Home >> Research Area >>Others>>NAE>> MLN4924 HCl salt

MLN4924 HCl salt

NAE inhibitor CAS# 1160295-21-5

MLN4924 HCl salt

Catalog No. BCC1773----Order now to get a substantial discount!

Product Name & Size	Price	Stock
MLN4924 HCl salt:5mg	$112.00	In stock
MLN4924 HCl salt:10mg	$190.00	In stock
MLN4924 HCl salt:25mg	$448.00	In stock
MLN4924 HCl salt:50mg	$784.00	In stock

Molarity Calculator Dilution Calculator Send Mail Directly

Quality Control of MLN4924 HCl salt

Quality Control & MSDS

Purity: >98%

Number of papers citing our products

Chemical structure

3D structure

Chemical Properties of MLN4924 HCl salt

Cas No.	1160295-21-5	SDF	Download SDF
PubChem ID	66576990	Appearance	Powder
Formula	C21H26ClN5O4S	M.Wt	479.98
Type of Compound	N/A	Storage	Desiccate at -20°C
Synonyms	Pevonedistat hydrochloride
Solubility	DMSO : 100 mg/mL (208.34 mM; Need ultrasonic) H2O : 10 mg/mL (20.83 mM; Need ultrasonic)
Chemical Name	[(1S,2S,4R)-4-[4-[[(1S)-2,3-dihydro-1H-inden-1-yl]amino]pyrrolo[2,3-d]pyrimidin-7-yl]-2-hydroxycyclopentyl]methyl sulfamate;hydrochloride
SMILES	C1CC2=CC=CC=C2C1NC3=NC=NC4=C3C=CN4C5CC(C(C5)O)COS(=O)(=O)N.Cl
Standard InChIKey	HJKDNNXKYODZJI-BVMPOVDASA-N
Standard InChI	InChI=1S/C21H25N5O4S.ClH/c22-31(28,29)30-11-14-9-15(10-19(14)27)26-8-7-17-20(23-12-24-21(17)26)25-18-6-5-13-3-1-2-4-16(13)18;/h1-4,7-8,12,14-15,18-19,27H,5-6,9-11H2,(H2,22,28,29)(H,23,24,25);1H/t14-,15+,18-,19-;/m0./s1
General tips	For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it.
About Packaging	1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment.
Shipping Condition	Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request.

Biological Activity of MLN4924 HCl salt

Description

MLN4924 (hydrochloride) is a potent and selective NEDD8-activating enzyme (NAE) inhibitor, with IC50 of 4.7 nM.In Vitro:MLN4924 is a potent inhibitor of NAE (half-maximal inhibitory concentration (IC50=0.004 μM), and is selective relative to the closely related enzymes UAE, SAE, UBA6 and ATG7 (IC50=1.5, 8.2, 1.8 and >10 μM, respectively). MLN4924 treatment inhibits overall protein turnover in cultured HCT-116 cells. Treatment of HCT-116 cells with MLN4924 for 24 h results in a dose-dependent decrease of Ubc12-NEDD8 thioester and NEDD8-cullin conjugates, with an IC50 < 0.1 μM, resulting in a reciprocal increase in the abundance of the known CRL substrates CDT1, p27 and NRF2 (also known as NFE2L2), but not non-CRL substrates[1]. MLN4924 induces CLL cell apoptosis and circumvented stroma-mediated resistance. MLN4924 promotes induction of Bim and Noxa in the CLL cells leading to rebalancing of Bcl-2 family members toward the proapoptotic BH3-only proteins[2]. MLN4924 rapidly inhibits cullin 1 neddylation and remarkably suppressed growth and survival as well as migration in a dose-and time-dependent manner in gastric cancer cells, and significantly suppresses migration by transcriptionally activating E-cadherin and repressing MMP-9[3].In Vivo:MLN4924 (10, 30 or 60 mg/kg, s.c.) leads to a dose- and time-dependent increase in the steady state levels of NRF2 and CDT1 in HCT-116 tumour-bearing mice, and decreases NEDD8-cullin levels in normal mouse tissue as illustrated in mouse bone marrow cells. MLN4924 administered on a BID schedule at 30 and 60 mg/kg inhibits tumour growth with T/C values of 0.36 and 0.15, respectively[1].

