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Product Data Sheet Product data sheet MedKoo Cat#: 319577 Name: Dapansutrile CAS#: 54863-37-5 Chemical Formula: C4H7NO2S Exact Mass: 133.0197 Molecular Weight: 133.17 Product supplied as: Powder Purity (by HPLC): ≥ 98% Shipping conditions Ambient temperature Storage conditions: Powder: -20°C 3 years; 4°C 2 years. In solvent: -80°C 3 months; -20°C 2 weeks. 1. Product description: Dapansutrile, also known as OLT1177, is an anti-inflammatory, analgesic drug candidate. Dapansutrile is a β-sulfonyl nitrile inhibitor of the NLRP3 inflammasome that inhibits the release of IL-1β and decreases caspase-1 levels in LPS-stimulated J774A. murine macrophages, human monocyte derived macrophages (HMDMs), and primary human blood neutrophils without affecting TNF-α release. 2. CoA, QC data, SDS, and handling instruction SDS and handling instruction, CoA with copies of QC data (NMR, HPLC and MS analytical spectra) can be downloaded from the product web page under “QC And Documents” section. Note: copies of analytical spectra may not be available if the product is being supplied by MedKoo partners. Whether the product was made by MedKoo or provided by its partners, the quality is 100% guaranteed. 3. Solubility data Solvent Max Conc. mg/mL Max Conc. mM DMSO 60.0 450.55 H2O 68.0 510.63 4. Stock solution preparation table: Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg 1 mM 7.51 mL 37.55 mL 75.09 mL 5 mM 1.50 mL 7.51 mL 15.02 mL 10 mM 0.75 mL 3.75 mL 7.51 mL 50 mM 0.15 mL 0.75 mL 1.50 mL 5. Molarity Calculator, Reconstitution Calculator, Dilution Calculator Please refer the product web page under section of “Calculator” 6. Recommended literature which reported protocols for in vitro and in vivo study In vitro study 1. Tengesdal IW, Menon DR, Osborne DG, Neff CP, Powers NE, Gamboni F, Mauro AG, D'Alessandro A, Stefanoni D, Henen MA, Mills TS, De Graaf DM, Azam T, Vogeli B, Palmer BE, Pietras EM, DeGregori J, Tan AC, Joosten LAB, Fujita M, Dinarello CA, Marchetti C. Targeting tumor-derived NLRP3 reduces melanoma progression by limiting MDSCs expansion. Proc Natl Acad Sci U S A. 2021 Mar 9;118(10):e2000915118. doi: 10.1073/pnas.2000915118. PMID: 33649199; PMCID: PMC7958415. In vivo study 1. Marchetti C, Swartzwelter B, Koenders MI, Azam T, Tengesdal IW, Powers N, de Graaf DM, Dinarello CA, Joosten LAB. NLRP3 inflammasome inhibitor OLT1177 suppresses joint inflammation in murine models of acute arthritis. Arthritis Res Ther. 2018 Aug 3;20(1):169. doi: 10.1186/s13075-018-1664-2. PMID: 30075804; PMCID: PMC6091035. 2. Sánchez-Fernández A, Skouras DB, Dinarello CA, López-Vales R. OLT1177 (Dapansutrile), a Selective NLRP3 Inflammasome Inhibitor, Ameliorates Experimental Autoimmune Encephalomyelitis Pathogenesis. Front Immunol. 2019 Nov 1;10:2578. doi: 10.3389/fimmu.2019.02578. PMID: 31736980; PMCID: PMC6839275. MedKoo Biosciences || http://www.medkoo.com || [email protected] 2500 Gateway Centre Blvd Suite 400, Morrisville, NC27560, USA. Tel: 919-636-5577, Fax: 919-980-4831 Product data sheet 7. Bioactivity Biological target: Dapansutrile is a potent, selective and orally active inhibitor of NLRP3 inflammasome. Anti-inflammatory, analgesic activity. In vitro activity NLRP3 with OLT1177, a small synthetic, orally active specific NLRP3 inhibitor (KD = 1.2 µM) (SI Appendix, Fig. S2B) was next targeted. OLT1177 blocks the ATPase activity of NLRP3, a function required for the formation of the NLRP3 inflammasome. Treatment with OLT1177 reduced both spontaneous and IL-1α–induced secretion of IL-1β in 1205Lu cells (−73% and −87%, respectively) (Fig. 1 G and H). Expectedly, in 1205Lu cells, treatment with OLT1177 had no effect on NLRP3, ASC, and the IL-1β precursor (p37) protein levels when compared to the vehicle-treated cultures (Fig. 1I). No effect of OLT1177 on proliferation was measured in 1205Lu, A375, and HS294T (SI Appendix, Fig. S2G). These in vitro findings demonstrate constitutive NLRP3 inflammasome activation in human melanoma cells and its role in the processing and secretion of IL-1β. Reference: Proc Natl Acad Sci U S A. 2021 Mar 9; 118(10): e2000915118. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958415/ In vivo activity In the current study, the therapeutic effect of OLT1177, an orally active NLRP3 inflammasome inhibitor that is safe in humans, was assessed in murine acute arthritis models. OLT1177 reduced zymosan-induced joint swelling (p < 0.001), cell influx (p < 0.01), and synovial levels of interleukin (IL)-1β, IL-6, and chemokine (C-X-C motif) ligand 1 (CXCL1) (p < 0.05), respectively, when compared with vehicle-treated mice. Plasma OLT1177 levels correlated (p < 0.001) dose-dependently with reduction in joint inflammation. Treatment of mice with OLT1177 limited MSU crystal articular inflammation (p > 0.0001), which was associated with decreased synovial IL-1β, IL-6, myeloperoxidase, and CXCL1 levels (p < 0.01) compared with vehicle-treated mice. When administrated orally 1 hour after MSU challenge, OLT1177 reduced joint inflammation, processing of IL-1β, and synovial phosphorylated c-Jun N- terminal kinase compared with the vehicle group. Mice were fed an OLT1177-enriched diet for 3 weeks and then challenged i.a. with MSU crystals. Joint swelling, synovial IL-1β, and expression of Nlrp3 and Il1b were significantly reduced in synovial tissues in mice fed an OLT1177-enriched diet when compared with the standard diet group. Reference: Arthritis Res Ther. 2018 Aug 3;20(1):169. https://pubmed.ncbi.nlm.nih.gov/30075804/ Note: The information listed here was extracted from literature. MedKoo has not independently retested and confirmed the accuracy of these methods. Customer should use it just for a reference only. MedKoo Biosciences || http://www.medkoo.com || [email protected] 2500 Gateway Centre Blvd Suite 400, Morrisville, NC27560, USA. Tel: 919-636-5577, Fax: 919-980-4831 .
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