Home Ubiquitin E1 Activating inhibitor TAS4464 For research use only.

TAS4464

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

TAS4464 Chemical Structure

CAS No. 1848959-10-3

Purity & Quality Control

TAS4464 Related Products

Signaling Pathway

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E1 Activating Signaling Pathway

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
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]
Cell Research 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.
In Vivo
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]
Animal Research Animal Models 6-week-old female NOD-SCID mice
Dosages 100 mg/kg, 75 mg/kg
Administration IV
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02978235 Terminated
Multiple Myeloma|NonHodgkin Lymphoma
Taiho Oncology Inc.
 March 1 2017 Phase 1

Chemical Information & Solubility

Molecular Weight 506.51 Formula

C21H23FN6O6S
CAS No. 1848959-10-3 SDF --
Smiles CCOC1=CC=CC(=C1C#CC2=C[N](C3OC(CN[S](N)(=O)=O)C(O)C3O)C4=C2C(=NC=N4)N)F
Storage (From the date of receipt) 3 years -20°C powder

In vitro
Batch:

DMSO : 100 mg/mL ( (197.42 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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In vivo
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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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