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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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

sulfasalazine

Sulfasalazine is a drug for the treatment of rheumatoid arthritis and ulcerative colitis. Sulfasalazine is reported to suppress NF-κB activity.

  • CAS Number: 599-79-1
  • MF: C18H14N4O5S
  • MW: 398.393
  • Catalog: Autophagy
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 689.3±65.0 °C at 760 mmHg
  • Melting Point: 260-265 °C (dec.)(lit.)
  • Flash Point: 370.7±34.3 °C

BMS-345541

BMS-345541 is a selective inhibitor of the catalytic subunits of IKK (IKK-2 IC50=0.3 μM, IKK-1 IC50=4 μM). BMS-345541 binds at an allosteric site of IKK.

  • CAS Number: 547757-23-3
  • MF: C14H18ClN5
  • MW: 291.779
  • Catalog: IKK
  • Density: N/A
  • Boiling Point: 449.5ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 225.6ºC

MALT1-IN-6

MALT1-IN-6 is a potent MALT1 protease inhibitor with a Ki of 9 nM. MALT1-IN-6 has anticancer effects (WO2018226150A1; Compound 4)[1].

  • CAS Number: 2254669-07-1
  • MF: C18H12Cl2F3N9O
  • MW: 498.25
  • Catalog: MALT1
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NK 252

NK-252 is a potential Nrf2 activator, which exhibits a great Nrf2-activating potential.

  • CAS Number: 1414963-82-8
  • MF: C13H11N5O3
  • MW: 285.25800
  • Catalog: Keap1-Nrf2
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Antroquinonol

Antroquinonol ((+)-Antroquinonol), a ubiquinone derivative from the mushroom Antrodia camphorata, has hepatoprotective, anti-inflammatory, and anti-cancer effects[1]. Antroquinonol can be used for the research of colon cancer[2]. Antroquinonol reduces oxidative stress by enhancing the Nrf2 signaling pathway and inhibits inflammation and sclerosis in focal segmental glomerulosclerosis mice[3].

  • CAS Number: 1010081-09-0
  • MF: C24H38O4
  • MW: 390.56
  • Catalog: Keap1-Nrf2
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

tert-Butylhydroquinone

TBHQ is an antioxidant that activates Nrf2.

  • CAS Number: 1948-33-0
  • MF: C10H14O2
  • MW: 166.217
  • Catalog: Autophagy
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 291.4±20.0 °C at 760 mmHg
  • Melting Point: 127-129 °C(lit.)
  • Flash Point: 138.7±16.4 °C

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

MRT67307 hydrochloride

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

  • CAS Number: 2095432-39-4
  • MF: C26H37ClN6O2
  • MW: 501.06
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Baicalin

Baicalin is a flavonoid glycoside isolated from Scutellaria baicalensis. Baicalin reduces the expression of NF-κB.

  • CAS Number: 21967-41-9
  • MF: C21H18O11
  • MW: 446.361
  • Catalog: Autophagy
  • Density: 1.7±0.1 g/cm3
  • Boiling Point: 836.6±65.0 °C at 760 mmHg
  • Melting Point: 202-205 ºC
  • Flash Point: 297.2±27.8 °C

Bay 11-7085

BAY 11-7085 is an inhibitor of NF-κB activation and phosphorylation of IκBα; it stabilizes IκBα with an IC50 of 10 μM.

  • CAS Number: 196309-76-9
  • MF: C13H15NO2S
  • MW: 249.329
  • Catalog: NF-κB
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 407.1±45.0 °C at 760 mmHg
  • Melting Point: 80-82℃
  • Flash Point: 200.0±28.7 °C

Nrf2 activator-4

Nrf2 activator-4 (Compound 20a) is a highly potent, orally active Nrf2 activator with an EC50 of 0.63 µM. Nrf2 activator-4 suppresses reactive oxygen species against oxidative stress in microglia. Nrf2 activator-4 effectively recovers the learning and memory impairment in a scopolamine-induced mouse model[1].

  • CAS Number: 2383016-68-8
  • MF: C23H24ClF3N2O3
  • MW: 468.90
  • Catalog: Keap1-Nrf2
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Malachite green oxalate

Malachite green oxalate is a triphenylmethane dye which can be used to detect the release of phosphate in enzymatic reactions. Malachite green oxalate is also a potent and selective inhibitor of IKBKE, and inhibits its downstream targets such as IκBα, p65 and IRF3. Malachite green oxalate exhibits antitumor activity in vitro and in vivo[1][2][3].

  • CAS Number: 2437-29-8
  • MF: C52H54N4O12
  • MW: 454.946
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 164°C (dec.)
  • Flash Point: N/A

microcystin LY

Microcystin-LY, a cyclic heptapeptide toxin from the cyanobacterium Microcystis aeruginosa[2], acts as an activator of the Nrf2 pathway to induce oxidative stress response, and the induction effect is most obvious at 3μM.[1].

  • CAS Number: 123304-10-9
  • MF: C52H71N7O13
  • MW: 1002.16
  • Catalog: Keap1-Nrf2
  • Density: 1.28g/cm3
  • Boiling Point: 1310.2ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 746.2ºC

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

Eriodictyol

Eriodictyol is a flavonoid isolated from the Chinese herb, with antioxidant and anti-inflammatory activity. Eriodictyol induces Nrf2 signaling pathway.

