inhibition. Altogether, this study paves the way for further preclinical testing of second generation RRM2 and CHK1 inhibitors such as TAS1553 and SRA737 in neuroblastoma and sarcomas.

9 days ago

Journal

RRM2 (Ribonucleotide Reductase Regulatory Subunit M2)

prexasertib (ACR-368) • SRA737 • Triapine (3-AP) • TAS1553

over2years

A Study of TAS1553 in Subjects With Relapsed or Refractory Acute Myeloid Leukemia (AML) and Other Myeloid Neoplasms (clinicaltrials.gov)

P1, N=20, Terminated, Astex Pharmaceuticals, Inc. | Trial completion date: Aug 2023 --> Feb 2023 | Active, not recruiting --> Terminated | Trial primary completion date: Aug 2023 --> Feb 2023; termination due to portfolio prioritization

over 2 years ago

Trial completion date • Trial termination • Trial primary completion date

TAS1553

over3years

TAS1553, a small molecule subunit interaction inhibitor of ribonucleotide reductase, exhibits antitumor activity by causing DNA replication stress. (PubMed, Commun Biol)

Oral administration of TAS1553 demonstrated robust antitumor efficacy against both hematological and solid cancer xenograft tumors and also provided a significant survival benefit in an acute myelogenous leukemia model. Our findings strongly support the evaluation of TAS1553 in clinical trials.

over 3 years ago

Journal

SLFN11 (Schlafen Family Member 11)

TAS1553

5years

A Study of TAS1553 in Subjects With Relapsed or Refractory Acute Myeloid Leukemia (AML) and Other Myeloid Neoplasms (clinicaltrials.gov)

Not yet recruiting --> Recruiting

5 years ago

Clinical • Enrollment open

CHEK1 (Checkpoint kinase 1)

TAS1553