The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Human LOXL2 (UniProt Q9Y4K0): Functional-Annotation Research Report

Executive summary

Identity was verified before literature interpretation. LOXL2 is the human lysyl oxidase-like 2 gene product (UniProt Q9Y4K0), not a similarly named protein from another organism. The literature agrees with the supplied annotation: LOXL2 belongs to the lysyl-oxidase family and contains four N-terminal scavenger-receptor cysteine-rich (SRCR) domains followed by a conserved C-terminal lysyl-oxidase/amine-oxidase catalytic domain. No conflicting same-symbol literature was used. (meier2021oligomericstatesand pages 1-2, moon2014humanlysyloxidaselike pages 1-2)

LOXL2’s best-established primary function is extracellular: it is a secreted, copper- and lysine-tyrosylquinone (LTQ)-dependent amine oxidase that oxidatively deaminates selected lysine and hydroxylysine side chains in collagen and elastin precursors. The resulting aldehydes initiate spontaneous covalent cross-link formation, thereby stabilizing and mechanically remodeling extracellular matrix (ECM). Direct evidence is strongest for collagen IV and tropoelastin; oxidation of the extracellular domain of PDGFRβ has also been demonstrated. (meier2021oligomericstatesand pages 1-2, meier2021oligomericstatesand pages 10-12, schmelzer2019lysyloxidase–like2 pages 1-2)

LOXL2 remains a biologically credible fibrosis and cancer-stroma target, but therapeutic validation is unresolved. The anti-LOXL2 antibody simtuzumab failed in multiple phase 2 trials. Work published in 2023–2024 suggests that the antibody did not adequately inhibit catalytic cross-linking in disease-relevant models and, in some IPF models, produced counterproductive profibrotic effects. Thus, simtuzumab’s failure should not automatically be interpreted as proof that LOXL2 catalytic activity is irrelevant; it instead exposes target-engagement, model-selection, redundancy, and disease-stage problems. (espindola2023translationalstudiesreveal pages 1-2, bell2024spatialtranscriptomicvalidation pages 10-11)

Table: This table compacts the strongest available evidence for human LOXL2 functional annotation, from molecular mechanism and substrates to recent therapeutic re-evaluations. It is useful as a quick reference for separating well-established extracellular amine-oxidase functions from more tentative disease-mechanistic and translational claims.

1. Identity, nomenclature and domain verification

The target is Homo sapiens LOXL2, approved name lysyl oxidase like 2. Its architecture matches the supplied InterPro annotation:

• an N-terminal signal-peptide/secretory precursor context;
• four N-terminal SRCR domains, corresponding to the supplied SRCR and SRCR-like-superfamily assignments;
• a conserved C-terminal lysyl-oxidase catalytic region, corresponding to the supplied LOX-like protein, lysyl-oxidase, and lysyl-oxidase conserved-site annotations.

The SRCR domains distinguish LOXL2 structurally from canonical LOX while potentially organizing substrate and partner recognition. The C-terminal domain has approximately 68% sequence similarity to the corresponding LOX catalytic region and contains the conserved copper-binding and LTQ machinery. (meier2021oligomericstatesand pages 1-2)

Structural studies describe full-length LOXL2 as an elongated or rod-like protein, with the SRCR domains forming a stalk and the catalytic domain positioned at one end. Full-length protein is predominantly monomeric in solution but can form concentration-dependent oligomers: at concentrations reported as at least 0.88 mg/mL, approximately 83.6% was monomer, 11.6% dimer, and 4.7% tetramer plus pentamer. Deleting SRCR1–2 abolished the detected oligomeric species, implicating these domains in self-association. (meier2021oligomericstatesand pages 10-12, schmelzer2019lysyloxidase–like2 pages 1-2)

2. Primary biochemical function

2.1 Catalyzed reaction

LOXL2 is classified as a protein-lysine 6-oxidase/lysyl oxidase, EC 1.4.3.13. Its net reaction can be represented as:

peptidyl-L-lysine + O₂ + H₂O → peptidyl-allysine + NH₃ + H₂O₂

Hydroxylysine residues can analogously yield hydroxyallysine. These reactive aldehydes then undergo non-enzymatic condensation with neighboring lysine, hydroxylysine, or aldehyde-bearing residues to create immature and subsequently mature collagen or elastin cross-links. LOXL2 therefore initiates cross-linking chemically; it does not directly catalyze every subsequent condensation step. Its structural consequence is increased ECM stability, protease resistance, organization and—when excessive—tissue stiffness. (immanuel2024loxl2innon‐alcoholic pages 4-4, moon2014humanlysyloxidaselike pages 1-2, schmelzer2019lysyloxidase–like2 pages 1-2)

