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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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

Tomatidine

Tomatidine acts as an anti-inflammatory agent by blocking NF-κB and JNK signaling.

  • CAS Number: 77-59-8
  • MF: C27H45NO2
  • MW: 415.652
  • Catalog: JNK
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 527.2±25.0 °C at 760 mmHg
  • Melting Point: 210.5℃
  • Flash Point: 272.7±23.2 °C

NXPZ-2

NXPZ-2 is an orally active Keap1-Nrf2 protein–protein interaction (PPI) inhibitor with a Ki value of 95 nM, EC50 value of 120 and 170 nM. NXPZ-2 can dose-dependently ameliorate Aβ[1-42]-Induced cognitive dysfunction, improve brain tissue pathological changes in Alzheimer’s disease (AD) mouse by increasing neuron quantity and function. NXPZ-2 can inhibit oxidative stress by increasing Nrf2 expression levels and promoting its cytoplasm to nuclear translocation, which is helpful for Keap1-Nrf2 PPI inhibitors and AD associated disease research[1].

  • CAS Number: 2254492-08-3
  • MF: C27H27N5O7S2
  • MW: 597.66
  • Catalog: Keap1-Nrf2
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

lucidone

Lucidone, an anti-inflammatory agent that can be isolated from the fruit of Lindera erythrocarpa Makino. Lucidone inhibits LPS-induced NO and PGE2 production in RAW 264.7 mouse macrophages. Lucidone also decreases TNF-α secretion, iNOS and COX-2 expression. Lucidone prevents NF-κB translocation and inhibits JNK and p38MAPK signals. Lucidone also has inhibitory activity against Dengue virus (DENV) (EC50=25 μM)[1][2].

  • CAS Number: 19956-53-7
  • MF: C15H12O4
  • MW: 256.253
  • Catalog: COX
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 489.6±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 188.6±22.2 °C

Artemisitene

Artemisitene, a natural derivative of Artemisinin, is a Nrf2 activator with antioxidant and anticancer activities. Artemisitene activates Nrf2 by decreasing Nrf2 ubiquitination and increasing its stability[1][2].

  • CAS Number: 101020-89-7
  • MF: C15H20O5
  • MW: 280.32
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 160-162°C (lit.)
  • 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

Nrf2 activator-6

Nrf2 activator-6, a tetrahydroisoquinoline compound, is a Nrf2 activator. Nrf2 activator-6 has an IC50 of 5 nM for inhibiting the Kelch domain-Nrf2 interaction (WO2021214470A1; Example 4)[1].

  • CAS Number: 2728780-74-1
  • MF: C31H37ClFN5O5
  • MW: 614.11
  • Catalog: Keap1-Nrf2
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

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

Methyllucidone

Methyllucidone is a neuroprotective agent and an antioxidant that can be isolated from Lindera erythrocarpa Makino. Methyllucidone inhibits the ROS production, and activates antioxidant signaling pathways that include Nrf-2 and PI3K[1].

  • CAS Number: 19956-54-8
  • MF: C16H14O4
  • MW: 270.280
  • Catalog: Keap1-Nrf2
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 514.0±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 231.0±30.2 °C

BOT-64

BOT-64 is an inhibitory κB (IκB) kinase β (IKKβ) inhibitor with an IC50 of 1 µM. BOT-64 blocks lipopolysaccharide-induced nuclear factor-κB activation and nuclear factor-κB-regulated inflammatory gene transcription[1].

  • CAS Number: 113760-29-5
  • MF: C15H15NO2S
  • MW: 273.35
  • Catalog: IKK
  • Density: 1.27±0.1 g/cm3
  • Boiling Point: 402.1±48.0 °C
  • Melting Point: N/A
  • Flash Point: N/A

Laquinimod

Laquinimod is a potent immunomodulator which prevents neurodegeneration and inflammation in the central nervous system.

  • CAS Number: 248281-84-7
  • MF: C19H17ClN2O3
  • MW: 356.80
  • Catalog: NF-κB
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 546.0±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 284.0±30.1 °C

IKKβ-IN-1

IKKβ-IN-1 is a potent and orally active IkappaB (IKK-β) inhibitor with IC50 of 0.20 μM. IKKβ-IN-1 can reduce PGE2 and TNF-α production in mouse macrophage cells. IKKβ-IN-1 has the ability to protect mice against septic shock induced mortality[1].

  • CAS Number: 2410423-31-1
  • MF: C31H30N4O4S
  • MW: 554.66
  • Catalog: IKK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

1-Dehydro-[10]-gingerdione

1-Dehydro-[10]-gingerdione directly inhibits IKKβ activity by targeting the activation loop of IKKβ, thus disrupting IKKβ-catalysed IκBα phosphorylation in macrophages stimulated with agonists. 1-Dehydro-[10]-gingerdione inhibits LPS-induced NF-κB transcriptional activity. 1-Dehydro-[10]-gingerdione has the potential for NF-κB-associated inflammation and autoimmune disorders research[1].