References:
[1]. Soucy TA, et al. An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer. Nature. 2009 Apr 9;458(7239):732-6. [2]. J. Claire Godbersen, e tal. The Nedd8-Activating Enzyme Inhibitor MLN4924 Thwarts Microenvironment-Driven NF-κB Activation and Induces Apoptosis in Chronic Lymphocytic Leukemia B Cells. [3]. Lan H, et al. Neddylation inhibitor MLN4924 suppresses growth and migration of human gastric cancer cells. Sci Rep. 2016 Apr 11;6:24218.

Protocol

Kinase Assay [1]
A time-resolved fluorescence energy transfer assay format is used to measure the in vitro activity of NAE. The enzymatic reaction, containing 50 μL 50 mM HEPES, pH 7.5, 0.05% BSA, 5 mM MgCl2, 20 μM ATP, 250 μM glutathione, 10 nM Ubc12-GST, 75 nM NEDD8-Flag and 0.3 nM recombinant human NAE enzyme, is incubated at 24°C for 90 min in a 384-well plate, before termination with 25 μL of stop/detection buffer (0.1 M HEPES, pH 7.5, 0.05% Tween20, 20 mM EDTA, 410 mM KF, 0.53 nM Europium-Cryptate-labelled monoclonal Flag-M2-specific antibody and 8.125 μg/mL PHYCOLINK allophycocyanin (XL-APC)-labelled GST-specific antibody). After incubation for 2 h at 24°C, the plate is read on the LJL Analyst HT Multi-Mode instrument using a time-resolved fluorescence method. A similar assay protocol is used to measure other E1 enzymes.

Cell Assay [1]
HCT-116 cells grown in 6-well cell-culture dishes are treated with 0.1% DMSO (control) or MLN4924 for 24 h. Whole cell extracts are prepared and analysed by immunoblotting. For analysis of the E2-UBL thioester levels, lysates are fractionated by non-reducing SDS-PAGE and immunoblotted with polyclonal antibodies to Ubc12, Ubc9 and Ubc10. For analysis of other proteins, lysates are fractionated by reducing SDS-PAGE and probed with primary antibodies as follows: mouse monoclonal antibodies to CDT1, p27, geminin, ubiquitin, securin/PTTG and p53 or rabbit polyclonal antibodies to NRF2, Cyclin B1 and GADD34. Rabbit monoclonal antibodies to NEDD8 and phosphorylated CHK1 (Ser 317) are generated using Ac-KEIEIDIEPTDKVERIKERVEE-amide and Ac-VKYSS(pS)QPEPRT-amide as immunogens, respectively. Antibodies to pH3, cleaved PARP and cleaved caspase 3 are from Cell Signaling Technologies. Secondary HRP-labelled antibodies to rabbit IgG or mouse IgG are used as appropriate. Blots are developed with ECL reagent.

Animal Administration [1]
Female athymic NCR mice are used in all in vivo studies. Mice are inoculated with 2×106 HCT-116 cells (or 30-40 mg H522 tumour fragments) subcutaneously in the right flank, and tumour growth is monitored with caliper measurements. When the mean tumour volume reaches approximately 200 mm3, animals are dosed subcutaneously with vehicle (10% cyclodextrin) or MLN4924. Inhibition of tumour growth (T/C) is calculated on the last day of treatment.

MLN4924 HCl salt Dilution Calculator

Concentration (start)

Volume (start)

Concentration (final)

Volume (final)

C₁

V₁

C₂

V₂

calculate

MLN4924 HCl salt Molarity Calculator

calculate

Preparing Stock Solutions of MLN4924 HCl salt

	1 mg	5 mg	10 mg	20 mg	25 mg
1 mM	2.0834 mL	10.4171 mL	20.8342 mL	41.6684 mL	52.0855 mL
5 mM	0.4167 mL	2.0834 mL	4.1668 mL	8.3337 mL	10.4171 mL
10 mM	0.2083 mL	1.0417 mL	2.0834 mL	4.1668 mL	5.2086 mL
50 mM	0.0417 mL	0.2083 mL	0.4167 mL	0.8334 mL	1.0417 mL
100 mM	0.0208 mL	0.1042 mL	0.2083 mL	0.4167 mL	0.5209 mL
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations.

