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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Luteolin

Luteolin is a falconoid compound, which exhibits anticancer properties.IC50 value:Target: A natural for anticancer.In vitro: Luteolin exerted an anticancer effect against NCI-H460 cells through Sirt1-mediated apoptosis and the inhibition of cell migration [1]. The treatment of luteolin upregulated the expression levels of transforming growth factor β1 (TGF-β1), p21WAF1/CIP1, p27KIP1, Smad4, and Fas in HCC cells. Luteolin induced apoptotic cell death in Hep3B cells while caused G1 arrest in HepG2 cells. And it induces apoptosis from G1 arrest via three signaling pathways of TGF-β1, p53, and Fas/Fas-ligand in HCC cells [2].In vivo: The study of the effect of Luteolin on the improvement of cancerous cachexia in model mice showed that luteolin can improve the symptoms of cancer cachexia model mice.The mechanism may be related to inhibition of proteasome and calcium activated protease activity and lower the levels of cytokines [3].

  • CAS Number: 491-70-3
  • MF: C15H10O6
  • MW: 286.236
  • Catalog: Apoptosis
  • Density: 1.7±0.1 g/cm3
  • Boiling Point: 616.1±55.0 °C at 760 mmHg
  • Melting Point: ~330 °C(lit.)
  • Flash Point: 239.5±25.0 °C

MALT1-IN-6

MALT1-IN-6 is a potent MALT1 protease inhibitor with a Ki of 9 nM. MALT1-IN-6 has anticancer effects (WO2018226150A1; Compound 4)[1].

  • CAS Number: 2254669-07-1
  • MF: C18H12Cl2F3N9O
  • MW: 498.25
  • Catalog: MALT1
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Nrf2 activator-4

Nrf2 activator-4 (Compound 20a) is a highly potent, orally active Nrf2 activator with an EC50 of 0.63 µM. Nrf2 activator-4 suppresses reactive oxygen species against oxidative stress in microglia. Nrf2 activator-4 effectively recovers the learning and memory impairment in a scopolamine-induced mouse model[1].

  • CAS Number: 2383016-68-8
  • MF: C23H24ClF3N2O3
  • MW: 468.90
  • Catalog: Keap1-Nrf2
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(R)-MLT-985

(R)-MLT-985 (compound 11) is a potent MALT1 protease inhibitor with an IC50 of 3 nM. (R)-MLT-985 has an IC50 of 20 nM for MALT1-dependent IL-2 production in Jurkat cells. (R)-MLT-985 suppresses growth and aberrant CARD11/BCL10/MALT1 complex signaling in ABC-DLBCL cells[1].

  • CAS Number: 1832577-07-7
  • MF: C17H15Cl2N9O2
  • MW: 448.27
  • Catalog: MALT1
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cga-jk3

CGA-JK3 is an IkappaB kinase inhibitor in innate immune process.

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

ML 334

ML334 is a potent, cell permeable activator of NRF2 by inhibition of Keap1-NRF2 protein-protein interaction. ML334 binds to Keap1 Kelch domain with a Kd of 1 μM. ML334 stimulates NRF2 expression and nuclear translocation and induces antioxidant response elements (ARE) activity[1][2].

  • CAS Number: 1432500-66-7
  • MF: C26H26N2O5
  • MW: 446.50
  • Catalog: Keap1-Nrf2
  • Density: 1.354±0.06 g/cm3(Predicted)
  • Boiling Point: 693.1±55.0 °C(Predicted)
  • Melting Point: N/A
  • Flash Point: N/A

Plantainoside D

Plantainoside D shows ACE inhibitory activity with IC50 2.17 mM[1]. And plantainoside D is a promising IKK-β inhibitor[2].

  • CAS Number: 147331-98-4
  • MF: C29H36O16
  • MW: 640.59
  • Catalog: Angiotensin-converting Enzyme (ACE)
  • 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

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

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

Mangiferin

Mangiferin is a Nrf2 activator. Mangiferin suppresses nuclear translocation of the NF-κB subunits p65 and p50.

