Adavivint

• CAS: 1467093-03-3
• Catalog Number: ACM1467093033
• Category: Inhibitors
• Molecular Weight: 505.56
• Molecular Formula: C29H24FN7O
• Description: Adavivint, also known as SM04690 and LORECIVIVINT, is a small-molecule inhibitor of the Wnt pathway which is being investigated as a potential disease modifying agent for the treatment of osteoarthritis of the knee
• Synonyms: Adavivint; SM-04690; SM04690; SM 04690
• IUPAC Name: N-(5-(3-(7-(3-Fluorophenyl)-3H-imidazo(4,5-C)pyridin-2-yl)-1H-indazol-5- yl)-pyridin-3-yl)-3-methylbutanamide
• Canonical SMILES: CC(C)CC(=O)Nc1cncc(c1)c2ccc3[nH]nc(c4nc5c(cncc5[nH]4)c6cccc(F)c6)c3c2
• InChI: 1S/C29H24FN7O/c1-16(2)8-26(38)33-21-10-19(12-31-13-21)17-6-7-24-22(11-17)28(37-36-24)29-34-25-15-32-14-23(27(25)35-29)18-4-3-5-20(30)9-18/h3-7,9-16H,8H2,1-2H3,(H,33,38)(H,34,35)(H,36,37)
• InChI Key: AQDWDWAYVBQMAM-UHFFFAOYSA-N
• Solubility: Soluble in DMSO
• Appearance: Solid powder
• Shelf Life: >3 years if stored properly
• Storage: Dry, dark and at 0-4 °C for short term (days to weeks) or -20 °C for long term (months to years).
• Biological Target: Adavivint (SM04690; Lorecivivint) is an inhibitor of canonical Wnt signaling, with an EC50 of 19.5 nM via a high-throughput TCF/LEF-reporter assay in SW480 colon cancer cells.
• Drug Formulation: This drug may be formulated in DMSO
• Elemental Analysis: C, 68.90; H, 4.79; F, 3.76; N, 19.39; O, 3.16
• Exact Mass: 505.2026
• HS Tariff Code: 2934.99.9001
• In Vitro Activity: SM04690 induced a robust apoptotic response in HEC108 cells (Ctrl, 0.65% vs. 128 nmol/L 28.5% Annexin V/PI positive). With respect to proliferation, SM04690 significantly inhibited BrdU incorporation and an exceptional inhibition in the HEC265 cell lines. These data highlight that the CTNNB1-mutant cells lines are more sensitive to SM04690. The source of this sensitivity does seem to vary among cell lines, with HEC108 demonstrating a proapoptotic response and HEC265 demonstrating an antiproliferative response, likely due to each cell line's larger mutational profile.; Reference: Mol Carcinog. 2021 May 26. doi: 10.1002/mc.23308. https://pubmed.ncbi.nlm.nih.gov/34038589/
• In Vivo Activity: The efficacy of a single intradiscal injection of LOR (Adavivint) (0.33 µg) or vehicle was evaluated in the needle-puncture model of DDD (degenerative disc disease). Radiographic measurement of disc heights showed a DHI of 0.12±0.01 prior to injury. One week after needle-puncture surgery and prior to treatment of the NP of injured discs, DHI was reduced to 0.095±0.01 (~80% of baseline). Five weeks after dosing (6 weeks post injury), disc height was further reduced (DHI=0.083±0.01; ~68% of baseline and ~87% of Week 1) in vehicle-treated rats. Five weeks after dosing, disc height (ie, DHI) was maintained (DHI=0.096±0.01; ~80% of baseline and ~101.6% of Week 1) in LOR-treated rats and was significantly (p=.012) higher than that in vehicle-treated rats. When disc height was measured using quantitative histomorphometric analysis, LOR-treated rats demonstrated greater disc heights (789.6±15.8 µm) than vehicle-treated rats (692.7±11.6 µm).; Reference: Osteoarthritis Cartilage. 2018 Jan;26(1):18-27. https://pubmed.ncbi.nlm.nih.gov/32413487/
• Shipping: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
• Stock Solution Storage: 0-4 °C for short term (days to weeks), or -20 °C for long term (months).