Target intelligence / Profile preview

Bone morphogenetic protein receptor type 1B (BMPR1B) (ALK6)

Target
ALK6
Molecular classification
Receptor, Serine/threonine-protein kinase, Transforming growth factor beta receptor family, Type I receptor
01

Overview

Bone morphogenetic protein receptor type 1B (BMPR1B), also known as ALK6, is a transmembrane serine/threonine kinase that serves as a type I receptor for the bone morphogenetic protein (BMP) signaling pathway. It is a member of the transforming growth factor-beta (TGF-beta) receptor superfamily and plays a pivotal role in embryonic development, particularly in limb patterning, chondrogenesis, and the formation of the nervous system. Beyond development, ALK6 is essential for regulating ovarian follicle maturation and bone homeostasis in adults. In the context of disease, mutations in the BMPR1B gene are linked to skeletal abnormalities such as brachydactyly and acromesomelic dysplasia, while its dysregulation is implicated in various cancers, including breast and ovarian malignancies. In some cancers, ALK6 acts as an oncogene promoting tumor progression, whereas in others, its loss is associated with increased malignancy. Therapeutic interest in ALK6 focuses on the development of small-molecule kinase inhibitors and ligand-trapping agents to modulate BMP signaling, although achieving high selectivity over other closely related ALK receptors remains a primary challenge for drug discovery.

Other names
Activin receptor-like kinase 6ALK-6CDw293AMDDBDA1DBDA2AMD3Serine/threonine receptor kinase
02

Mechanism of action

Inhibition of kinase activity, blocking ligand binding, or activation of SMAD-dependent signaling through ligand binding.

03

Biological functions

Signal transductionBone developmentChondrogenesisOocyte developmentCell proliferationCell differentiationApoptosisNeural crest development
04

Disease associations

CancerBrachydactylyAcromesomelic dysplasiaPrimary ovarian insufficiencyPulmonary hypertensionSkeletal malformation
05

Safety considerations

Off-target inhibition of other ALK family members (e.g., ALK2, ALK3)Potential impact on fertility and ovarian functionDisruption of bone homeostasisRisk of heterotopic ossification if over-activated
06

Interacting drugs

LDN-193189

6 more in the full profile.

07

Biomarkers

BMPR1B expression levelPhosphorylated SMAD1/5/8 (p-SMAD1/5/8)

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