Rel/NF-κB proteins are dimeric, DNA sequence-specific transcription factors that coordinate inflammatory responses; innate and adaptive immunity; and cellular differentiation, proliferation, and survival in almost all multicellular organisms. In most cells NF-κB exists in the cytoplasm in an inactive complex bound to IkappaB. The NF-κB network consists of five family member protein monomers (p65/RelA, RelB, cRel, p50, and p52) that form homodimers or heterodimers that bind DNA differentially and are regulated by two pathways: the canonical, NF-κB essential modulator (NEMO)-dependent pathway and the noncanonical, NEMO-independent pathway.

The I Bs bind to NF-κB dimers and sterically block the function of their NLSs, thereby causing their cytoplasmic retention. Potent NF-κB activators, such as TNFα and IL-1, cause almost complete degradation of IκBs (especially I B ) by the 26S proteasome, and NF-κB is activated and enters the nucleus. Nfkb2/p100 is the primary signaling node at which canonical and noncanonical signals interact. NIK/IKK1 processes p100 into p52, enabling the activity of RelB, NIK degrades IκBδ, allowing for sustained RelA activity, and canonical pathway activity may boost noncanonical pathway activation of RelB:p52.

Activation of the NF-κB pathway is involved in the pathogenesis of chronic inflammatory diseases, such as asthma, rheumatoid arthritis, and inflammatory bowel disease. In addition, altered NF-κB regulation may be involved in other diseases such as atherosclerosis and Alzheimer’s disease and a variety of human cancers. Therefore, numerous drugs, natural products, and normal or recombinant proteins that inhibits NF-κB activation can used in the treatment of NF-κB-related diseases.

References:
[1] Karin M. Oncogene. 1999 Nov 22;18(49):6867-74.
[2] Yamamoto Y, et al. J Clin Invest. 2001 Jan;107(2):135-42.
[3] Mitchell S, et al. Wiley Interdiscip Rev Syst Biol Med. 2016 May;8(3):227-41.


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Dimethyl Fumarate-2,3-d2

Dimethyl fumarate-d2 is the deuterium labeled Dimethyl fumarate[1]. Dimethyl fumarate (DMF) is an orally active and brain-penetrant Nrf2 activator and induces upregulation of antioxidant gene expression. Dimethyl fumarate induces necroptosis in colon cancer cells through GSH depletion/ROS increase/MAPKs activation pathway, and also induces cell autophagy. Dimethyl fumarate can be used for multiple sclerosis research[2][3].

  • CAS Number: 23057-98-9
  • MF: C6H6D2O4
  • MW: 146.138
  • Catalog: HIV
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 193.0±0.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 91.1±0.0 °C

Dimethyl fumarate d6

Dimethyl fumarate D6 is a deuterium labeled Dimethyl fumarate. Dimethyl fumarate is a nuclear factor (erythroid-derived)-like 2 (Nrf2) pathway activator and induces upregulation of antioxidant gene expression[1][2][3][4][5][6].

  • CAS Number: 66487-95-4
  • MF: C6H2D6O4
  • MW: 150.162290668
  • Catalog: Keap1-Nrf2
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Aurin

Rosolic Acid is an activator of Nrf2, as well as its downstream targets. Rosolic Acid increases the levels of angiogenic factors, decreases inflammation (TNF-α and IL-1β) and apoptotic markers (CXCL10 and CCL2). Rosolic Acid restores the function of pancreatic cells and protects endothelial cells (ECs) from endoplasmic reticulum stressed[1].

  • CAS Number: 603-45-2
  • MF: C19H14O3
  • MW: 290.31
  • Catalog: Keap1-Nrf2
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 543.0±50.0 °C at 760 mmHg
  • Melting Point: ca. 308ºC (decomposes)
  • Flash Point: 296.2±26.6 °C

MRT67307

MRT67307 is a dual inhibitor of the IKKε and TBK-1 with IC50s of 160 and 19 nM, respectively. MRT67307 also inhibits ULK1 and ULK2 with IC50s of 45 and 38 nM, respectively.