  • CAS Number: 4773-96-0
  • MF: C19H18O11
  • MW: 422.340
  • Catalog: Keap1-Nrf2
  • Density: 1.8±0.1 g/cm3
  • Boiling Point: 842.7±65.0 °C at 760 mmHg
  • Melting Point: 269-270ºC
  • Flash Point: 303.6±27.8 °C

SC-514

SC-514 is a selective IKK-2 inhibitor (IC50=11.2±4.7 μM), which does not inhibit other IKK isoforms or other serine-threonine and tyrosine kinases.

  • CAS Number: 354812-17-2
  • MF: C9H8N2OS2
  • MW: 224.303
  • Catalog: IKK
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 399.2±42.0 °C at 760 mmHg
  • Melting Point: 209-211°C
  • Flash Point: 195.2±27.9 °C

MLT-747

MLT-748 is a allosteric inhibitor of MALT1, binds MALT1 in the allosteric Trp580 pocket, with an IC50 of 5 nM. MLT-748 also reversibly binds to human mutant MALT1(329-728)-W580S (Kd, 13 nM) with affinity similar to that of the wild type MALT1(329-728) (Kd, 42 nM)[1].

  • CAS Number: 2097853-86-4
  • MF: C20H21Cl2N7O3
  • MW: 478.33
  • Catalog: MALT1
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MALT1-IN-5

MALT1-IN-5 (compound 1) is a potent MALT1 protease inhibitor. MALT1-IN-5 can be used for cancer research[1].

  • CAS Number: 2434602-73-8
  • MF: C17H17ClF2N6O3
  • MW: 426.81
  • Catalog: MALT1
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Oxaprozin, potassium salt

Oxaprozin potassium is an orally active and potent COX inhibitor, with IC50 values of 2.2 μM for human platelet COX-1 and and 36 μM for IL-1-stimulated human synovial cell COX-2, respectively. Oxaprozin potassium also inhibits the activation of NF-κB. Oxaprozin potassium induces cell apoptosis. Oxaprozin potassium shows anti-inflammatory activity. Oxaprozin potassium-mediated inhibition of the Akt/IKK/NF-κB pathway contributes to its anti-inflammatory properties[1][2].

  • CAS Number: 174064-08-5
  • MF: C18H14KNO3
  • MW: 331.40700
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: 467ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 236.2ºC

TML-6-d3

TML-6-d3 is the deuterium labeled TML-6. TML-6, an orally active curcumin derivative, inhibits the synthesis of the β-amyloid precursor protein and β-amyloid (Aβ). TML-6 can upregulate Apo E, suppress NF-κB and mTOR, and increase the activity of the anti-

  • CAS Number: 2673270-28-3
  • MF: C30H34D3NO7
  • MW: 526.64
  • Catalog: Keap1-Nrf2
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Keap1-Nrf2-IN-5

Keap1-Nrf2-IN-5 (compound 1) is a potent Keap1-Nrf2 PPI (Keap1-Nrf2 protein−protein interaction) inhibitor with an IC50 of 4.1 µM, Kd of 3.7 µM[1].

  • CAS Number: 2696272-70-3
  • MF: C23H30N4O6S
  • MW: 490.57
  • Catalog: Keap1-Nrf2
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Resveratrol analog 2

Resveratrol analog 2 is an analog of Resveratrol (HY-16561). Resveratrol is a natural polyphenolic phytoalexin that possesses anti-oxidant, anti-inflammatory, cardioprotective, and anti-cancer properties[1].

  • CAS Number: 915378-82-4
  • MF: C16H13FO3
  • MW: 272.27
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ezetimibe Ketone

Ezetimibe ketone (EZM-K) is a phase-I metabolite of Ezetimibe. Ezetimibe is a Niemann-Pick C1-like1 (NPC1L1) inhibitor, and is a potent Nrf2 activator. Ezetimibe is a potent cholesterol absorption inhibitor[1][2][3].

