ArticleeLife2021
Dual targeting of salt inducible kinases and CSF1R uncouples bone formation and bone resorption.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 23 citations in OpenAlex.
- Salt-inducible kinases as druggable targets for immunotherapy of ovarian cancer.Nature immunology · 2026Article
- Inhibition of salt-inducible kinases reprograms T cells and antitumor immunity in ovarian cancer.Nature immunology · 2026Article
- The orally available SIK2/SIK3 inhibitor SK-124 increases bone mass in hypogonadal male mice.JBMR plus · 2026Article
- MicroRNA-128-3p Deficiency Alleviates Bone Loss in Age-Related Osteoporosis via Activation of Canonical Wnt Signaling.Aging cell · 2026Article
- Control of alveolar bone development, homeostasis, and socket healing by salt-inducible kinases.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2025Article
- Salt-inducible Kinase Regulation of Adipose Tissue Metabolism.Endocrinology · 2025Review
- Identification of highly selective SIK1/2 inhibitors that modulate innate immune activation and suppress intestinal inflammation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Stimulation of fracture mineralization by salt-inducible kinase inhibitors.Frontiers in bioengineering and biotechnology · 2024Article
- Understanding the roles of salt-inducible kinases in cardiometabolic disease.Frontiers in physiology · 2024Review
- The multiple roles of salt-inducible kinases in regulating physiology.Physiological reviews · 2023Review
- Targeting strategies for bone diseases: signaling pathways and clinical studies.Signal transduction and targeted therapy · 2023Review
- A parathyroid hormone/salt-inducible kinase signaling axis controls renal vitamin D activation and organismal calcium homeostasis.The Journal of clinical investigation · 2023Article
- Structure-based design of selective, orally available salt-inducible kinase inhibitors that stimulate bone formation in mice.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
Corrections and comments
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Authors and funding
26 authors at 10 institutions in 4 countries.
Funding
Abstract
Bone formation and resorption are typically coupled, such that the efficacy of anabolic osteoporosis treatments may be limited by bone destruction. The multi-kinase inhibitor YKL-05-099 potently inhibits salt inducible kinases (SIKs) and may represent a promising new class of bone anabolic agents. Here, we report that YKL-05-099 increases bone formation in hypogonadal female mice without increasing bone resorption. Postnatal mice with inducible, global deletion of SIK2 and SIK3 show increased bone mass, increased bone formation, and, distinct from the effects of YKL-05-099, increased bone resorption. No cell-intrinsic role of SIKs in osteoclasts was noted. In addition to blocking SIKs, YKL-05-099 also binds and inhibits CSF1R, the receptor for the osteoclastogenic cytokine M-CSF. Modeling reveals that YKL-05-099 binds to SIK2 and CSF1R in a similar manner. Dual targeting of SIK2/3 and CSF1R induces bone formation without concomitantly increasing bone resorption and thereby may overcome limitations of most current anabolic osteoporosis therapies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.