Adavivint
Adavivint Basic information
- Product Name:
- Adavivint
- Synonyms:
-
- N-(5-(3-(7-(3-fluorophenyl)-3H-imidazo[4,5-c]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-3-methylbutanamide
- CPD1633
- SM04690
- SM-04690;SM 04690;SM04690
- Butanamide, N-[5-[3-[7-(3-fluorophenyl)-3H-imidazo[4,5-c]pyridin-2-yl]-1H-indazol-5-yl]-3-pyridinyl]-3-methyl-
- Adavivint
- Wnt,SM 04690,Adavivint,SM04690,Lorecivivint,SM-04690,inhibit,Inhibitor
- Lorecivivint
- CAS:
- 1467093-03-3
- MF:
- C29H24FN7O
- MW:
- 505.55
- Mol File:
- 1467093-03-3.mol
Adavivint Chemical Properties
- Density
- 1.365±0.06 g/cm3(Predicted)
- storage temp.
- 2-8°C
- solubility
- DMSO:27.5(Max Conc. mg/mL);54.4(Max Conc. mM)
- pka
- 7.75±0.40(Predicted)
Adavivint Usage And Synthesis
Uses
Adavivint is an intra-articular potential disease-modifying osteoarthritis drug.
Biological Activity
Adavivint (SM04690) is a potent canonical Wnt signaling pathway inhibitor with EC50 of 19.5 nM for TCF/LEF reporter gene. It was more potent than other known Wnt inhibitors in multiple cellular experiments.
in vitro
Treatment of bone marrow-derived human mesenchymal stem cells (CD29+, CD44+ CD166+ CD105+ CD45-) with SM04690 induced a concentration-dependent decrease in Wnt pathway gene expression (ASCL1, LEF1, TCF7L2, TCF7 , C-262 MYC and AXIN2). Selective activation of Wnt signaling pathway with Wnt3a or GSK3β inhibitor CHIR-99021, in IEC6 (intestinal stem cells sensitive to Wnt activation), M04690 can inhibit the expression of AXIN2 and LGR5; in hMSCs, inhibit the expression of AXIN2, TCF7 and LEF1 Express. It has minimal effects on non-canonical Wnt signaling and BMP signaling. In vitro, SM04690 protects chondrocytes from metabolic breakdown.
in vivo
Intra-articular injection of Adavivint promotes cartilage growth and improves joint health in a rat model of knee osteoarthritis. In vivo, it reduces cartilage breakdown.