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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Pterisolic acid B

Pterisolic acid B (Compound 2) is an ent-Kaurane diterpenoid. Pterisolic acid B can be isolated from fern Pteris semipinnata (Pteridaceae)[1].

  • CAS Number: 1401419-86-0
  • MF: C20H26O4
  • MW: 330.418
  • Catalog: Keap1-Nrf2
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 536.6±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 292.4±26.6 °C

GS143

GS143 is a selec­tive IκBα ubiquitination inhibitor with an IC50 of 5.2 μM for SCFβTrCP1-mediated IκBα ubiquitylation. GS143 sup­presses NF-κB acti­va­tion and tran­scrip­tion of tar­get genes and does not inhibit proteasome activity. GS143 has anti-asthma effect[1][2].

  • CAS Number: 916232-21-8
  • MF: C28H19FN2O4
  • MW: 466.5
  • Catalog: E1/E2/E3 Enzyme
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MLN120B

MLN120B is a specific, ATP competitive IKKβ inhibitor with an IC50 of 60 nM.

  • CAS Number: 783348-36-7
  • MF: C19H15ClN4O2
  • MW: 366.801
  • Catalog: IKK
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 545.0±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 283.4±30.1 °C

dehydrobruceine B

Dehydrobruceine B, a quassinoid, can be isolated from Brucea javanica. Dehydrobruceine B shows a synergistic effect with Cisplatin (HY-17394) to induce apoptosis via mitochondrial method. Dehydrobruceine B increases apoptosis-inducing factor (AIF) and Bax expression and suppresses Keap1-Nrf2[1].

  • CAS Number: 53730-90-8
  • MF: C23H26O11
  • MW: 478.45
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

RGT-068A

RGT-068A is a potent, selective and oral bioavailable MALT1 inhibitor[1].

  • CAS Number: 2577171-33-4
  • MF: C17H16ClN9O2
  • MW: 413.82
  • Catalog: MALT1
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TBK1/IKKε-IN-4

TBK1-IKKε inhibitor II is a potent, selective dual inhibitor of TBK1/IKKε with IC50 of 13 nM/59 nM, respectively; displays 100- to 1000-fold less activity against other tested protein kinases including PDK1, PI3K family members and mTOR; inhibits LPS-induced expression of IFNβ (IC50=62 nM), and the IFNβ target genes IP10 (IC50=78 nM) and Mx1 (IC50=20 nM); effectively blocks TLR3-dependent IRF3 nuclear translocation in cells with IC50<100 nM.

  • CAS Number: 1381930-17-1
  • MF: C28H35N7O4
  • MW: 533.622
  • Catalog: IKK
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 668.1±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 357.9±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

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

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

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

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

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

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

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

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

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

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

AChE/Nrf2 modulator 1

AChE/Nrf2 modulator 1 is an orally active acetylcholinesterase (AChE)/nuclear factor erythroid 2-related factor 2 (Nrf2) modulator. AChE/Nrf2 modulator 1 has Nrf2 inductive activity and AChE inhibitory activity for eeAChE and hAChE with IC50 values of 0.07 μM and 0.38 μM, respectively. AChE/Nrf2 modulator 1 can be used for the research of Alzheimer's disease[1].

  • CAS Number: 2417117-84-9
  • MF: C27H27FN4O2
  • MW: 458.53
  • Catalog: AChE
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Isophysalin A

Isophysalin A is a physalin with alpha and beta unsaturated ketone components. Isophysalin A binds to GSH and targets multiple cysteine residues on IKKβ. Isophysalin A also inhibits inducible NO synthase (iNOS) and nitric oxide (NO) production, showing anti-inflammatory activity[1].

  • CAS Number: 1363398-67-7
  • MF: C28H30O10
  • MW: 526.53
  • Catalog: NO Synthase
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 846.6±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 286.6±27.8 °C

(S)-Falcarinol

(S)-Falcarinol (Panaxynol), one of the major polyacetylenes isolated from Panax ginseng, has antitumor activity. (S)-Falcarinol (Panaxynol) is the most potent antiplatelet agent in ginseng and its mechanism of action is chiefly due to the inhibition of thromboxane formation. (S)-Falcarinol (Panaxynol) is a potent Nrf2 activator[1][2][3].

  • CAS Number: 81203-57-8
  • MF: C17H24O
  • MW: 244.37200
  • Catalog: Keap1-Nrf2
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SN50

SN50 is a cell permeable inhibitor of NF-κB translocation. Sequence: Ala-Ala-Val-Ala-Leu-Leu-Pro-Ala-Val-Leu-Leu-Ala-Leu-Leu-Ala-Pro-Val-Gln-Arg-Lys-Arg-Gln-Lys-Leu-Met-Pro;AAVALLPAVLALLAPVQRKRQKLMP.

  • CAS Number: 213546-53-3
  • MF: C129H230N36O29S
  • MW: 2781.50000
  • Catalog: Peptides
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

IKK-IN-4

IKK-IN-4 is a potent and selective IkappaB kinase 2 (IKKβ orIKK2) inhibitor, with IC50s of 45 and 650 nM for IKKβ and IKKα, respectively[1].

  • CAS Number: 615529-94-7
  • MF: C18H19N5S
  • MW: 337.44
  • Catalog: IKK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Keap1-Nrf2 probe

Keap1-Nrf2 probe is a fluorescent Keap1-Nrf2 probe[1].

  • CAS Number: 2430031-36-8
  • MF: C48H72N10O19
  • MW: 1093.14
  • Catalog: Keap1-Nrf2
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BMS 345541

BMS-345541 free base 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: 445430-58-0
  • MF: C14H17N5
  • MW: 255.318
  • Catalog: IKK
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 449.5±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 225.6±28.7 °C

N-[(E)-(6-oxo-1-cyclohexa-2,4-dienylidene)methyl]-4-[3-[[[(E)-(6-oxo-1-cyclohexa-2,4-dienylidene)methyl]amino]carbamoyl]propylsulfanyl]butanehydrazide

Nrf2-IN-3 (Compound R16) is a Nrf2 inhibitor. Nrf2-IN-3 binds KEAP1 mutants (G333C mKEAP1) and repairs the disrupted KEAP1/NRF2 interactions. Nrf2-IN-3 sensitizes KEAP1-mutated cancer cells to Cisplatin (HY-17394) and Gefitinib (HY-50895) by repairing the mKEAP1/NRF2 complex[1].

  • CAS Number: 6325-13-9
  • MF: C22H26N4O4S
  • MW: 442.53
  • Catalog: Keap1-Nrf2
  • Density: 1.351g/cm3
  • Boiling Point: 621.9ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 329.9ºC

S-Allylmercaptocysteine

S-allylmercaptocysteine, an organic sulfur compound extracted from garlic, has anti-inflammatory and anti-oxidative effects for various pulmonary diseases. S-allylmercaptocysteine achieves its anti-cancer effect through a variety of pathways such as inducing the apoptosis of cancer cells through the TGF-β signaling pathway, or reducing the NF-κB activity and up-regulating Nrf2 to achieve the effects of anti-inflammation and anti-oxidation[1][2][3].

  • CAS Number: 2281-22-3
  • MF: C6H11NO2S2
  • MW: 193.29
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ACHP (Hydrochloride)

ACHP Hydrochloride is a highly potent and selective IKK-β inhibitor with an IC50 of 8.5 nM.

  • CAS Number: 406209-26-5
  • MF: C21H25ClN4O2
  • MW: 400.90200
  • Catalog: IKK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A