MLN4924 [NAE Inhibitor]

Specifications / Handling

More Information
Product Details
Synonyms	Pevonedistat; Nedd8 E1 Activating Enzyme Inhibitor; TAK924
Product Type	Chemical
Properties
Formula	C₂₁H₂₅N₅O₄S . H₂O
MW	443.5 . 18.0
CAS	905579-51-3
Purity Chemicals	≥99%
Appearance	White solid.
Solubility	Soluble in DMSO (30mg/ml), ethanol (10mg/ml) or DMF (20mg/ml). Insoluble in water.
Identity	Determined by ¹H-NMR.
InChi Key	MPUQHZXIXSTTDU-QXGSTGNESA-N
Smiles	[H][C@@]1(C[C@H](O)[C@H](COS(N)(=O)=O)C1)N1C=CC2=C(N[C@H]3CCC4=CC=CC=C34)N=CN=C12
Shipping and Handling
Shipping	AMBIENT
Short Term Storage	+4°C
Long Term Storage	-20°C
Handling Advice	Protect from light and moisture.
Use/Stability	Stable for at least 2 years after receipt when stored at -20°C.
Documents
MSDS	Download PDF
Product Specification Sheet
Datasheet	Download PDF

Product-specific References

Description

Adenosine 5'-monophosphate (AMP) analog.
Potent, selective and cell permeable inhibitor of Nedd8 E1 Activating Enzyme (NAE) (IC₅₀=4.7nM). NEDD8 is an ubiquitin-like protein whose activity is required to activate cullin-RING ubiquitin E3 ligases (CRLs) responsible for the ubiquitination and proteasome-dependent turnover of certain substrates relevant to cancer cell survival.
Anticancer agent with in vitro and in vivo activity. By inhibiting the Neddylation pathway this molecule disrupts cullin-RING ligase activity, leading to inhibition of proliferation or apoptotic death of various human tumor cells through the deregulation of S-phase DNA synthesis.
Inhibits related enzymes ubiquitin-activating enzyme (UAE) and SUMO-activating enzyme (SAE) with IC₅₀ values of 1.5 and 8.2μM, respectively.
Angiogenesis inhibitor and autophagy inducer.
Antiviral agent. Exhibited pronounced antiviral activity against mouse and human cytomegalovirus, herpes simplex virus (HSV)-1 (including multi-drug resistant clinical isolates), HSV-2, adeno and influenza viruses.

Product References

Targeting NEDD8-activated cullin-RING ligases for the treatment of cancer: T.A. Soucy, et al.; Clin. Cancer Res. 15, 3912 (2009)
An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer: T.A. Soucy, et al.; Nature 458, 732 (2009)
Substrate-assisted inhibition of ubiquitin-like protein-activating enzymes: the NEDD8 E1 inhibitor MLN4924 forms a NEDD8-AMP mimetic in situ: J.E. Brownell, et al.; Mol. Cell. 37, 102 (2010)
MLN4924, a NEDD8-activating enzyme inhibitor, is active in diffuse large B-cell lymphoma models: rationale for treatment of NF-{kappa}B-dependent lymphoma: M.A. Milhollen, et al.; Blood 116, 1515 (2010)
NEDD8-targeting drug MLN4924 elicits DNA rereplication by stabilizing Cdt1 in S phase, triggering checkpoint activation, apoptosis, and senescence in cancer cells: J.J. Lin, et al.; Cancer Res. 70, 10310 (2010)
The Nedd8-activating enzyme inhibitor MLN4924 induces autophagy and apoptosis to suppress liver cancer cell growth: Z. Luo, et al.; Cancer Res. 72, 3360 (2012)
MLN4924: a novel first-in-class inhibitor of NEDD8-activating enzyme for cancer therapy: S.T. Nawrocki, et al.; Expert. Opin. Investig. Drugs 21, 1563 (2012) (Review)
Inactivation of the Cullin (CUL)-RING E3 ligase by the NEDD8-activating enzyme inhibitor MLN4924 triggers protective autophagy in cancer cells: Z. Luo, et al.; Autophagy 8, 1677 (2012)
MLN4924, an NAE inhibitor, suppresses AKT and mTOR signaling via upregulation of REDD1 in human myeloma cells: Y. Gu, et al.; Blood 123, 3269 (2014)
Suppression of tumor angiogenesis by targeting the protein neddylation pathway: W.T. Yao, et al.; Cell Death Dis. 5, e1059 (2014)
MLN4924, a Novel NEDD8-activating enzyme inhibitor, exhibits antitumor activity and enhances cisplatin-induced cytotoxicity in human cervical carcinoma: in vitro and in vivo study: W.C. Lin, et al.; Am. J. Cancer Res. 5, 3350 (2015)
Broad and potent antiviral activity of the NAE inhibitor MLN4924: V.T. Le-Trilling, et al.; Sci. Rep. 6, 19977 (2016)
NEDD8-activating enzyme inhibitor, MLN4924 (Pevonedistat) induces NOXA-dependent apoptosis through up-regulation of ATF-4: X. Liu, et al.; BBRC 488, 1 (2017)
Targeting the protein ubiquitination machinery in melanoma by the NEDD8-activating enzyme inhibitor pevonedistat (MLN4924): K.M. Wong, et al.; Invest. New Drugs 35, 11 (2017)
Pevonedistat (MLN4924): mechanism of cell death induction and therapeutic potential in colorectal cancer: J. Ferris, et al.; Cell Death Discov. 6, 61 (2020)

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