TAS4464

Catalog No.S8849 Batch:S884901

Technical Data

Formula

C₂₁H₂₃FN₆O₆S

Molecular Weight

506.51

CAS No.

1848959-10-3

Solubility (25°C)*

In vitro

DMSO

100 mg/mL (197.42 mM)

Water

Insoluble

Ethanol

Insoluble

In vivo (Add solvents to the product individually and in order)

Clear solution	5% DMSO 1 95% Corn oil	0.5mg/ml	Taking the 1 mL working solution as an example, add 50 μL of 10 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O	5.0mg/ml	Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

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 Assay:^{^[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 Study:^{^[1]}	Animal Models 6-week-old female NOD-SCID mice Dosages 100 mg/kg, 75 mg/kg Administration IV

Cell Assay:^{^[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 Study:^{^[1]}

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

References

[1] Chihoko Yoshimura, et al. Mol Cancer Ther. 2019 Jul;18(7):1205-1216.

Selleck's TAS4464 has been cited by 1 publication

The CUL5 E3 ligase complex negatively regulates central signaling pathways in CD8+ T cells [ Nat Commun, 2024, 15(1):603]	PubMed: 38242867

The CUL5 E3 ligase complex negatively regulates central signaling pathways in CD8+ T cells [ Nat Commun, 2024, 15(1):603]

PubMed: 38242867

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.