Target intelligence / Profile preview

Hyaluronan (HA) (HA)

Target
HA
Molecular classification
Glycosaminoglycan, Polysaccharide, Extracellular matrix component
01

Overview

Hyaluronan (HA) is a high-molecular-weight, non-sulfated glycosaminoglycan that serves as a fundamental structural component of the extracellular matrix (ECM) (PubMed, PMID: 30205510). It is synthesized by hyaluronan synthases (HAS1-3) at the plasma membrane and plays a vital role in maintaining tissue hydration, lubrication, and mechanical integrity (NCBI, NBK279354). HA acts as a ligand for receptors like CD44 and RHAMM, triggering signaling pathways that govern cell proliferation, migration, and wound healing (Nature Reviews Cancer, 2019). In pathological states, particularly in desmoplastic tumors like pancreatic cancer, HA accumulation leads to elevated interstitial fluid pressure, which impairs vascular perfusion and limits the efficacy of systemic therapies (Journal of Clinical Oncology, 2020). Therapeutic interventions include the use of hyaluronidases to degrade the ECM barrier and improve drug penetration or the administration of exogenous HA for the treatment of osteoarthritis (StatPearls, 2023).

Other names
Hyaluronic acidHyaluronateNonsulfated glycosaminoglycan
02

Mechanism of action

Enzymatic degradation of hyaluronan to reduce interstitial fluid pressure and enhance drug delivery (PubMed, PMID: 29610301); inhibition of hyaluronan synthases to prevent pathological accumulation; supplementation of high-molecular-weight hyaluronan to restore joint lubrication (StatPearls, 2023).

03

Biological functions

Tissue hydrationCell migrationCell proliferationLubricationSignal transductionWound healing
04

Disease associations

CancerInflammationOsteoarthritisFibrosisEdema
05

Safety considerations

Musculoskeletal pain and arthralgia (ClinicalTrials.gov, NCT02715804)Increased risk of thromboembolic eventsPotential for facilitating tumor metastasis if low-molecular-weight fragments accumulateInjection site reactions
06

Interacting drugs

Pegvorhyaluronidase alfa (PEGPH20)

3 more in the full profile.

07

Biomarkers

HA-high tumor status (via immunohistochemistry)Serum hyaluronan concentrationCD44 receptor expression levels

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