2.2 Cofactors and active site

LOXL2 requires Cu²⁺ and the protein-derived quinone cofactor LTQ. The catalytic region contains a conserved His-X-His-X-His copper-binding motif. LTQ is generated post-translationally from Lys653 and Tyr689 in the human sequence. Structural comparisons indicate that LTQ maturation does not cause a major global rearrangement of LOXL2, and the principal set of disulfide bonds is retained between precursor and mature forms. (meier2021oligomericstatesand pages 1-2, moon2014humanlysyloxidaselike pages 1-2)

Molecular oxygen is the terminal oxidant, explaining production of hydrogen peroxide. Consequently, LOXL2 couples ECM cross-link generation to local redox chemistry, although many reported downstream “redox-signaling” effects are indirect and should not be treated as part of the minimal enzyme annotation.

2.3 Substrate specificity

The defensible annotation is peptidyl lysine/hydroxylysine oxidase with preference for structured extracellular protein substrates, rather than a narrowly sequence-specific enzyme.

• Tropoelastin: Direct binding, oxidative deamination, allysine formation, and cross-linked peptides were demonstrated by biochemical and proteomic methods. The resulting elastin-like material resisted trypsin and had mechanical properties resembling mature elastin. Vascular-wall codistribution of LOXL2 and elastin supports, but does not alone prove, an in-vivo elastogenesis role. (schmelzer2019lysyloxidase–like2 pages 1-2)
• Collagen: Collagen IV is a repeatedly documented substrate. The broader literature supports collagen cross-linking as a major function, but residue-level and isoform-by-isoform specificity remains incomplete. It is therefore safer to state that LOXL2 acts on multiple collagen contexts rather than that it is universally equivalent across all 28 collagen types. (meier2021oligomericstatesand pages 1-2)
• PDGFRβ: LOXL2 can oxidize lysines in the receptor’s extracellular domain, showing that its protein-substrate scope extends beyond fibrillar structural proteins. The physiological importance of this reaction is less established than collagen/elastin cross-linking. (meier2021oligomericstatesand pages 10-12)
• Small-amolecule assay substrates: 1,5-diaminopentane and spermine support activity assays, with reported approximate values of Km ≈1 mM and kcat ≈0.02 s⁻¹. These values are useful for assay development but should not be extrapolated directly to native collagen or elastin kinetics. β-Aminopropionitrile inhibited these assay reactions with IC₅₀ values of 5.0±1.4 and 3.8±0.2 µM, respectively. (moon2014humanlysyloxidaselike pages 1-2)

3. Biosynthesis, processing and site of action

LOXL2 is synthesized as a precursor and secreted through the conventional secretory pathway as an approximately 100-kDa full-length glycoprotein. Extracellular PACE4 processing at Arg314-Phe315-Arg316-Lys317↓Ala318 removes the first two SRCR domains and yields an approximately 60-kDa form. In vitro, this cleavage does not abolish amine-oxidase activity against cadaverine or tropoelastin, although it changes solubility and oligomeric behavior. The physiological purpose of this processing remains uncertain. (meier2021oligomericstatesand pages 1-2)

The strongest localization/function assignment is therefore the extracellular space and ECM, particularly sites of collagen and elastin maturation or pathological matrix deposition. Secreted LOXL2 can associate with vascular elastin, basement-membrane collagen, cell-surface receptors and other matrix partners. The SRCR domains likely contribute to localization, substrate presentation and protein interactions rather than housing the catalytic chemistry. (meier2021oligomericstatesand pages 10-12, schmelzer2019lysyloxidase–like2 pages 1-2)

