It is associated with the NLRP3 gene (also is known as CIAS1) which encodes cryopyrin
. This protein is part of the NALP3 inflammasome cascade.
Newton et al., "Cryopyrin
activates the inflammasome in response to toxins and ATP," Nature, vol.
Bergstralh et al., "NLRP3 (NALP3, Cryopyrin
) facilitates in vivo caspase-1 activation, necrosis, and HMGB1 release via inflammasome-dependent and -independent pathways," The Journal of Immunology, vol.
(b) positive results in Phase 2 or 3 trial, (c) proof of concept obtained, (d) no positive results in Phase 2 or 3, RA: rheumatoid arthritis, JIA: juvenile idiopathic arthritis, CD: Crohn's disease, UC: ulcerative colitis, AS: ankylosing spondylitis, SpA: spondyloathritis, PS: psoriasis, PsA: psoriatic arthritis, CAPS: cryopyrin
associated periodic syndrome, FMF: familial medetrian fever, SLE: systemic lupus erythematosus, pSS: primary Sjogren's syndrome, SSc: systemic sclerosis, CCA: giant cell arthritis, TA: Takayasu arteritis, AAV: ANCA associated vasculitis, AOSD: adult-onset Still's disease
The diseases described in this scope include FMF, tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS), mevalonate kinase deficiency/hyperimmunoglobulin D syndrome (MKD-HIDS), NLRP12- related syndrome (NLRP12AD), Blau syndrome, pyogenic arthritis, pyoderma gangrenosum and acne syndrome (PAPAs), early-onset sarcoidosis (EOS), Majeed syndrome (MS), interleukin-1 receptor antagonist deficiency (DIRA), cryopyrin
associated periodic syndromes (CAPS), IL-36 receptor antagonist deficiency (DITRA), CARD14-mediated pustular psoriasis (CAMPS) and chronic atypical neutrophilic dermatosis, lypodistrophy, and elevated temperature (CANDLE).
Zhang et al., "Cryopyrin
and pyrin activate caspase-1, but not NF-[kappa][beta], via ASC oligomerization," Cell Death and Differentiation, vol.
The revised agreement builds on the previous agreement that gave Sobi rights for Kineret within the field of Rheumatoid arthritis (RA) and four orphan drug indications, including Cryopyrin
Associated Periodic Syndrome (CAPS).
, the protein encoded by NLRP3, controls the inflammasome, a crucial molecular platform that regulates activation of caspase-1 and processing of interleukin (IL)-1[beta], two key mediators of inflammation (Martinon and Tschopp, 2006; Mariathasan and Monack, 2007; Petrilli et al., 2007).
There have been seven established NLRs that form an inflammasome complex: NLRP1 (NALP1), NLRP3 (NALP3 or cryopyrin
), NLRP6, NLRP12, NLRC4 (with caspase recruitment domain or IPAF), AIM2 (absent in melanoma-2), and RIG-1 (retinoic acid inducible gene-1); however, the NLRP3 inflammasome is the best characterized in relation with renal diseases .
The abstract summarizing the data is titled "NOMID-Associated Complications in Mice Are Prevented By CDD-450, a Small Molecule Inhibitor of the Mitogen-Activated Protein Kinase-Activated Protein Kinase 2, or MK2, Pathway." In pre-clinical studies, ATI-450 was active in blocking multiple manifestations of the Neonatal-onset Multisystem Inflammatory Disease, or NOMID, form of Cryopyrin
associated periodic syndromes, or CAPS, using an inducible transgenic murine model of the disease.