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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Keap1-Nrf2-IN-1

Keap1–Nrf2 IN-1 (compound35) is a Kelch-like ECH-associated protein 1-nuclear factor erythroid 2-related factor 2 (Keap1-Nrf2) protein-protein interaction inhibitor, and with an IC50 of 43 nM for Keap1 protein. Keap1–Nrf2 IN-1 (compound35) activates Nrf2-regulated cytoprotective response and antagonizes acetaminophen-induced liver injury both in cellular and in vivo models[1].

  • CAS Number: 2232112-72-8
  • MF: C24H24N2O7S
  • MW: 484.52
  • Catalog: Keap1-Nrf2
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ginsenoside Rg3

Ginsenoside Rg3 is the main component of Red ginseng. Ginsenoside Rg3 inhibits Na+ and hKv1.4 channel with IC50s of 32.2±4.5 and 32.6±2.2 μM, respectively. Ginsenoside Rg3 also inhibits Aβ levels, NF-κB activity, and COX-2 expression.

  • CAS Number: 14197-60-5
  • MF: C42H72O13
  • MW: 785.013
  • Catalog: COX
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 885.0±65.0 °C at 760 mmHg
  • Melting Point: 315-318°C
  • Flash Point: 489.0±34.3 °C

DMX-129

DMX-129 is an ΙΚΚε and TBK-1 inhibitor with IC50 values of <30 nM for both TBK1 and IKKε[1].

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

Z-VRPR-FMK(Z-Val-Arg-Pro-DL-Arg-FMK

Z-VRPR-FMK is an irreversible MALT1 protein inhibitor. Z-VRPR-FMK inhibits the growth and invasion of diffuse large B-cell lymphoma by inhibiting MALT1-induced NF-κB activation and MMP expression[1].

  • CAS Number: 1381885-28-4
  • MF: C84H140N14O18S
  • MW: 1666.158
  • Catalog: MALT1
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 1659.8±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 957.6±34.3 °C

Astilbin

Astilbin, a flavonoid compound, is isolated from the rhizome of Smilax glabra. Astilbin enhances NRF2 activation. Astilbin also suppresses TNF-α expression and NF-κB activation.

  • CAS Number: 29838-67-3
  • MF: C21H22O11
  • MW: 450.393
  • Catalog: TNF Receptor
  • Density: 1.7±0.1 g/cm3
  • Boiling Point: 801.1±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 282.9±27.8 °C

Ammonium 1-pyrrolidinedithiocarbamate

Pyrrolidinedithiocarbamate ammonium is a selective NF-κB inhibitor.

  • CAS Number: 5108-96-3
  • MF: C5H12N2S2
  • MW: 164.292
  • Catalog: NF-κB
  • Density: 1.264g/cm3
  • Boiling Point: 199.7ºC at 760 mmHg
  • Melting Point: 153-155 °C(lit.)
  • Flash Point: 74.6ºC

Pyridoxine-d5 hydrochloride

Pyridoxine-d5 (hydrochloride) is the deuterium labeled Pyridoxine hydrochloride[1]. Pyridoxine hydrochloride (Pyridoxol;Vitamin B6) is a pyridine derivative. Pyridoxine (Pyridoxol;Vitamin B6) exerts antioxidant effects in cell model of Alzheimer's disease via the Nrf-2/HO-1 pathway[2].

  • CAS Number: 82896-38-6
  • MF: C8H12ClNO3
  • MW: 205.63900
  • Catalog: Keap1-Nrf2
  • 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

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

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

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

[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

Dimethyl fumarate

Dimethyl fumarate is a nuclear factor (erythroid-derived)-like 2 (Nrf2) pathway activator and induces upregulation of antioxidant gene expression.

  • CAS Number: 624-49-7
  • MF: C6H8O4
  • MW: 144.125
  • Catalog: Keap1-Nrf2
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 193.0±0.0 °C at 760 mmHg
  • Melting Point: 102-106 °C(lit.)
  • Flash Point: 91.1±0.0 °C

Keap1-Nrf2-IN-13

Keap1-Nrf2-IN-13 is a Keap1-Nrf2 protein–protein interaction (PPI) inhibitor with an IC50 value of 0.15 μM. Keap1-Nrf2-IN-13 has strong binding affinities to the Keap1 protein by forming hydrogen bond with the key polar residues (Asn414, Arg415, Arg483, Gln530). Keap1-Nrf2-IN-13 can be used in the research of oxidative stress-related and inflammatory diseases, including pulmonary fibrosis, chronic obstructive pulmonary disorder (COPD) and cancers[1].

  • CAS Number: 2456294-92-9
  • MF: C28H32N2O10S2
  • MW: 620.69
  • Catalog: Keap1-Nrf2
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TBK1 PROTAC 1

A novel potent, selective TBK1 PROTAC with DC50 of 12 nM, selectively degrades TBK1 with excellent selectivity against a related kinase IKKε; a chemical tool to assess TBK1 as a target in mutant K-Ras cancer cells.

  • CAS Number: 2052306-13-3
  • MF: C53H74BrN9O9S
  • MW: 1093.179
  • Catalog: IKK
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AZD3264

AZD3264 is a selective IkB-kinase IKK2 inhibitor.