Intracellular and nuclear LOXL2 pools have been reported in cancer and EMT studies, including proposed regulation of transcription, histones and signaling. These observations may be biologically important, but they are less consistently defined mechanistically than extracellular oxidation. Some alleged intracellular functions may also be catalytic-activity-independent. They should therefore be represented as context-dependent secondary functions, not as replacements for the primary extracellular amine-oxidase annotation. (immanuel2024loxl2innon‐alcoholic pages 4-4)

4. Biological pathways and processes

4.1 ECM assembly and mechanobiology

By introducing aldehydes into collagen and elastin, LOXL2 controls cross-link density, fibril/fiber architecture, matrix insolubility and stiffness. These material changes affect integrin engagement, focal adhesion signaling, cytoskeletal tension and fibroblast-to-myofibroblast differentiation. Thus, many effects attributed to “LOXL2 signaling” are better understood as a sequence:

LOXL2 secretion → lysine/hydroxylysine oxidation → ECM cross-linking/stiffening → altered receptor engagement and mechanotransduction.

This distinction matters because downstream proliferation, migration or transcriptional changes may result from matrix mechanics rather than direct intracellular signaling by LOXL2.

4.2 Fibrosis

LOXL2 is frequently elevated in fibrotic tissues and contributes to persistence of collagen-rich scar matrix. A 2024 NASH review identifies hepatic stellate-cell activation, ECM cross-linking, oxidative stress and altered inflammatory/metabolic states as interconnected LOXL2-associated processes. However, direct enzymatic cross-linking is the most secure mechanism; effects on lipid metabolism or inflammation may be secondary or context-specific. (immanuel2024loxl2innon‐alcoholic pages 4-4)

Open Targets associates human LOXL2 with idiopathic pulmonary fibrosis, although the displayed aggregate association score is modest (approximately 0.119) and reflects heterogeneous evidence. Database association scores should not be confused with causal effect sizes or clinical efficacy. (OpenTargets Search: -LOXL2)

4.3 Cancer and metastasis

In tumors, LOXL2-mediated collagen cross-linking can align and stiffen the matrix, facilitate invasion, compress vessels, limit drug penetration and remodel immune-cell access. Increased LOXL2 has accordingly been linked to desmoplasia, EMT-like states and metastasis. Nevertheless, cancer phenotypes are not uniformly catalytic or cell autonomous: macrophage-, fibroblast- and tumor-cell-derived LOXL2 can have different effects, and other LOX-family enzymes may compensate.

The clinically relevant interpretation is therefore that LOXL2 is a matrix-remodeling node, not a simple universal oncogenic switch. Its value is likely to depend on tumor type, producing cell, substrate environment, disease stage and combination therapy.

5. Recent developments, emphasizing 2023–2024

5.1 Re-evaluation of anti-LOXL2 therapy in pulmonary fibrosis

Espindola and colleagues, published November 2023, found elevated LOXL2 transcript and protein in IPF lungs. Slow-progressing IPF fibroblasts showed an approximately fourfold transcript increase relative to normal cells, while SSEA4-positive progenitors showed about 2.4–3.1-fold increases in slow- and rapid-IPF groups. Despite this association, simtuzumab did not reduce collagen production or fibroblast migration as nintedanib did; instead, it promoted myofibroblast differentiation and invasion in some assays. Preventive or delayed dosing at 15 mg/kg twice weekly worsened fibrosis in a humanized mouse model. Human-cell experiments included normal and IPF fibroblasts at n=4 per group, while mouse groups were small (n=3–5), so the direction of effect is important but precise effect-size generalization is limited. [Published November 2023; DOI: https://doi.org/10.35534/fibrosis.2023.10007] (espindola2023translationalstudiesreveal pages 6-8, espindola2023translationalstudiesreveal pages 1-2, espindola2023translationalstudiesreveal pages 18-21)

Bell and colleagues, published September 2024, used spatial transcriptomics to validate a three-dimensional fibrosis model against human fibroblast foci. In this disease-relevant system, AB0023—the precursor antibody to simtuzumab—did not significantly inhibit LOXL2 catalytic activity, collagen cross-linking or tissue stiffness. This finding challenges the assumption that prior antibody trials rigorously tested catalytic LOXL2 inhibition. [Published September 2024; DOI: https://doi.org/10.1016/j.xcrm.2024.101695] (bell2024spatialtranscriptomicvalidation pages 10-11)

Expert interpretation: these studies suggest at least three non-exclusive explanations for clinical failure: insufficient catalytic target engagement, potentially agonistic or compensatory effects of antibody binding, and biological redundancy among LOX-family enzymes. They also illustrate why target expression alone is an inadequate biomarker for response.