Organizitions Citing Our Products recently

Calcutta University

University of Minnesota

University of Maryland School of Medicine

University of Illinois at Chicago

The Ohio State University

University of Zurich

Harvard University

Colorado State University

Auburn University

Yale University

Worcester Polytechnic Institute

Washington State University

Stanford University

University of Leipzig

Universidade da Beira Interior

The Institute of Cancer Research

Heidelberg University

University of Amsterdam

University of Auckland

TsingHua University

The University of Michigan

Miami University

DRURY University

Jilin University

Fudan University

Wuhan University

Sun Yat-sen University

Universite de Paris

Deemed University

Auckland University

The University of Tokyo

Korea University

Background on MLN4924 HCl salt

MLN4924 is a potent and selective small molecule NEDD8-activating enzyme (NAE) inhibitor.

Description

Pevonedistat hydrochloride (MLN4924 hydrochloride) is a potent and selective NEDD8-activating enzyme (NAE) inhibitor, with an IC50 of 4.7 nM.

Keywords:

MLN4924 HCl salt,1160295-21-5,Pevonedistat hydrochloride,Natural Products,NAE, buy MLN4924 HCl salt , MLN4924 HCl salt supplier , purchase MLN4924 HCl salt , MLN4924 HCl salt cost , MLN4924 HCl salt manufacturer , order MLN4924 HCl salt , high purity MLN4924 HCl salt

MLN4924 HCl salt

Catalog No. BCC1773----Order now to get a substantial discount!

Catalog No.:BCC2091

CAS No.:1201902-80-8

Catalog No.:BCC1227

CAS No.:133407-82-6

Catalog No.:BCC1237

CAS No.:133407-86-0

Catalog No.:BCC1124

CAS No.:158442-41-2

Catalog No.:BCC3589

CAS No.:856849-35-9

Quality Control of MLN4924 HCl salt

Quality Control & MSDS

Number of papers citing our products

Chemical structure

3D structure

Chemical Properties of MLN4924 HCl salt

Biological Activity of MLN4924 HCl salt

Protocol

MLN4924 HCl salt Dilution Calculator

MLN4924 HCl salt Molarity Calculator

Preparing Stock Solutions of MLN4924 HCl salt

Organizitions Citing Our Products recently

Background on MLN4924 HCl salt

Catalog No.:BCC7729

CAS No.:1160247-92-6

Catalog No.:BCC8452

CAS No.:116-85-8

Catalog No.:BCC8680

CAS No.:116-63-2

Catalog No.:BCC5475

CAS No.:116-06-3

Catalog No.:BCC6244

CAS No.:1159996-20-9

Catalog No.:BCN7990

CAS No.:1159989-19-1

Catalog No.:BCN6041

CAS No.:1159913-80-0

Catalog No.:BCC1507

CAS No.:1159824-67-5

Catalog No.:BCN7282

CAS No.:1159753-88-4

Catalog No.:BCN6040

CAS No.:1159579-45-9

Catalog No.:BCN6039

CAS No.:1159579-44-8

Catalog No.:BCN6106

CAS No.:115939-25-8

Catalog No.:BCC7771

CAS No.:1160514-60-2

Catalog No.:BCN4818

CAS No.:116064-76-7

Catalog No.:BCN5357

CAS No.:116064-77-8

Catalog No.:BCC7841

CAS No.:1160927-48-9

Catalog No.:BCC6073

CAS No.:1160928-63-1

Catalog No.:BCC2756

CAS No.:1161-13-3

Catalog No.:BCC7673

CAS No.:1161-94-0

Catalog No.:BCC6058

CAS No.:1161002-05-6

Catalog No.:BCC4596

CAS No.:1161205-04-4

Catalog No.:BCN2459

CAS No.:20069-02-7

Catalog No.:BCN2054

CAS No.:116174-63-1

Catalog No.:BCN8213

CAS No.:116183-66-5

Description

Keywords:

Online Inquiry for:

Fill out the information below