TAS4464 free base · Synonyms: TAS-4464 · TAS 4464

TAS4464 is a highly potent and selective inhibitor of NEDD8 activating enzyme.

For research use only. Not for human or veterinary use.

Target Apoptosis Carbonic Anhydrase NEDD8-activating Enzyme

Research area Cancer

Purity >98% Stock Inquire

Data Sheet SDS COA

TAS4464 structure

CAS No.: 1848959-10-3

Download structure (.mol)

Pack sizes & pricing

Size	Price	SKU	Stock
100 mg	USD 485.00	BP-01937-100mg	In stock	Get quote
250 mg	USD 785.00	BP-01937-250mg	In stock	Get quote
500 mg	USD 1,185.00	BP-01937-500mg	In stock	Get quote
1 g	Inquire	BP-01937-1g	Inquire	Inquire
5 g	Inquire	BP-01937-5g	Inquire	Inquire

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Description

TAS4464 is a highly potent and selective inhibitor of NEDD8 activating enzyme (NAE), with an IC50 of 0.955 nM.

Biological activity

TAS4464 is a highly potent and selective recombinant NAE inhibitor, with over 470-fold and 1340-fold selectivity against recombinant UAE and SAE, respectively, and weak off-target inhibitory activity against CA2. TAS4464 (1-10 μM; 24-48 h) induces apoptosis in leukemia, lymphoma, multiple myeloma and solid tumor cell lines, with the apoptosis rate increasing as the drug concentration rises. TAS4464 (1 nM-1 μM, 4 h; 100 nM, 1-24 h) significantly increases the protein expression levels of CRL ubiquitin ligase substrates CDT1, p27, and phosphorylated IκBα in tumor cells, while reduces the level of cullin neddylation modification. TAS4464 (0.1-10 μM; 24-48 h) significantly inhibits the migratory capacity of solid tumor cell lines such as colorectal cancer and sarcoma, with a concentration-dependent inhibitory effect. In Vivo TAS4464 (25-100 mg/kg; i.v.; twice weekly; 3 weeks) hydrochloride achieves complete tumor regression and induces apoptosis in models of T-cell acute lymphoblastic leukemia (25 mg/kg), mantle cell lymphoma (100 mg/kg), clear cell sarcoma (100 mg/kg), and small cell lung cancer (75 mg/kg), with a broad selective window. TAS4464 (100 mg/kg; i.v.; administered on days 1, 4, 8 and 11, with one cycle every 21 days; 8 cycles total) hydrochloride significantly prolongs survival and reduces tumor burden in a systemic diffuse large B-cell lymphoma model of SCID mice xenografted with TMD8-Luc.

Identifiers

SMILES: CCOC1=C(C(=CC=C1)F)C#CC2=CN(C3=NC=NC(=C23)N)[C@H]4[C@@H]([C@@H]([C@H](O4)CNS(=O)(=O)N)O)O
InChIKey: TZTRUHFXPVXWRD-QTQZEZTPSA-N

Specifications

MW (average): 506.5070
Formula: C₂₁H₂₃FN₆O₆S
CAS No.: 1848959-10-3
Physical state: Solid
Color: Off-white to light yellow
Shipping: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage: Powder -20℃ 2 years; In solvent -20℃ 1 month;

Solubility

Soluble in DMSO

Documents

References

[1]. Yoshimura C, et al. TAS4464, a highly potent and selective inhibitor of NEDD8 activating enzyme, suppresses neddylation and shows antitumor activity in diverse cancer models. Mol Cancer Ther. 2019 May 15.

Same target

Search Apoptosis

Same research area

Search Cancer