  • CAS Number: 191330-56-0
  • MF: C24H19F2NO3
  • MW: 407.409
  • Catalog: Autophagy
  • Density: 1.325
  • Boiling Point: 656.1±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 350.6±31.5 °C

Eriodictyol-7-O-glucoside

Eriodictyol-7-O-glucoside (Eriodictyol 7-O-β-D-glucoside), a flavonoid, is a potent free radical scavenger. Eriodictyol-7-O-glucoside is also an Nrf2 activator, confers protection against Cisplatin-induced toxicity[1].

  • CAS Number: 38965-51-4
  • MF: C21H22O11
  • MW: 450.393
  • Catalog: Keap1-Nrf2
  • Density: 1.7±0.1 g/cm3
  • Boiling Point: 841.0±65.0 °C at 760 mmHg
  • Melting Point: 171-176ºC
  • Flash Point: 296.9±27.8 °C

BAY 11-7082

BAY 11-7082 is a NF-κB inhibitor which decreases NF-κB by inhibiting TNF-α-induced phosphorylation of IκB-α. BAY 11-7082 inhibits ubiquitin-specific protease USP7 and USP21 with IC50s of 0.19 μM and 0.96 μM, respectively.

  • CAS Number: 19542-67-7
  • MF: C10H9NO2S
  • MW: 207.249
  • Catalog: Autophagy
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 397.6±42.0 °C at 760 mmHg
  • Melting Point: 133-135℃
  • Flash Point: 194.3±27.9 °C

MALT1-IN-8

MALT1-IN-8 is a potent MALT1 protease inhibitor with a IC50 of 2 nM. MALT1-IN-8 inhibits the growth of OCI-LY3 lymphoma cells with an IC50 of 1.16 μM. MALT1-IN-8 has anticancer effects (WO2018165385A1; Compound 8)[1].

  • CAS Number: 2244109-29-1
  • MF: C20H15Cl2N7O
  • MW: 440.29
  • Catalog: MALT1
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MALT1-IN-11

MALT1-IN-11 (Example 151 in reference Patent) is a MALT1 protease inhibitor (IC50 < 10 nM). MALT1-IN-11 inhibits IL10 secretion with an IC50 of 10-100 nM. MALT1-IN-11 can be used for the research of cancer, autoimmune and inflammatory disorders[1].

  • CAS Number: 2812352-99-9
  • MF: C20H16F4N8O
  • MW: 460.39
  • Catalog: MALT1
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Gingerenone A

Gingerenone A is a Nrf2-Gpx4 activator with anti-breast-cancer properties. Gingerenone A results a delayed G2/M in cancer cells, following oxidative stress and senescence responses. Gingerenone A also alleviates ferroptosis in secondary liver injury (SLI) in dextran sodium sulfate (DSS)-induced colitis mice. Gingerenone A can be isolated from Zingiber officinale[1][2].

  • CAS Number: 128700-97-0
  • MF: C21H24O5
  • MW: 356.41
  • Catalog: Keap1-Nrf2
  • Density: 1.183g/cm3
  • Boiling Point: 571.3ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 200.3ºC

TBK1/IKKε-IN-1(compound 1)

TBK1/IKKε-IN-5 (compound 1) is a dual TBK1 and IKKε inhibitor, with IC50 values of 1 nM and 5.6 nM for TBK1 and IKKε, respectively[1].

  • CAS Number: 1893397-65-3
  • MF: C28H31N7O3
  • MW: 513.59
  • Catalog: IKK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(+)-Corynoline

Corynoline, isolated from Corydalis incise (Papaveraceae), is a reversible and noncompetitive acetylcholinesterase (AChE) inhibitor with an IC50 of 30.6 μM[1]. Corynoline exhibits anti-inflammatory activity by activating Nrf2[2].

  • CAS Number: 18797-79-0
  • MF: C21H21NO5
  • MW: 367.395
  • Catalog: AChE
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 504.2±50.0 °C at 760 mmHg
  • Melting Point: 217-218ºC
  • Flash Point: 258.7±30.1 °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

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

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