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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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

(-)-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

PS 1145 dihydrochloride

PS-1145 (dihydrochloride) is a potent IκB kinase-2 inhibitor with an IC50 value of 88 nM. PS-1145 (dihydrochloride) inhibits activity of NF-κB by blocking IκB kinase phosphorylation in tumor-bearing rats[1].

  • CAS Number: 1049743-58-9
  • MF: C17H13Cl3N4O
  • MW: 395.670
  • Catalog: IKK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Protocatechuic acid methyl ester

Methyl 3,4-dihydroxybenzoate (Protocatechuic acid methyl ester;Methyl protocatechuate) is a major metabolite of antioxidant polyphenols found in green tea. Antioxidant and anti-inflammatory effect[1].

  • CAS Number: 2150-43-8
  • MF: C8H8O4
  • MW: 168.147
  • Catalog: Keap1-Nrf2
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 351.5±22.0 °C at 760 mmHg
  • Melting Point: 134-135°C
  • Flash Point: 148.5±15.8 °C

Mepazine hydrochloride

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

  • CAS Number: 2975-36-2
  • MF: C19H23ClN2S
  • MW: 346.91700
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: 444.4ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 222.6ºC

LY2409881

LY2409881 is a selective IκB kinase β (IKK2) inhibitor with an IC50 of 30 nM.

  • CAS Number: 946518-61-2
  • MF: C24H29ClN6OS
  • MW: 485.045
  • Catalog: IKK
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HPN-01

HPN-01 is a potent and selective IKK inhibitor, with pIC50 values of 6.4, 7.0 and <4.8 for IKK-α, IKK-β and IKK-ε, respectively. HPN-01 displays greater 50-fold selectivity over a panel of more than 50 other kinases, including ALK5, CDK-2, EGFR, ErbB2, GSK3β, PLK1, Src, and VEGFR-2[1].

  • CAS Number: 928655-63-4
  • MF: C19H16ClN3O3S
  • MW: 401.87
  • Catalog: IKK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Keap1-Nrf2-IN-3

Keap1-Nrf2-IN-3 is a KEAP1:NRF2 protein−protein interaction inhibitor, and with a Kd value of 2.5 nM for KEAP1 protein.

  • CAS Number: 2095066-47-8
  • MF: C31H34N6O3
  • MW: 538.64
  • Catalog: Keap1-Nrf2
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JSH-23

JSH-23 is an NF-κB inhibitor which inhibits NF-κB transcriptional activity with an IC50 of 7.1 μM.

  • CAS Number: 749886-87-1
  • MF: C16H20N2
  • MW: 240.343
  • Catalog: NF-κB
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 418.7±40.0 °C at 760 mmHg
  • Melting Point: 104.4-105.0℃
  • Flash Point: 245.0±30.9 °C

MALT1-IN-7

MALT1-IN-7 (compound 142b) is a potent MALT1 protease inhibitor. MALT1-IN-7 has the potential for cancer research[1].

  • CAS Number: 2178993-11-6
  • MF: C19H17F3N8O2S
  • MW: 478.45
  • Catalog: MALT1
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(R)-MALT1-IN-7

(R)-MALT1-IN-7 (compound 142a) is a potent MALT1 protease inhibitor. (R)-MALT1-IN-7 has the potential for cancer research[1].

  • CAS Number: 2178993-10-5
  • MF: C19H17F3N8O2S
  • MW: 478.45
  • Catalog: MALT1
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Antioxidant agent-5

Antioxidant agent-5 (compound D-6) is a potent antioxidant agent. Antioxidant agent-5 can inhibit oxLDL (oxidized low-density lipoprotein)-induced apoptosis and the expression of ICAM-1 and VCAM-1 in VECs. Antioxidant agent-5 suppresses oxLDL-induced increase of ROS level and nuclear translocation of NF-κB. Antioxidant agent-5 protects against oxLDL-induced endothelial injury by activating Nrf2/HO-1 anti-oxidation pathway[1].

  • CAS Number: 2684291-60-7
  • MF: C24H24N6O
  • MW: 412.49
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MSU38225

MSU38225 (MSU-38225) is a novel small molecule that inhibit the Nrf2 pathway, potentially inhibiting Nrf2 transcriptional activity and cancer cell growth;MSU38225 downregulates Nrf2 transcriptional activity and decreases the expression of Nrf2 downstream targets, including NQO1, GCLC, GCLM, AKR1C2, and UGT1A6.MSU38225 strikingly decreases the protein level of Nrf2, which can be blocked by the proteasome inhibitor MG132.Ubiquitination of Nrf2 is enhanced following treatment with MSU38225.By inhibiting production of antioxidants, MSU38225 increases the level of reactive oxygen species (ROS) when cells are stimulated with tert-butyl hydroperoxide (tBHP).MSU38225 also inhibits the growth of human lung cancer cells in both two-dimensional cell culture and soft agar.

  • CAS Number: 1629160-83-3
  • MF: C21H19N3
  • MW: 313.404
  • Catalog: Keap1-Nrf2
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bay 65-1942 (hydrochloride)

Bay 65-1942 hydrochloride is an ATP-competitive and selective IKKβ inhibitor.