  • CAS Number: 1190378-57-4
  • MF: C26H36N6O2
  • MW: 464.603
  • Catalog: Autophagy
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BMS-066

BMS-066 is an IKKβ/Tyk2 pseudokinase inhibitor, with IC50s of 9 nM and 72 nM, respectively.

  • CAS Number: 914946-88-6
  • MF: C19H21N7O2
  • MW: 379.41600
  • Catalog: IKK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Amlexanox

AmLexanox is a specific inhibitor of IKKε and TBK1, and inhibits the IKKε and TBK1 activity determined by MBP phosphorylation with an IC50 of approximately 1-2 μM.

  • CAS Number: 68302-57-8
  • MF: C16H14N2O4
  • MW: 298.293
  • Catalog: IKK
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 570.0±50.0 °C at 760 mmHg
  • Melting Point: >3000C
  • Flash Point: 298.5±30.1 °C

Bardoxolone Methyl

Bardoxolone is a synthetic triterpenoid compound with potential antineoplastic and anti-inflammatory activities, acting as an activator of the Nrf2 pathway and an inhibitor of the NF-κB pathway.

  • CAS Number: 218600-53-4
  • MF: C32H43NO4
  • MW: 505.688
  • Catalog: Autophagy
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 600.8±55.0 °C at 760 mmHg
  • Melting Point: 215-223 °C
  • Flash Point: 256.5±21.7 °C

Curcumin D6

Curcumin D6 (Diferuloylmethane D6) is a deuterium labeled Curcumin (Turmeric yellow). Curcumin (Turmeric yellow) is a natural phenolic compound with diverse pharmacologic effects including anti-inflammatory, antioxidant, antiproliferative and antiangiogenic activities. Curcumin is an inhibitor of p300 histone acetylatransferase (HATs) and also shows inhibitory effects on NF-κB and MAPKs.

  • CAS Number: 1246833-26-0
  • MF: C21H14D6O6
  • MW: 374.41700
  • Catalog: Influenza Virus
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

IMD 0354

IMD-0354 is a selective IKKβ inhibitor which inhibits NF-κB activity. IMD0354 inhibits TNF-α induced NF-κB transcription activity with an IC 50 of 1.2±0.3 uM.

  • CAS Number: 978-62-1
  • MF: C15H8ClF6NO2
  • MW: 383.67300
  • Catalog: IKK
  • Density: 1.561g/cm3
  • Boiling Point: 323.1ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 149.2ºC

(6aS,11bR)-6a,11b-Dihydro-5,6a,9-trihydroxy-2,2-dimethyl-11b-(3-methyl-2-butenyl)-2H,6H-benzofuro[3,2-b]pyrano[3,2-g][1]benzopyran-6-one

Sanggenon A (Sanggenone A) exerts anti-inflammatory effects by regulating NF-κB and HO-1/Nrf2 signaling pathways in BV2 and RAW264.7 cells. Sanggenon A markedly inhibits the Lipopolysaccharide (LPS; HY-D1056)-induced production of nitric oxide[1].

  • CAS Number: 76464-71-6
  • MF: C25H24O7
  • MW: 436.45
  • Catalog: Keap1-Nrf2
  • Density: 1.397g/cm3
  • Boiling Point: 668.8ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 231.6ºC

Ezetimibe

Ezetimibe (SCH 58235) is a Niemann-Pick C1-like1 (NPC1L1) inhibitor, and is a potent Nrf2 activator. Ezetimibe (SCH 58235) is a potent cholesterol absorption inhibitor.

  • CAS Number: 163222-33-1
  • MF: C24H21F2NO3
  • MW: 409.425
  • Catalog: Autophagy
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 654.9±55.0 °C at 760 mmHg
  • Melting Point: 164-166℃
  • Flash Point: 349.9±31.5 °C

Dihydroartemisinin

Dihydroartemisinin is a potent anti-malaria agent.

  • CAS Number: 71939-50-9
  • MF: C15H24O5
  • MW: 284.348
  • Catalog: Autophagy
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 375.6±42.0 °C at 760 mmHg
  • Melting Point: 144-149ºC
  • Flash Point: 181.0±27.9 °C

Secoisolariciresinol Diglucoside

seco-Isolariciresinol Diglucoside, a synthetic lignin, which is derived from the natural plant flaxseed. seco-Isolariciresinol Diglucoside reduces asbestos-induced NLRP3 expression, and NF-κB activation in macrophages (MF). seco-Isolariciresinol Diglucoside also activates Nrf2.