5.2 Other 2023–2024 directions

Recent work extends LOXL2 research beyond simple collagen abundance toward spatially resolved matrix architecture, cell-specific sources, and catalytic versus non-catalytic functions. Examples include macrophage-driven LOXL2 programs in pancreatic cancer, pan-LOX inhibition to decompress tumor vessels and improve chemotherapy, and proposed non-enzymatic LOXL2/HIF1A effects in ligament vascularization. These findings are promising mechanistic leads, but most remain preclinical and cannot yet be described as established human therapy.

The emerging consensus is that small-molecule catalytic inhibitors with verified tissue pharmacodynamics may provide a cleaner test than antibodies directed to non-catalytic SRCR epitopes. Conversely, pan-LOX inhibition may better overcome family redundancy but carries a greater risk of disturbing physiological collagen and elastin homeostasis.

6. Applications and real-world implementation

6.1 Drug development

No LOXL2 or pan-LOX inhibitor is established as an approved therapy in the evidence reviewed. Clinical development has included:

• Simtuzumab/GS-6624, an anti-LOXL2 antibody. The randomized phase 2 RAINIER IPF study enrolled 544 participants and was terminated for lack of efficacy. Its endpoints included progression-free survival based on confirmed FVC decline or death, including analyses stratified by serum LOXL2. [NCT01769196; posted results April 13, 2017: https://clinicaltrials.gov/study/NCT01769196] (NCT01769196 chunk 1)
• In primary sclerosing cholangitis, a randomized phase 2b trial enrolled 235 participants receiving 75 mg, 125 mg or placebo weekly for 96 weeks. [NCT01672853: https://clinicaltrials.gov/study/NCT01672853] (NCT01672853 chunk 1)
• In metastatic pancreatic adenocarcinoma, simtuzumab plus gemcitabine was tested in a phase 2 study enrolling 250 participants. [NCT01472198: https://clinicaltrials.gov/study/NCT01472198] (NCT01472198 chunk 1)
• In KRAS-mutant metastatic colorectal cancer, simtuzumab plus FOLFIRI was tested in a phase 2 study enrolling 266 participants; the study was terminated. [NCT01479465: https://clinicaltrials.gov/study/NCT01479465] (NCT01479465 chunk 1)
• GB2064/PAT-1251, described as a high-affinity, selective, mechanism-based oral LOXL2 inhibitor, entered an open-label phase IIa myelofibrosis study at 1,000 mg twice daily, with 21 participants listed and active-not-recruiting status in the retrieved April 2024 record. [NCT04679870; last posted April 3, 2024: https://clinicaltrials.gov/study/NCT04679870] (NCT04679870 chunk 1)
• PXS-5505/amsulostat, a pan-LOX inhibitor, entered a phase 1/2a myelofibrosis program with 43 actual participants, including monotherapy and ruxolitinib add-on cohorts. Its pharmacodynamic endpoints explicitly include plasma LOX/LOXL2 inhibition and changes in reticulin and collagen marrow fibrosis. Because it is pan-family rather than LOXL2-selective, outcomes cannot isolate LOXL2 alone. [NCT04676529: https://clinicaltrials.gov/study/NCT04676529] (NCT04676529 chunk 1)

6.2 Biomarkers

LOXL2 protein, transcript abundance, serum LOXL2 and matrix cross-link signatures have been explored as fibrosis or cancer biomarkers. Current evidence supports association more strongly than clinical utility. Serum abundance may not report local catalytic activity, substrate accessibility or drug engagement; future biomarkers should combine enzyme-activity measures with tissue cross-link chemistry and mechanical readouts.