  • CAS Number: 552-58-9
  • MF: C15H12O6
  • MW: 288.252
  • Catalog: Keap1-Nrf2
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 625.2±55.0 °C at 760 mmHg
  • Melting Point: 270ºC
  • Flash Point: 241.9±25.0 °C

Chaetominine

Chaetominine is an alkaloidal metabolite. Chaetominine has cytotoxicity against human leukemia K562 and colon cancer SW1116 cell lines. Chaetominine reduces MRP1-mediated drug resistance via inhibiting PI3K/Akt/Nrf2 signaling pathway in K562/Adr human leukemia cells[1][2].

  • CAS Number: 918659-56-0
  • MF: C22H18N4O4
  • MW: 402.40
  • Catalog: Keap1-Nrf2
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 720.7±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 389.6±35.7 °C

Garcinone D

Garcinone D, a natural xanthone from mangosteen, promotes the proliferation of C17.2 neural stem cell. Garcinone D increases the protein levels of phosphorylated signal transducer and activator of transcription 3 (p-STAT3), Cyclin D1 and nuclear factor erythroid 2-related factor (Nrf2), heme oxygenase-1 (HO-1) in concentration- and time- dependent manners[1].

  • CAS Number: 107390-08-9
  • MF: C24H28O7
  • MW: 428.475
  • Catalog: STAT
  • Density: 1.304
  • Boiling Point: 674.2±55.0 °C at 760 mmHg
  • Melting Point: 202-204 ºC
  • Flash Point: 231.2±25.0 °C

(R)-MLT-985

(R)-MLT-985 (compound 11) is a potent MALT1 protease inhibitor with an IC50 of 3 nM. (R)-MLT-985 has an IC50 of 20 nM for MALT1-dependent IL-2 production in Jurkat cells. (R)-MLT-985 suppresses growth and aberrant CARD11/BCL10/MALT1 complex signaling in ABC-DLBCL cells[1].

  • CAS Number: 1832577-07-7
  • MF: C17H15Cl2N9O2
  • MW: 448.27
  • Catalog: MALT1
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JNJ-67856633

JNJ-67856633 is an orally active, first-in-class, potent, selective and allosteric MALT1 protease inhibitor. JNJ-67856633 in some cases lead to tumor stasis[1][2][3].

  • CAS Number: 2230273-76-2
  • MF: C20H11F6N5O2
  • MW: 467.32
  • Catalog: MALT1
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

6-Methylsulfinylhexyl Isothiocyanate

Hesperin is a bioactive ingredient present in Japanese horseradish (wasabi) and has been shown to be an Nrf2 activator.

  • CAS Number: 4430-35-7
  • MF: C8H15NOS2
  • MW: 205.34100
  • Catalog: Keap1-Nrf2
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cga-jk3

CGA-JK3 is an IkappaB kinase inhibitor in innate immune process.

  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

[D-Asp3]-Microcystin-LR

Microcystin-[D-Asp3]-LR/Microcystin A is a cyanotoxin. Microcystin-[D-Asp3]-LR/Microcystin A can activate Nrf2 and promote oxidative stress response. Microcystin-[D-Asp3]-LR/Microcystin A can also be used in toxicology research[1][2].

  • CAS Number: 120011-66-7
  • MF: C48H72N10O12
  • MW: 981.15
  • Catalog: Keap1-Nrf2
  • Density: 1.3g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

QNZ (EVP4593)

QNZ shows strong inhibitory effects on NF-κB transcriptional activation and TNF-α production with IC50s of 11 and 7 nM, respectively. EVP4593 is a neuroprotective inhibitor of SOC channel.

  • CAS Number: 545380-34-5
  • MF: C22H20N4O
  • MW: 356.420
  • Catalog: TNF Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 602.0±55.0 °C at 760 mmHg
  • Melting Point: 169-175ºC
  • Flash Point: 317.9±31.5 °C

(+)-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

ML 334

ML334 is a potent, cell permeable activator of NRF2 by inhibition of Keap1-NRF2 protein-protein interaction. ML334 binds to Keap1 Kelch domain with a Kd of 1 μM. ML334 stimulates NRF2 expression and nuclear translocation and induces antioxidant response elements (ARE) activity[1][2].

  • CAS Number: 1432500-66-7
  • MF: C26H26N2O5
  • MW: 446.50
  • Catalog: Keap1-Nrf2
  • Density: 1.354±0.06 g/cm3(Predicted)
  • Boiling Point: 693.1±55.0 °C(Predicted)
  • Melting Point: N/A
  • Flash Point: N/A

Plantainoside D

Plantainoside D shows ACE inhibitory activity with IC50 2.17 mM[1]. And plantainoside D is a promising IKK-β inhibitor[2].

  • CAS Number: 147331-98-4
  • MF: C29H36O16
  • MW: 640.59
  • Catalog: Angiotensin-converting Enzyme (ACE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Sappanone A

Sappanone A is a homoisoflavanone which exhibits anti-inflammatory effects via modulation of Nrf2 and NF-κB. Sappanone can attenuate allergic airway inflammation in Ovalbumin-induced asthma[1].

  • CAS Number: 102067-84-5
  • MF: C16H12O5
  • MW: 284.263
  • Catalog: Keap1-Nrf2
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 605.5±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 233.2±25.0 °C

Danshensu

Danshensu, an active ingredient of Salvia miltiorrhiza, shows wide cardiovascular benefit by activating Nrf2 signaling pathway.

  • CAS Number: 76822-21-4
  • MF: C9H10O5
  • MW: 198.17
  • Catalog: Autophagy
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 481.5±40.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 259.1±23.8 °C

(-)-DHMEQ

(–)-DHMEQ is a potent NF-κB inhibitor.

  • CAS Number: 287194-40-5
  • MF: C13H11NO5
  • MW: 261.23000
  • Catalog: NF-κB
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A