MedKoo Cat#: 408019 | Name: TAS4464

Description:

WARNING: This product is for research use only, not for human or veterinary use.

TAS4464 is a highly potent and selective inhibitor of NEDD8 (IC50 of 0.955 nM). TAS4464 selectively inhibited NAE relative to the other E1s UAE and SAE. TAS4464 treatment inhibited cullin neddylation and subsequently induced the accumulation of CRL substrates such as CDT1, p27, and phosphorylated IκBα in human cancer cell lines. TAS4464 showed greater inhibitory effects than those of the known NAE inhibitor MLN4924 both in enzyme assay and in cells. Cytotoxicity profiling revealed that TAS4464 is highly potent with widespread antiproliferative activity not only for cancer cell lines but also patient derived tumor cells. TAS4464 showed 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. As a conclusion, TAS4464 is the most potent and highly selective NAE inhibitor reported to date, showing superior antitumor activity with prolonged target inhibition. It is, therefore, a promising agent for the treatment of a variety of tumors including both hematologic and solid tumors. These results support the clinical evaluation of TAS4464 in hematologic and solid tumors.

Chemical Structure

TAS4464
TAS4464
CAS#1848959-10-3

Theoretical Analysis

MedKoo Cat#: 408019

Name: TAS4464

CAS#: 1848959-10-3

Chemical Formula: C21H23FN6O6S

Exact Mass: 506.1384

Molecular Weight: 506.51

Elemental Analysis: C, 49.80; H, 4.58; F, 3.75; N, 16.59; O, 18.95; S, 6.33

Price and Availability

This product is currently not in stock but may be available through custom synthesis. To ensure cost efficiency, the minimum order quantity is 1 gram. The estimated lead time is 2 to 4 months, with pricing dependent on the complexity of the synthesis (typically high for intricate chemistries). Quotes for quantities below 1 gram will not be provided. To request a quote, please click the button below. Note: If this product becomes available in stock in the future, pricing will be listed accordingly.
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Related CAS #
No Data
Synonym
TAS4464; TAS-4464; TAS 4464.
IUPAC/Chemical Name
7H-Pyrrolo[2,3-d]pyrimidin-4-amine, 7-[5-[(aminosulfonyl)amino]-5-deoxy-beta-D-ribofuranosyl]-5-[2-(2-ethoxy-6-fluorophenyl)ethynyl]-
InChi Key
TZTRUHFXPVXWRD-QTQZEZTPSA-N
InChi Code
InChI=1S/C21H23FN6O6S/c1-2-33-14-5-3-4-13(22)12(14)7-6-11-9-28(20-16(11)19(23)25-10-26-20)21-18(30)17(29)15(34-21)8-27-35(24,31)32/h3-5,9-10,15,17-18,21,27,29-30H,2,8H2,1H3,(H2,23,25,26)(H2,24,31,32)/t15-,17-,18-,21-/m1/s1
SMILES Code
NC1=C2C(N([C@H]3[C@@H]([C@@H]([C@@H](CNS(=O)(N)=O)O3)O)O)C=C2C#CC4=C(F)C=CC=C4OCC)=NC=N1
Appearance
Solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
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 Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>3 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
NEDD8-activating enzyme (NAE) is an essential E1 enzyme of the NEDD8 conjugation (neddylation) pathway, which controls cancer cell growth and survival through activation of cullin-RING ubiquitin ligase complexes (CRLs). Cytotoxicity profiling revealed that TAS4464 is highly potent with widespread antiproliferative activity not only for cancer cell lines but also patient derived tumor cells. TAS4464 showed 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. As a conclusion, TAS4464 is the most potent and highly selective NAE inhibitor reported to date, showing superior antitumor activity with prolonged target inhibition. It is, therefore, a promising agent for the treatment of a variety of tumors including both hematologic and solid tumors. These results support the clinical evaluation of TAS4464 in hematologic and solid tumors.

Preparing Stock Solutions

The following data is based on the product molecular weight 506.51 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
1: Yoshimura C, Muraoka H, Ochiiwa H, Tsuji S, Hashimoto A, Kazuno H, Nakagawa F, Komiya Y, Suzuki S, Takenaka T, Kumazaki M, Fujita N, Mizutani T, Ohkubo S. 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. pii: molcanther.0644.2018. doi: 10.1158/1535-7163.MCT-18-0644. [Epub ahead of print] PubMed PMID: 31092565.