TAS4464

Catalog No.S8849

For research use only.

TAS4464 is a potent and highly selective NEDD8 activating enzyme (NAE) inhibitor with IC50 of 0.955 nM. TAS4464 exhibits superior antitumor activity with prolonged target inhibition.

TAS4464 Chemical Structure

CAS No. 1848959-10-3

Purity & Quality Control

Choose Selective E1 Activating Inhibitors

Biological Activity

Description TAS4464 is a potent and highly selective NEDD8 activating enzyme (NAE) inhibitor with IC50 of 0.955 nM. TAS4464 exhibits superior antitumor activity with prolonged target inhibition.
Targets
NAE [1]
(Cell-free assay)
0.955 nM
In vitro

TAS4464 selectively inhibits NAE relative to the other E1s UAE and SAE. TAS4464 treatment inhibits cullin neddylation and subsequently induces the accumulation of CRL substrates such as CDT1, p27, and phosphorylated IkBa in human cancer cell lines. Cytotoxicity profiling reveals that TAS4464 is highly potent with widespread antiproliferative activity not only for cancer cell lines, but also patient-derived tumor cells.[1]

In vivo

TAS4464 shows prolonged target inhibition in human tumor xenograft mouse models; weekly or twice a week TAS4464 administration led to prominent antitumor activity in multiple human tumor xenograft mouse models including both hematologic and solid tumors without marked weight loss.[1]

Protocol (from reference)

Cell Research:

[1]

  • Cell lines: PBMC, AML, DLBCL, SCLC cells. Patient-derived ovary and endometrial cells. Hepatocytes.
  • Concentrations: 1 nM, 10 nM, 100 nM, 1000 nM
  • Incubation Time: 24 h, 72 h, 6 days
  • Method:

    PBMC, AML, DLBCL, and SCLC cells are treated with TAS4464 for 72 hours, after which viability is measured. Patient-derived ovary and endometrial cells are maintained in low-attachment plates and treated with TAS4464 or chemotherapeutic agents for 6 days. Cell viability is then measured by using the CellTiter-Glo 3D Cell Viability Assay. Hepatocytes are cultured in Cell-able plate for 10 days and then treated with TAS4464 for 24 hours, after which viability is measured by using CellTiter-Glo 3D Cell Viability Assay.

Animal Research:

[1]

  • Animal Models: 6-week-old female NOD-SCID mice
  • Dosages: 100 mg/kg, 75 mg/kg
  • Administration: IV

Solubility (25°C)

In vitro

Chemical Information

Molecular Weight 506.51
Formula

C21H23FN6O6S

CAS No. 1848959-10-3
Storage 3 years -20°C powder
2 years -80°C in solvent

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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT02978235 Terminated Drug: TAS4464 Multiple Myeloma|NonHodgkin Lymphoma Taiho Oncology Inc. March 1 2017 Phase 1

(data from https://clinicaltrials.gov, updated on 2022-08-01)

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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