  • CAS Number: 148244-82-0
  • MF: C32H50O18
  • MW: 722.73
  • Catalog: NOD-like Receptor (NLR)
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 989.2±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 552.0±34.3 °C

Ezetimibe-d4

Ezetimibe-d4 is deuterium labeled Ezetimibe. Ezetimibe (SCH 58235) is a potent cholesterol absorption inhibitor. Ezetimibe is a Niemann-Pick C1-like1 (NPC1L1) inhibitor, and is a potent Nrf2 activator.

  • CAS Number: 1093659-89-2
  • MF: C24H17D4F2NO3
  • MW: 413.45
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Rocaglamide

Rocaglamide is a potent NF-κB activation inhibitor.

  • CAS Number: 84573-16-0
  • MF: C29H31NO7
  • MW: 505.559
  • Catalog: NF-κB
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 667.3±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 357.4±31.5 °C

MI 2

MI 2 (MALT1 inhibitor) is an irreversible MALT1 protease inhibitor with an IC50 of 5.84 μM.

  • CAS Number: 1047953-91-2
  • MF: C19H17Cl3N4O3
  • MW: 455.72200
  • Catalog: MALT1
  • Density: 1.44±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CAY10575

IKK2-IN-3 (Compound 8) is an IKK2 inhibitor with an IC50 of 0.075 μM[1].

  • CAS Number: 916985-21-2
  • MF: C22H21N3O6S2
  • MW: 487.549
  • Catalog: IKK
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 735.4±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 398.5±35.7 °C

Pyridoxine

Pyridoxine is a pyridine derivative. Pyridoxine exerts antioxidant effects in cell model of Alzheimer's disease via the Nrf-2/HO-1 pathway.

  • CAS Number: 65-23-6
  • MF: C8H11NO3
  • MW: 169.178
  • Catalog: Keap1-Nrf2
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 491.9±40.0 °C at 760 mmHg
  • Melting Point: 159-162ºC
  • Flash Point: 251.3±27.3 °C

MRT67307 dihydrochloride

MRT67307 dihydrochloride is a dual inhibitor of the IKKε and TBK-1 with IC50s of 160 and 19 nM, respectively[1]. MRT67307 dihydrochloride also inhibits ULK1 and ULK2 with IC50s of 45 and 38 nM, respectively. MRT67307 dihydrochloride also blocks autophagy in cells[2].

  • CAS Number: 1781882-89-0
  • MF: C26H38Cl2N6O2
  • MW: 537.52
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tanshindiol C

Tanshindiol C is a S-adenosylmethionine-competitive EZH2 (Histone Methyltransferase) inhibitor with an IC50 of 0.55 μM for inhibiting the methyltransferase activity. Tanshindiol C is also an activator of both Nrf2 and Sirtuin 1 (Sirt1) in macrophages. Tanshindiol C possesses anti-cancer activity, and can be used for atherosclerosis research[1][2].

  • CAS Number: 97465-71-9
  • MF: C18H16O5
  • MW: 312.317
  • Catalog: Sirtuin
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 561.5±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 293.4±30.1 °C

Keap1-Nrf2-IN-12

Keap1-Nrf2-IN-12 is a potent Keap1-Nrf2 inhibitor with an IC50 value of 2.30 µM. Keap1-Nrf2-IN-12 shows metabolic stability in human liver microsomes[1].

  • CAS Number: 2250082-04-1
  • MF: C26H28N2O10S2
  • MW: 592.64
  • Catalog: Keap1-Nrf2
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Nrf2-IN-1

Nrf2-IN-1 (Compound 4f) is an inhibitor of nuclear factor-erythroid 2-related factor 2 (Nrf2), acts as a promising agent in acute myeloid leukemia (AML) therapy[1].

