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Chemical Structure : SK-124
CAS No.: 2760404-50-8
Catalog No.: PC-49563Not For Human Use, Lab Use Only.
SK-124 (SK124) is a potent, selective, orally active SIK2/SIK3 inhibitor with IC50 of 8.8/11.3 nM in cell-based NanoBRET assays, 15-fold selectivity versus SIK1.
| Packing | Price | Stock | Quantity |
|---|---|---|---|
| 2 mg | $228 | In stock | |
| 5 mg | $368 | In stock | |
| 10 mg | $568 | In stock | |
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| 100 mg | Get quote |
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SK-124 (SK124) is a potent, selective, orally active SIK2/SIK3 inhibitor with IC50 of 8.8/11.3 nM in cell-based NanoBRET assays, 15-fold selectivity versus SIK1.
SK-124 potently inhibits SIK2/SIK3 with IC50 of 0.41/1.2 nM in radioisotope kinase assays, respectively.
SK-124 displays acceptable oral bioavailability in mice, robust stability in human, rat, and mouse liver microsomes, no inhibition of cytochrome P450 enzymes.
SK-124 exhibits no significant off-target activities at 10 µM in the Eurofins SafetyScreen44 panel, PDGFRα (IC50=15.8 nM) is the major off-target kinase.
SK-124 engages endogenous SIK2 in murine osteocyte-like Ocy454 cells, reduces phosphorylation of SIK substrates HDAC4/HDAC5 and CRTC2 in murine Ocy454 and human Saos2 cells, promotes CRTC2 (EC50=128 nM in ) and HDAC5 nuclear translocation, and regulated SIK target gene [SOST and TNFSF11 (also known as RANKL)] expression in a PTH-like manner without causing cytotoxicity.
Oral SK-124 (40 mg/kg) treatment increased P1NP and C terminal telopeptide (CTX) compared with oral vehicle solution in a manner similar to that of once-daily subcutaneous PTH treatmentparathyroid hormone (PTH).
3 wk of 40 mg/kg SK-124 treatment led to changes consistent with intermittent PTH therapy and inducible SIK2/SIK3 deletion including increased trabecular bone in the primary spongiosa (PS), modest growth plate expansion, and increased TRAP-positive osteoclasts in the proximal tibia.
| M.Wt | 430.468 | |
| Formula | C23H22N6O3 | |
| Appearance | Solid | |
| Storage |
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| Solubility |
10 mM in DMSO |
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| Chemical Name/SMILES |
2-(2,6-dimethoxy-4-(7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl)phenyl)-5-ethyl-1,3,4-oxadiazole |
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1. Sato T, et al. Proc Natl Acad Sci U S A. 2022 Dec 13;119(50):e2214396119.
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