MCC950

NLRP3 Inflammasome Inhibitor



MCC950 is a potent, selective and orally available inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases.

MCC950 is a highly potent specific NLRP3 inhibitor with demonstrated in vivo activity in multiple NLRP3-dependent mouse models1 and in ex vivo samples from individuals with Cryopyrin-Associated Periodic Syndrome (CAPS). MCC950 is thus a potential therapeutic for NLRP3-associated syndromes, including auto-inflammatory and auto-immune diseases, and a valuable tool for study of the role of NLRP3 inflammasome activation in human health and disease.

MCC950, previously known as CRID3 is now available for immediate dispatch from Avistron Chemistry Services in a number of pack sizes, please contact Avistron to place your order.

  1. J Pharmacol Exp Ther. 2001 Oct;299(1):187-97.
    Identification and characterization of a novel class of interleukin-1 post-translational processing inhibitors.


MCC950 Properties

  • Potent & Specific NLRP3 inhibitor- IC50 7 nM in human or mouse macrophages.
  • Specific Inhibition of IL-1β secretion , LPS-dependent TNF-α secretion unimpaired.
  • • No inhibition of NLRC4, AIM2, NLRP3 priming or Toll-like receptor signaling
  • Oral bioavailability = 68% & Half-Life = 3.27hr (mouse)
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mcc950 Inflammasome Inhibitor


The NOD-like receptor (NLR) family, pyrin domain–containing protein 3 (NLRP3) inflammasome is a component of the inflammatory process, and its aberrant activation is pathogenic in inherited disorders such as cryopyrin-associated periodic syndrome (CAPS) and complex diseases such as multiple sclerosis, type 2 diabetes, Alzheimer’s disease and atherosclerosis. MCC950 blocks canonical and noncanonical NLRP3 activation at nanomolar concentrations, MCC950 also specifically inhibits activation of NLRP3 but not the AIM2, NLRC4 or NLRP1 inflammasome. Further MCC950 reduces interleukin-1b (IL-1b) production in vivo and attenuates experimental autoimmune encephalomyelitis (EAE), a disease model of multiple sclerosis. MCC950 has displayed effective treatment in a mouse model of CAPS and was active in ex vivo samples from individuals with Muckle–Wells syndrome.1

The NLR family protein NLRP3 is an intracellular signaling molecule that senses many pathogen-derived, environmental and host-derived factors2. Upon activation, NLRP3 binds to apoptosis-associated speck-like protein containing a CARD (ASC). ASC in turn interacts with the cysteine protease caspase-1 to form a complex termed the inflam¬masome. This results in the activation of caspase-1, which cleaves the proinflammatory cytokines IL-1β and IL-18 to their active forms and mediates a type of inflammatory cell death known as pyroptosis.3 Other intracellular pattern recognition receptors (PRRs) are also capable of forming inflammasomes. These include other NLR family members such as NLRP1 and NLRC4, as well as non-NLR PRRs such as the double-stranded DNA (dsDNA) sensors absent in melanoma 2 (AIM2) and interferon, gamma inducible protein 16 (IFI16).4 NLRP3-dependent IL-1β processing can also be activated by an indirect, non-canonical pathway downstream of caspase-11.5

  1. 1 Coll, R.C., Robertson, A.A.B., Chae, J.J., Higgins, S.C., Muñoz-Planillo, R., Inserra, M.C., Vetter, I., Dungan, L.S., Monks, B.G., Stutz, A., Croker, D.E., Butler, M.S., Haneklaus, M., Sutton, C.E., Núñez, G., Latz, E., Kastner, D.L., Mills, K.H.G., Masters, S.L., Schroder, K., Cooper, M.A., O’Neill, L.A.J. A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases. Nature Medicine, 21,248–255 (2015).
  2. Wen, H., Miao, E.A. & Ting, J.P. Mechanisms of NOD-like receptor-associated inflammasome activation. Immunity 39, 432–441 (2013).
  3. Schroder, K. & Tschopp, J. The inflammasomes. Cell 140, 821–832 (2010).
  4. Latz, E., Xiao, T.S. & Stutz, A. Activation and regulation of the inflammasomes. Nat. Rev. Immunol. 13, 397–411 (2013).
  5. Lamkanfi, M. & Dixit, V.M. Mechanisms and functions of inflammasomes. Cell 157, 1013–1022 (2014).

Keywords:
MCC950; NLRP3; NLRP3 inhibitor; NLRP3-dependent mouse model; cryopyrin-associated periodic syndrome; CAPS; NLRP3-associated syndromes; autoinflammatory; autoimmune diseases; NLRP3 inflammasome; apoptosis-associated speck-like protein; CARD; ASC; cysteine protease; caspase-1; inflam¬masome; proinflammatory cytokines; IL-1β; IL-18; pyroptosis; pattern recognition receptors (PRRs); NLRP1; NLRC4; non-NLR PRRs; melanoma 2; AIM2; interferon; gamma inducible protein 16; IFI16; NLRP3-dependent; IL-1β processing; caspase-11; NOD-like receptor; NLR family; pyrin domain–containing protein 3 (NLRP3) inflammasome; inflammatory process; multiple sclerosis; type 2 diabetes; Alzheimer’s disease; atherosclerosis; experimental autoimmune encephalomyelitis; EAE; multiple sclerosis; Muckle–Wells syndrome.

Custom Synthesis

Avistron offers you custom synthesis of key compounds, scaffolds and building blocks on a variety of scales at very reasonable rates depending on your specific needs. Our compound collection includes a variety of structural types and is constantly growing to meet the demands of the industry.

Avistron is also a supplier of novel tools for laboratory research, for instance compounds such as the potent and specific glycogen synthase kinase-3 (GSK3) inhibitors CHIR99021 (AV02506) and SB627772 (AV00300) are amongst the compounds offered by Avistron.

We ensure that our products are always of high quality and purity so that you can be confident that you are giving your projects the very best chance of success.

Please contact us to discuss your specific requirements

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MCC950 Avistron offers you custom synthesis of key compounds, scaffolds and building blocks

Computational Chemistry Services

We have access to state of the art design software tools which in the hands of our computational chemistry experts mean that we can design and deliver the compounds which are most likely to be those that you need to accelerate your drug discovery programmes.

We have key capabilities in the following areas:

  • Ligand and structure-based design
  • Wide-ranging domain expertise
  • Hit identification and optimisation driven by activity, selectivity and ADME properties
  • Library design and data mining
  • Template hopping to navigate IP space and to identify ideas with potential for development
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MCC950 Avistron - Computational Chemistry Services

Project management for your drug discovery projects

Our dedicated and professional team of project managers has extensive medicinal chemistry experience in the pharmaceutical and contract research sectors and as such we are able to rapidly understand your requirements and make an impact in the acceleration of your drug discovery programmes.

We have significant experience of managing all aspects of drug discovery collaborations, from computational chemistry, to synthesis, to ADME, to screening and across a broad range of therapeutic areas.

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MCC950 Avistron offers you custom synthesis of key compounds, scaffolds and building blocks

Contact

If you would like to order MCC950 or just require more information on this or our other products and services, please use the form below. We would be pleased to receive your orders and enquiries at our UK headquarters by email, phone, fax or post.

Avistron Chemistry Services Ltd

38 Lansdown Road, Bude
Cornwall, United Kingdom

P: +44 (0)7896 979 531

P: +44 (0)5603 152 978

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