Adavivint (SM04690) - 97%, high purity , CAS No.1467093-03-3, Inhibitor of CDC like kinase 2;Inhibitor of dual specificity tyrosine phosphorylation regulated kinase 1A
Adavivint (SM04690) - 97%, high purity , CAS No.1467093-03-3, Inhibitor of CDC like kinase 2;Inhibitor of dual specificity tyrosine phosphorylation regulated kinase 1A
Adavivint (SM04690) is a potent and specific inhibitor of canonical Wnt signaling with an EC50 of 19.5 nM for inhibiting the TCF/LEF reporter. It is ∼150- to 500-fold more potent than the other known Wnt inhibitors across multiple cellular assays.
Storage Temp
Store at -20°C
Shipped In
Ice chest + Ice pads
Grade
Moligand™
Action Type
INHIBITOR
Mechanism of action
Inhibitor of CDC like kinase 2;Inhibitor of dual specificity tyrosine phosphorylation regulated kinase 1A
Product Description
Information
Adavivint (SM04690) Adavivint (SM04690) is a potent and specific inhibitor of canonical Wnt signaling with an EC50 of 19.5 nM for inhibiting the TCF/LEF reporter. It is ∼150- to 500-fold more potent than the other known Wnt inhibitors across multiple cellular assays.
Targets
Wnt
In vitro
Bone-marrow-derived hMSCs (CD29+, CD44+ CD166+ CD105+ CD45-), treated with SM04690, show a dose-dependent decrease in the expression of Wnt pathway genes (ASCL1, LEF1, TCF7L2, TCF7, C-262 MYC and AXIN2). M04690 also inhibits the expression of AXIN2, TCF7 and LEF1 in hMSCs and AXIN2 and LGR5 in IEC6 (intestinal stem cells sensitive to Wnt activation) when the Wnt pathway is selectively activated using either Wnt3a or a GSK3β inhibitor, CHIR-99021. SM04690 has minimal effects on the non-canonical Wnt pathway and the BMP pathway. SM04690 protects chondrocytes from catabolic breakdown in vitro.
In vivo
Intra-articular injection of SM04690 promotes cartilage growth and improves joint health in a rat model of knee osteoarthritis. It decreases cartilage breakdown in vivo.
1.Yates KE, Shortkroff S, Reish RG. (2005) Wnt influence on chondrocyte differentiation and cartilage function.. DNA Cell Biol, 24 (7):(446-57). [PMID:16008513]
2.Blom AB, Brockbank SM, van Lent PL, van Beuningen HM, Geurts J, Takahashi N, van der Kraan PM, van de Loo FA, Schreurs BW, Clements K et al.. (2009) Involvement of the Wnt signaling pathway in experimental and human osteoarthritis: prominent role of Wnt-induced signaling protein 1.. Arthritis Rheum, 60 (2):(501-12). [PMID:19180479]
3.Maeda A, Ono M, Holmbeck K, Li L, Kilts TM, Kram V, Noonan ML, Yoshioka Y, McNerny EM, Tantillo MA et al.. (2015) WNT1-induced Secreted Protein-1 (WISP1), a Novel Regulator of Bone Turnover and Wnt Signaling.. J Biol Chem, 290 (22):(14004-18). [PMID:25864198]
4.Yazici Y, McAlindon TE, Fleischmann R, Gibofsky A, Lane NE, Kivitz AJ, Skrepnik N, Armas E, Swearingen CJ, DiFrancesco A et al.. (2017) A novel Wnt pathway inhibitor, SM04690, for the treatment of moderate to severe osteoarthritis of the knee: results of a 24-week, randomized, controlled, phase 1 study.. Osteoarthr Cartil, 25 (10):(1598-1606). [PMID:28711582]
5.Deshmukh V, Hu H, Barroga C, Bossard C, Kc S, Dellamary L, Stewart J, Chiu K, Ibanez M, Pedraza M et al.. (2018) A small-molecule inhibitor of the Wnt pathway (SM04690) as a potential disease modifying agent for the treatment of osteoarthritis of the knee.. Osteoarthr Cartil, 26 (1):(18-27). [PMID:28888902]
6.Deshmukh V, O'Green AL, Bossard C, Seo T, Lamangan L, Ibanez M, Ghias A, Lai C, Do L, Cho S et al.. (2019) Modulation of the Wnt pathway through inhibition of CLK2 and DYRK1A by lorecivivint as a novel, potentially disease-modifying approach for knee osteoarthritis treatment.. Osteoarthr Cartil, 27 (9):(1347-1360). [PMID:31132406]
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D2315492