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Fgfr3
FGFR3 is a fibroblast growth factor receptor whose constitutively active mutation causes achondroplasia (most common dwarfism).
Aliases (5)
Overview
What is Fgfr3?
FGFR3 (Fibroblast Growth Factor Receptor 3) is a receptor tyrosine kinase involved in bone growth, hair follicle cycling, and cellular signaling. As a research target, FGFR3-modulating compounds and peptides are explored for hair loss, cartilage disorders, and certain cancers.
Key Benefits
FGFR3 modulators are investigated for treatment of achondroplasia (loss-of-function approaches), hair regrowth (gain-of-function in follicle), and oncology (FGFR3-driven tumors). Not yet a consumer compound.
Mechanism of Action
FGFR3 is a transmembrane receptor tyrosine kinase activated by fibroblast growth factors. Downstream signaling via RAS-MAPK and PI3K-AKT regulates chondrocyte proliferation, hair follicle stem cells, and cell survival.
Pharmacokinetics
What to Expect
- Week 1Tolerability and dose-response.
- Week 2-4Early effect window.
- Week 4-8Peak benefit assessment.
- Week 8+Cycle decision point.
Side Effects & Safety
- Common (>10%): Vosoritide — injection site reaction, transient mild hypotension, dizziness. TKIs — hyperphosphatemia, GI upset, retinal pigment epithelial detachment.
- Less common (1-10%): Vomiting, fatigue (vosoritide). TKIs — hand-foot syndrome, nail toxicity, transaminitis.
- Rare-serious (<1%): TKIs in oncology dose — serous retinal detachment, severe hyperphosphatemia, cardiotoxicity.
- Specific watch periods: Vosoritide — first 30 min post-injection for symptomatic hypotension; long-term — joint growth proportions monitored.
References
Savarirayan R, et al. (2020) — Once-daily, subcutaneous vosoritide therapy in children with achondroplasia: a randomised, double-blind, phase 3, placebo-controlled, multicentre trial. Lancet
PMID 32945803, vosoritide pivotal trial
View StudySavarirayan R, et al. (2022) — Vosoritide for children with achondroplasia: a 30-month update from an ongoing extension study. Genetics in Medicine
PMID 35305862, long-term extension
View StudyKomla-Ebri D, et al. (2016) — Tyrosine kinase inhibitor NVP-BGJ398 functionally improves FGFR3-related dwarfism in mouse model. J Clin Invest
PMID 27348590, infigratinib mechanism in achondroplasia model
View StudyGoyal L, et al. (2023) — Futibatinib for FGFR2-rearranged intrahepatic cholangiocarcinoma. NEJM
PMID 36534649, futibatinib (sotuletinib alias) oncology pivotal — confirms it is NOT an achondroplasia drug
View StudyForeman PK, et al. (2020) — Birth prevalence of achondroplasia: a systematic literature review. Am J Med Genet A
PMID 32243066, epidemiologic context
View StudyHow was your experience with this compound?
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