  • CAS Number: 136826-50-1
  • MF: C21H30O4
  • MW: 346.461
  • Catalog: IKK
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 495.2±40.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 166.3±20.8 °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

4-Hydroxyphenyl ethanol

Tyrosol is a derivative of phenethyl alcohol. Tyrosol attenuates pro-inflammatory cytokines from cultured astrocytes and NF-κB activation. Anti-oxidative and anti-inflammatory effects[1].

  • CAS Number: 501-94-0
  • MF: C8H10O2
  • MW: 138.16
  • Catalog: NF-κB
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 375.2±27.0 °C at 760 mmHg
  • Melting Point: 89-92 °C(lit.)
  • Flash Point: 180.7±23.7 °C

Mepazine

Mepazine (Pecazine) is a potent and selective MALT1 inhibitor. Mepazine inhibits GSTMALT1 full length and GSTMALT1 325-760 with IC50s of 0.83 and 0.42 μM, respectively. Mepazine affects viability of ABC-DLBCL cells by enhancing apoptosis[1].

  • CAS Number: 60-89-9
  • MF: C19H22N2S
  • MW: 310.45600
  • Catalog: Apoptosis
  • Density: 1.159 g/cm3
  • Boiling Point: 444.4ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 222.6ºC

CDDO-dhTFEA

CDDO-dhTFEA (RTA dh404) is a synthetic oleanane triterpenoid compound which potently activates Nrf2 and inhibits the pro-inflammatory transcription factor NF-κB[1]. CDDO-dhTFEA restores hypertension (MAP), increases Nrf2 and expression of its target genes, attenuates activation of NF-κB and transforming growth factor-β pathways, and reduces glomerulosclerosis, interstitial fibrosis and inflammation in the chronic kidney disease (CKD) rats[2].

  • CAS Number: 1191265-33-4
  • MF: C33H45F3N2O3
  • MW: 574.72
  • Catalog: Keap1-Nrf2
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

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

Brusatol

Brusatol, isolated from the Brucea javanica plant, inhibits Nrf2.

  • CAS Number: 14907-98-3
  • MF: C26H32O11
  • MW: 520.526
  • Catalog: Keap1-Nrf2
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 724.3±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 242.2±26.4 °C

(Rac)-BAY-985

(Rac)-BAY-985 (Compound Example 100.01) is a potent, ATP-competitive and selective TBK1 inhibitor with an IC50 of 1.5 nM. Antitumor efficacy[1].

  • CAS Number: 2101925-20-4
  • MF: C27H30F3N9O
  • MW: 553.58
  • Catalog: IKK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AEM1

NRF2 inhibitor AEM1 is a specific small molecule inhibitor of Nrf2 transcriptional activity in cancer cells, shows no activity against a panel of >100 kinases (including isoforms of PI3K, AKT, and PKC); broadly decreases the expression of Nrf2 controlled genes (HMOX1, GPX2), sensitizes A549 cells to various chemotherapeutic agents, and inhibits the growth of A549 cells in vitro and in vivo.

  • CAS Number: 1030123-90-0
  • MF: C20H14FN3O2S
  • MW: 379.408
  • Catalog: Keap1-Nrf2
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 582.1±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 305.9±30.1 °C

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

NF-κB-IN-1

NF-κB-IN-1, a 4-arylidene crucumin analogue, is a potent NF-κB signaling pathway inhibitor. NF-κB-IN-1 directly inhibits IKK to block NF-κB activation. NF-κB-IN-1 effectively inhibits the viability of lung cancer cells and attenuates the clonogenic activity of A549 cells[1].

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

MIND4-17

An inducer of NRF2 that selectively activates NRF2 signaling with CD value (The concentration that doubles the specific activity) of 0.18 uM; covalently modifies a critical stress-sensor cysteine (C151) of the E3 ligase substrate adaptor protein KEAP1, arrests KEAP/NRF2 complex in the closed conformation in live cells; potently represses the release of the proinflammatory cytokine IL-6 in primary mouse HD and WT microglia and astrocytes.

  • CAS Number: 345989-24-4
  • MF: C20H15N5O3S
  • MW: 405.430
  • Catalog: Keap1-Nrf2
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 667.5±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 357.5±34.3 °C

Resveratrol analog 1

Resveratrol analog 1 is an analog of Resveratrol (HY-16561), compound 48. Resveratrol is a natural polyphenolic phytoalexin that possesses anti-oxidant, anti-inflammatory, cardioprotective, and anti-cancer properties.

  • CAS Number: 861446-16-4
  • MF: C14H11FO2
  • MW: 230.23
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TBK1/IKKε-IN-2

TBK1/IKKε-IN-2 is a dual TBK1 and IKKε inhibitor.

  • CAS Number: 1292310-49-6
  • MF: C26H27N5O3
  • MW: 457.524
  • Catalog: IKK
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 727.2±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 393.6±35.7 °C

RTA-408

RTA-408 is an antioxidant inflammation modulator (AIM), which activates Nrf2 and suppresses nitric oxide (NO).

  • CAS Number: 1474034-05-3
  • MF: C33H44F2N2O3
  • MW: 554.711
  • Catalog: Keap1-Nrf2
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 662.0±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 354.2±31.5 °C