  • CAS Number: 1610022-76-8
  • MF: C21H22ClN3O2
  • MW: 383.87
  • Catalog: Keap1-Nrf2
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Curcumin

Curcumin is a natural phenolic compound with diverse pharmacologic effects including anti-inflammatory, antioxidant, antiproliferative and antiangiogenic activities. Curcumin is an inhibitor of p300 histone acetylatransferase ((HATs)) and also shows inhibitory effects on NF-κB and MAPKs.

  • CAS Number: 458-37-7
  • MF: C21H20O6
  • MW: 368.380
  • Catalog: Autophagy
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 593.2±50.0 °C at 760 mmHg
  • Melting Point: 183 °C
  • Flash Point: 209.7±23.6 °C

(R)-5-Hydroxy-1,7-diphenylheptan-3-one

(R)-5-Hydroxy-1,7-diphenyl-3-heptanone is a diarylheptanoid that can be found in Alpinia officinarum. (R)-5-Hydroxy-1,7-diphenyl-3-heptanone ameliorates oxidative stress and insulin resistance via activation of Nrf2/ARE pathway[1].

  • CAS Number: 100761-20-4
  • MF: C19H22O2
  • MW: 282.38
  • Catalog: Keap1-Nrf2
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 473.8±33.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 201.4±18.0 °C

DDO-7263

DDO-7263, a 1,2,4-Oxadiazole derivative, is a potent Nrf2 activator. DDO-7263 upregulates Nrf2 through binding to Rpn6 to block the assembly of 26S proteasome and the subsequent degradation of ubiquitinated Nrf2. DDO-7263 activates the Nrf2-ARE signaling pathway and exerts anti-inflammatory activity[1].

  • CAS Number: 2254004-96-9
  • MF: C14H9F2N3O
  • MW: 273.24
  • Catalog: Keap1-Nrf2
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

K67

K67 is a specific inhibitor of the interaction between S349-phosphorylated p62 and Keap1, exhibts no inhibitory effect on the interaction of full-length Keap1 with Nrf2-ETGE or full-length Nrf2; has specific inhibitory effect on the Nrf2 target genes, dramatically suppresses the proliferations of Huh1 cells and of Huh7 cells expressing phospho-mimetic p62.

  • CAS Number: 2046250-48-8
  • MF: C29H30N2O7S2
  • MW: 582.688
  • Catalog: Keap1-Nrf2
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 752.2±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 408.7±35.7 °C

NIK SMI1

NIK SMI1 is a potent, selective NF-κB inducing kinase (NIK) inhibitor, which inhibits NIK-catalyzed hydrolysis of ATP to ADP with IC50 of 0.23±0.17 nM.

  • CAS Number: 1660114-31-7
  • MF: C20H19N3O4
  • MW: 365.38
  • Catalog: NF-κB
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Shikonine

Shikonin is a major component of a Chinese herbal medicine named zicao. Shikonin has shown various biological activities, including inhibition of TNF-α, NF-κB, HIV-1.

  • CAS Number: 517-89-5
  • MF: C16H16O5
  • MW: 288.295
  • Catalog: TNF Receptor
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 567.4±50.0 °C at 760 mmHg
  • Melting Point: 147ºC
  • Flash Point: 311.0±26.6 °C

IKK-16

IKK 16 hydrochloride is a selective IκB kinase (IKK) inhibitor for IKK2, IKK complex and IKK1 with IC50s of 40 nM, 70 nM and 200 nM, respectively[1]. IKK16 also inhibits leucine-rich repeat kinase-2 (LRRK2) with an IC50 of 50 nM[2].

  • CAS Number: 1186195-62-9
  • MF: C28H30ClN5OS
  • MW: 520.09
  • Catalog: LRRK2
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(+)-DHMEQ

(+)-DHMEQ is an activator of antioxidant transcription factor Nrf2. (+)-DHMEQ is the enantiomer of (-)-DHMEQ. (-)-DHMEQ inhibits NF-kB than its enantiomer (+)-DHMEQ.

  • CAS Number: 287194-41-6
  • MF: C13H11NO5
  • MW: 261.230
  • Catalog: Keap1-Nrf2
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 617.2±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 327.1±31.5 °C