  • CAS Number: 600734-06-3
  • MF: C22H26ClN3O4
  • MW: 431.91300
  • Catalog: IKK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Nrf2 activator-5

Nrf2 activator-5 (compound 1) is a potent Nrf2 activator that can attenuate H2O2-induced oxidative stress and LPS-stimulated inflammation in BV-2 microglial cells. Nrf2 activator-5 exhibits antioxidant and anti-inflammatory activities[1].

  • CAS Number: 1012860-13-7
  • MF: C25H30Cl2O6
  • MW: 497.41
  • Catalog: Keap1-Nrf2
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Keap1-Nrf2-IN-14

Keap1-Nrf2-IN-14 (compound 20c) is a KEAP1-NRF2 inhibitor that effectively disrupts the KEAP1-NRF2 interaction (IC50=75 nM) with a Kd value of 24 nM for KEAP1. Keap1-Nrf2-IN-14 induces the expression of NRF2 target genes and enhances the downstream antioxidant and anti-inflammatory activities. Keap1-Nrf2-IN-14 can be used in the study of oxidative stress-related inflammation[1].

  • CAS Number: 1928782-31-3
  • MF: C30H29NO8S
  • MW: 563.62
  • Catalog: Keap1-Nrf2
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ginsenoside Rh3

Ginsenoside Rh3 is a bacterial metabolite of Ginsenoside Rg5. Ginsenoside Rh3 treatment in human retinal cells induces Nrf2 activation.

  • CAS Number: 105558-26-7
  • MF: C36H60O7
  • MW: 604.857
  • Catalog: Keap1-Nrf2
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 695.0±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 374.1±31.5 °C

Desfluoro-ezetimibe

Desfluoro-ezetimibe is a desfluoro impurity of Ezetimibe. Ezetimibe is a potent, metabolically stable cholesterol absorption inhibitor. Ezetimibe is a Niemann-Pick C1-like1 (NPC1L1) inhibitor, and is a potent Nrf2 activator[1][2].

  • CAS Number: 302781-98-2
  • MF: C24H22FNO3
  • MW: 391.435
  • Catalog: Autophagy
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 642.8±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 342.6±31.5 °C

1,3-Diphenylpropane-1,3-dione

Dibenzoylmethane, a minor ingredient in licorice, activates Nrf2 and prevents various cancers and oxidative damage. Dibenzoylmethane, an analog of curcumin, results in dissociation from Keap1 and nuclear translocation of Nrf2[1].

  • CAS Number: 120-46-7
  • MF: C15H12O2
  • MW: 224.255
  • Catalog: Keap1-Nrf2
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 357.4±0.0 °C at 760 mmHg
  • Melting Point: 77-79 °C(lit.)
  • Flash Point: 146.9±20.2 °C

PS-1145

PS-1145 is an IκB kinase (IKK) inhibitor with an IC50 of 88 nM.

  • CAS Number: 431898-65-6
  • MF: C17H11ClN4O
  • MW: 322.748
  • Catalog: IKK
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 511.0±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 262.9±30.1 °C

IKK-16

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

  • CAS Number: 873225-46-8
  • MF: C28H29N5OS
  • MW: 483.628
  • Catalog: LRRK2
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 721.6±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 390.2±35.7 °C

(5-PHENYL-2-UREIDO)THIOPHENE-3-CARBOXAMIDE

IKK2-IN-4 (compound 4) is a potent IKK-2 inhibitor, with an IC50 of 25 nM. IKK2-IN-4 can inhibit the LPS-induced production of TNFα in PBMCs[1].

  • CAS Number: 354811-10-2
  • MF: C12H11N3O2S
  • MW: 261.30
  • Catalog: IKK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PF 184

PF-184 is a potent inhibitory factor-κB kinase 2 (IKK-2) inhibitor with an IC50 of 37 nM. PF-184 has anti-inflammatory effects[1].

  • CAS Number: 1187460-81-6
  • MF: C32H32ClFN6O4
  • MW: 619.09
  • Catalog: IKK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BI 605906

BI605906 is a novel IKKβ inhibitor with an IC50 value of 380 nM when assayed at 0.1 mM ATP.

  • CAS Number: 960293-88-3
  • MF: C17H22F2N4O3S2
  • MW: 432.50800
  • Catalog: IKK
  • Density: 1.48±0.1 g/cm3 (20 °C, 760 mmHg)
  • Boiling Point: 713.7±60.0 °C (760 mmHg)
  • Melting Point: N/A
  • Flash Point: N/A

Pyridoxine hydrochloride

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.

  • CAS Number: 58-56-0
  • MF: C8H12ClNO3
  • MW: 205.639
  • Catalog: Keap1-Nrf2
  • Density: N/A
  • Boiling Point: 491.9ºC at 760 mmHg
  • Melting Point: 214-215 °C(lit.)
  • Flash Point: 251.3ºC

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

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

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

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

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