Olatec's Publications
​(click on title to link to publication)

Mechanism of Action
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OLT1177, a β-sulfonyl nitrile compound, safe in humans, inhibits the NLRP3 inflammasome and reverses the metabolic cost of inflammation. 
Marchetti, C., Swartzwelter, B., Gamboni, F., Neff, C. P., Richter, K., Azam, T., Carta, S., Tengesdal, I., Nemkov, T., D’Alessandro, A., Henry, C., Jones, G. S., Goodrich, S. A., St. Laurent, J. P., Jones, T. M., Scribner, C. L., Barrow, R. B., Altman, R. D., Skouras, D. B., Gattorno, M., Grau, V., Janciauskiene, S., Rubartelli, A., Joosten, L. A. B., Dinarello, C. A
Proceedings of the National Academy of Sciences
Jan 2018


Arthritis: Gout

Clinical
Dapansutrile, an oral selective NLRP3 inflammasome inhibitor, for treatment of gout flares: an open-label, dose-adaptive, proof-of-concept, phase 2a trial.
Klück, V., Jansen, T. L. T. A., Janssen, M., Comarniceanu, A., Efdé, M., Tengesdal, I. W., Schraa, K., Cleophas, M. C. P., Scribner, C. L., Skouras, D. B., Marchetti, C., Dinarello, C. A., Joosten, L. A. B. 
The Lancet Rheumatology
Apr 2020
 
Preclinical
NLRP3 inflammasome inhibitor OLT1177 suppresses joint inflammation in murine models of acute arthritis.
Marchetti, C., Swartzwelter, B., Koenders, M. I., Azam, T., Tengesdal, I. W., Powers, N., de Graaf, D. M., Dinarello, C. A., Joosten, L. A. B. 
Arthritis Research & Therapy
Aug 2018


Heart Failure

Clinical
A Phase IB, Randomized, Double-Blinded, Dose Escalation, Single Center, Repeat-Dose Safety and Pharmacodynamics Study of the Oral NLRP3 Inhibitor Dapansutrile in Subjects with NYHA II-III Systolic Heart Failure
Wohlford, G. F., Van Tassell, B. W., Billingsley, H.E, Kadariya, D., Canada, J. M., Carbone, S., Mihalick, V. L., Bonaventura, A., Vecchié, A., Chiabrando, J. G., Bressi, E., Thomas, G., Ho, A., Marawan, A. A., Dell, M., Trankle, C. R., Turlington, J., Markley, R., Abbate, A.
Journal of Cardiovascular Pharmacology
Jan 2021

Preclinical
The NLRP3 Inflammasome Inhibitor, OLT1177 (Dapansutrile), Reduces Infarct Size and Preserves Contractile Function After Ischemia Reperfusion Injury in the Mouse.
Toldo, S., Mauro, A. G., Cutter, Z., Tassell, B. W. V., Mezzaroma, E., Buono, M. G. D., Prestamburgo, A., Potere, N., Abbate, A. 
Journal of Cardiovascular Pharmacology
Apr 2019

Preservation of Contractile Reserve and Diastolic Function byInhibiting the NLRP3 Inflammasome with OLT1177® (Dapansutrile) in a Mouse Model of Severe Ischemic Cardiomyopathy Due to Non-Reperfused Anterior Wall Myocardial Infarction
Aliaga, J., Bonaventura, A., Mezzaroma, E., Dhakal, Y., Mauro, G., Abbate, A., Toldo, S.
Molecules
June 2021


Neuroinflammation

Preclinical
Multiple Sclerosis
OLT1177 (Dapansutrile), a Selective NLRP3 Inflammasome Inhibitor, Ameliorates Experimental Autoimmune Encephalomyelitis Pathogenesis.
Sánchez-Fernández, A., Skouras, D. B., Dinarello, C. A., & López-Vales, R.
Frontiers in Immunology
Nov 2019

Alzheimer's disease
The NLRP3 inflammasome inhibitor OLT1177 rescues cognitive impairment in a mouse model of Alzheimer’s disease
Lonnemann, N., Hosseini, S., Marchetti, C., Skouras, D.B., Stefanoni, D., D’Alessandro, A.,  Dinarello, C.A., Korte, M.
Proceedings of the National Academy of Sciences
Dec 2020

Cancer

Preclinical
Melanoma
Targeting tumor-derived NLRP3 reduces melanoma progression by limiting MDSCs expansion
Tengesdal, I. W., Menon, D. R., Osborne, D.G., Neff,  C. P., Powers,  N. E., Gamboni, F., Mauro, A. G., D’Alessandro, A., Stefanoni, D., Henen, M. A., Mills, T. S., De Graaf, D. M., Azam, T., Vogeli, B., Palmer, B. E.,  Pietras, E. M., DeGregori, J., Tan, A-C., Joosten, L. A. B., Fujita, M., Dinarello, C. A., Marchetti, C.
Proceedings of the National Academy of Sciences
Jan 2021

Tumor NLRP3-Derived IL-1β Drives the IL-6/STAT3 Axis Resulting in Sustained MDSC-Mediated Immunosuppression
Tengesdal, I. W., Dinarello, A., Powers, N. E., Burchill, M. A., Joosten, L. A. B., Marchetti, C., Dinarello, C. A.
Frontiers in Immunology
Aug 2021