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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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

TPCA-1

TPCA-1 is a potent and selective inhibitor of IKK-2 with IC50 of 17.9 nM.

  • CAS Number: 507475-17-4
  • MF: C12H10FN3O2S
  • MW: 279.290
  • Catalog: IKK
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 442.6±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 221.5±28.7 °C

4-Octyl Itaconate

4-Octyl Itaconate is a cell-permeable Itaconate derivative. Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1.

  • CAS Number: 3133-16-2
  • MF: C13H22O4
  • MW: 242.31
  • Catalog: Keap1-Nrf2
  • 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

MLT-985

MLT-985 is a highly selective allosteric MALT1 inhibitor with an IC50 value of 3 nM.

  • CAS Number: 1832576-25-6
  • MF: C17H15Cl2N9O2
  • MW: 448.27
  • Catalog: MALT1
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

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

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-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

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

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

ML385

ML385 is a specific nuclear factor erythroid 2-related factor 2 (NRF2) inhibitor with an IC50 of 1.9 μM.

  • CAS Number: 846557-71-9
  • MF: C29H25N3O4S
  • MW: 511.591
  • Catalog: Keap1-Nrf2
  • Density: 1.4±0.1 g/cm3
  • 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

(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

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

Keap1-Nrf2-IN-16

Keap1-Nrf2-IN-16 is a biological active peptide. (KEAP1 binding activity)

  • CAS Number: 1362661-40-2
  • MF: C73H114N16O26
  • MW: 1631.78
  • 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

Resveratrol

Resveratrol (SRT 501), a natural polyphenol that possesses anti-oxidant, anti-inflammatory, cardioprotective, and anti-cancer properties. It has a wide spectrum of targets including mTOR, JAK, β-amyloid.

  • CAS Number: 501-36-0
  • MF: C14H12O3
  • MW: 228.243
  • Catalog: Bacterial
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 449.1±14.0 °C at 760 mmHg
  • Melting Point: 253-255°C
  • Flash Point: 222.3±14.7 °C

PHA-408

PHA 408 (PHA-408) is a potent, selective and orally active IκB kinase-2 (IKK-2) inhibitor. PHA 408 is a powerful anti-inflammatory agent against lipopolysaccharide (LPS)- and cigarette smoke (CS)-mediated lung inflammation[1].

  • CAS Number: 503555-55-3
  • MF: C29H27ClFN7O2
  • MW: 560.02
  • Catalog: IKK
  • 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

Z-Val-Arg-Pro-DL-Arg-fluoromethylketone trifluoroacetate salt

Val-Arg-Pro-DL-Arg-Fluoromethylketone is a potent MALT1 inhibitor. Val-Arg-Pro-DL-Arg-Fluoromethylketone inhibits cell proliferation and migration. Val-Arg-Pro-DL-Arg-Fluoromethylketone shows anticancer activity[1].

  • CAS Number: 1926163-57-6
  • MF: C31H49FN10O6
  • MW: 676.78
  • Catalog: MALT1
  • Density: 1.4±0.1 g/cm3
  • 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

CDDO-Im

CDDO-Im (CDDO-imidazolide) is an activator of Nrf2 and PPAR, with Kis of 232 and 344 nM for PPARα and PPARγ.

  • CAS Number: 443104-02-7
  • MF: C34H43N3O3
  • MW: 541.72400
  • Catalog: PPAR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

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

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

4'-Hydroxywogonin

4′-Hydroxywogonin (8-Methoxyapigenin), a flavonoid, could be isolated from a variety of plants including Scutellaria barbata and Verbena littoralis. 4′-Hydroxywogonin has anti-inflammatory activity via TAK1/IKK/NF-κB, MAPKs and PI3/AKT signaling pathways. 4′-Hydroxywogonin inhibits angiogenesis by disrupting PI3K/AKT signaling. 4′-Hydroxywogonin inhibits cell proliferation and induces apoptosis[1][2][3].

  • CAS Number: 57096-02-3
  • MF: C16H12O6
  • MW: 300.263
  • Catalog: Apoptosis
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 578.1±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 220.9±23.6 °C

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