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

Mechanism of Action
​
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
Nov 2020

Spinal Cord Injury
Inhibition of the NLRP3 inflammasome by OLT1177 induces functional protection and myelin preservation after spinal cord injury
Amo-Aparicio, J., Garcia-Garcia, J., Puigdomenech, M., Francos-Quijorna, I., Skouras, D. B., Dinarello, C. A., & Lopez-Vales, R. 
Experimental Neurology
Oct 2021

Parkinson's Disease
Pharmacologic inhibition of NLRP3 reduces the levels of α‐synuclein and protects dopaminergic neurons in a model of Parkinson’s disease
Amo‐Aparicio, J. , Daly, J., Falkesgaard Højen, J., & Dinarello, C. A.
Journal of Neuroinflammation
Jun 2023

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
Mar 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

Dexamethasone and OLT1177 Cooperate in the Reduction of Melanoma Growth by Inhibiting STAT3 Functions
Dinarello A, Mills TS, Tengesdal IW, Powers NE, Azam T, Dinarello CA
Cells
Jan 2023

Breast Cancer
Activation of Host-NLRP3 Inflammasome in Myeloid Cells Dictates Response to Anti-PD-1 Therapy in Metastatic Breast Cancers
Tengesdal, I. W., Li, S., Powers, N. E., May, M., Neff, C. P., Joosten, L., Marchetti, C., & Dinarello, C. A.
Pharmaceuticals (Basel, Switzerland)
May 2022

Pancreatic Cancer
Pancreatic Ductal Adenocarcinoma Cells Regulate NLRP3 Activation to Generate a Tolerogenic Microenvironment
Amo-Aparicio J, Dominguez A, Atif SM, Dinarello A, Azam T, Alula KM, Piper M, Lieu CH, Lentz RW, Leal AD, Bagby SM, Messersmith WA, Karam SD, Dinarello CA, Pitts TM, Marchetti C.
Cancer Research Communication
Sep 2023

Respiratory

Preclinical
Asthma
The NLRP3 Inflammasome Inhibitor, OLT1177 ® , Ameliorates Experimental Allergic Asthma in Mice
Lunding, L. P., Skouras, D. B., Vock, C., Dinarello, C. A., & Wegmann, M.
Allergy
Oct 2021


Fungal

Preclinical
Differential recognition and cytokine induction by the peptidorhamnomannan from Sporothrix brasiliensis and S. Schenckii
Kischkel, B., Lopes-Bezerra, L., Taborda, C. P., Joosten, L., Dos Santos, J. C., & Netea, M. G. 
Cellular Immunology​
June 2022