  • CAS Number: 1609281-86-8
  • MF: C21H23N5O4S
  • MW: 441.503
  • Catalog: IKK
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 614.2±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 325.2±31.5 °C

KI696

KI696 is a high affinity probe that disrupts the Keap1/NRF2 interaction.

  • CAS Number: 1799974-70-1
  • MF: C28H30N4O6S
  • MW: 550.63
  • Catalog: Keap1-Nrf2
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

R079

R079 (compound 17) is a selective, orally active Nrf2 activator. R079 increases Nrf2 translocation activity (EC50 = 32.41 μM). R079 can neutralize excess levels of reactive oxygen species through activating Nrf2. R079 has anti-inflammatory properties and can be used in multiple sclerosis research [1].

  • CAS Number: 2115659-62-4
  • MF: C11H11N3O3S
  • MW: 265.29
  • Catalog: Keap1-Nrf2
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Oxireno[c]phenanthro[1,2-d]pyran-3,8(3aH,4bH)-dione,1-(3-furanyl)-1,5,6,6a,7,10a,10b,11,12,12a-decahydro-5-hydroxy-4b,7,7,10a,12a-pentamethyl-,(1S,3aS,4aR,4bS,5R,6aR,10aR,10bR,12aS)-

7-Deacetylgedunin is an activator of Keap1/Nrf2/HO-1. 7-Deacetylgedunin alleviates mice mortality induced by LPS. 7-Deacetylgedunin inhibits Keap1 expression and suppresses macrophage proliferation. 7-Deacetylgedunin suppresses inflammation in vivo and in vitro[1].

  • CAS Number: 10314-90-6
  • MF: C26H32O6
  • MW: 440.52900
  • Catalog: Keap1-Nrf2
  • Density: 1.29g/cm3
  • Boiling Point: 596ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 314.2ºC

5,7-Dihydroxychromone

5,7-Dihydroxychromone, the extract of Cudrania tricuspidata, activates Nrf2/ARE signal and exerts neuroprotective effects against 6-hydroxydopamine (6-OHDA)-induced oxidative stress and apoptosis. 5,7-Dihydroxychromone inhibits the expression of activated caspase-3 and caspase-9 and cleaved PARP in 6-OHDA-induced SH-SY5Y cells[1].

  • CAS Number: 31721-94-5
  • MF: C9H6O4
  • MW: 178.141
  • Catalog: Arenavirus
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 399.4±42.0 °C at 760 mmHg
  • Melting Point: 232-273℃
  • Flash Point: 170.8±21.4 °C

Hydrangenol

Hydrangenol is an orally active antiphotoaging compound. It can be isolated from Hydrangea serrata leaves. Hydrangenol prevents wrinkle formation by reducing MMP and inflammatory cytokine expression and increasing moisturizing factors and antioxidant genes level[1].

  • CAS Number: 480-47-7
  • MF: C15H12O4
  • MW: 256.253
  • Catalog: COX
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 528.3±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 206.4±23.6 °C

TPNA10168

TPNA10168 is an Nrf-2 activator that activates the Keap1-Nrf2-ARE pathway. TPNA10168 is neuroprotective against oxidative stress-induced damage. TPNA10168 significantly reduces the transcription of inflammatory genes, including TNF-α, IL-1β, IL-6, and iNOS. TPNA10168 can be used in research on anti-inflammatory and neurological diseases[1].

  • CAS Number: 957942-34-6
  • MF: C9H9ClO2S2
  • MW: 248.75
  • Catalog: Keap1-Nrf2
  • Density: 1.54±0.1 g/cm3 (20 °C, 760 mmHg)
  • Boiling Point: 490.3±45.0 °C (760 mmHg)
  • Melting Point: N/A
  • Flash Point: N/A

(R)-MALT1-IN-3

(R)-MALT1-IN-3 (compound 121) is a potent MALT1 protease inhibitor with an IC50 of 20 nM. (R)-MALT1-IN-3 has IC50 of 60 nM, 40 nM for human IL6/IL10 in OCI-LY3 cells, respectively[1].

  • CAS Number: 2504229-61-0
  • MF: C21H19F3N8O2
  • MW: 472.42
  • Catalog: MALT1
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

2-Trifluoromethyl-2'-methoxychalcone

2-Trifluoromethyl-2'-methoxychalcone is a chalcone derivative. 2-Trifluoromethyl-2'-methoxychalcone is a potent Nrf2 activator. 2-Trifluoromethyl-2'-methoxychalcone can be used for oxidative stress and inflammation related diseases research[1].

  • CAS Number: 1309371-03-6
  • MF: C17H13F3O2
  • MW: 306.28
  • Catalog: Keap1-Nrf2
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 395.6±42.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 186.4±22.8 °C

TAT 14TFA

TAT-14 is a 14-mer peptide that acts as Nrf2 activator with an anti-inflammatory effect. TAT-14 has no effect on Nrf2 mRNA expression, but increases Nrf2 protein level due to targeting the Nrf2 binding site on Keap1[1].

  • CAS Number: 1362661-34-4
  • MF: C137H230N48O39
  • MW: 3173.59
  • Catalog: Keap1-Nrf2
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A