6.3 Biomaterials and tissue engineering

Recombinant LOXL2 can cross-link tropoelastin into protease-resistant, mechanically mature-elastin-like material under cell-compatible conditions. This provides a concrete application in engineered elastic tissues, vascular constructs and biomimetic matrices, although manufacturing control, residual peroxide, cross-link uniformity and immunogenicity require evaluation. [Published January 2019; DOI: https://doi.org/10.1096/fj.201801860rr] (schmelzer2019lysyloxidase–like2 pages 1-2)

7. Evidence assessment and annotation recommendations

High-confidence annotation

1. Human LOXL2/Q9Y4K0 is a secreted lysyl-oxidase-family precursor with four SRCR domains and a C-terminal catalytic domain.
2. It is a Cu²⁺/LTQ-dependent amine oxidase using oxygen to convert peptidyl lysine or hydroxylysine into aldehydes, with ammonia and hydrogen peroxide as coproducts.
3. Its principal site of action is extracellular.
4. Collagen and tropoelastin are physiological substrate classes; direct tropoelastin cross-linking and collagen-IV oxidation are experimentally supported.
5. The principal biological role is initiation of ECM cross-linking and regulation of matrix stability and mechanics.

Moderate-confidence/context-dependent annotation

• oxidation of non-matrix extracellular proteins such as PDGFRβ;
• regulation of EMT, angiogenesis and immune behavior downstream of ECM mechanics;
• intracellular or nuclear functions, including chromatin-associated effects;
• disease-specific causal roles inferred mainly from expression correlations or perturbation models.

Important unresolved questions

• Which lysine/hydroxylysine positions and collagen isoforms are preferred in vivo?
• What is the physiological significance of PACE4 removal of SRCR1–2?
• Which reported intracellular activities require the LTQ/copper catalytic mechanism?
• Can selective catalytic inhibition achieve adequate tissue exposure without compensation by LOX, LOXL1, LOXL3 or LOXL4?
• Which activity-based or cross-link biomarkers best identify patients likely to benefit?

Conclusion

The most defensible functional annotation of human LOXL2 is a secreted copper/LTQ-dependent protein-lysine oxidase that initiates collagen and elastin cross-linking in the extracellular matrix. Its direct chemistry is well established; many fibrosis, cancer, angiogenesis and EMT phenotypes are downstream consequences of altered matrix architecture or context-dependent non-catalytic functions. The 2023–2024 literature has shifted emphasis from simple LOXL2 expression toward catalytic target engagement, spatially faithful human models, family redundancy and cell-specific matrix biology. Simtuzumab’s failures substantially weaken that antibody strategy but do not constitute a definitive test of selective catalytic LOXL2 inhibition.

References

1. (meier2021oligomericstatesand pages 1-2): Alex A. Meier, Hee-Jung Moon, Ronald Toth, Ewa Folta-Stogniew, Krzysztof Kuczera, C. Russell Middaugh, and Minae Mure. Oligomeric states and hydrodynamic properties of lysyl oxidase-like 2. Dec 2021. URL: https://doi.org/10.3390/biom11121846, doi:10.3390/biom11121846. This article has 7 citations.

2. (moon2014humanlysyloxidaselike pages 1-2): Hee-Jung Moon, Joel Finney, Trey Ronnebaum, and Minae Mure. Human lysyl oxidase-like 2. Bioorganic chemistry, 57:231-41, Dec 2014. URL: https://doi.org/10.1016/j.bioorg.2014.07.003, doi:10.1016/j.bioorg.2014.07.003. This article has 196 citations and is from a peer-reviewed journal.

3. (meier2021oligomericstatesand pages 10-12): Alex A. Meier, Hee-Jung Moon, Ronald Toth, Ewa Folta-Stogniew, Krzysztof Kuczera, C. Russell Middaugh, and Minae Mure. Oligomeric states and hydrodynamic properties of lysyl oxidase-like 2. Dec 2021. URL: https://doi.org/10.3390/biom11121846, doi:10.3390/biom11121846. This article has 7 citations.

4. (schmelzer2019lysyloxidase–like2 pages 1-2): Christian E. H. Schmelzer, Andrea Heinz, Helen Troilo, Michael P. Lockhart‐Cairns, Thomas A. Jowitt, Marion F. Marchand, Laurent Bidault, Marine Bignon, Tobias Hedtke, Alain Barret, James C. McConnell, Michael J. Sherratt, Stéphane Germain, David J. S. Hulmes, Clair Baldock, and Laurent Muller. Lysyl oxidase–like 2 (loxl2)–mediated cross-linking of tropoelastin. The FASEB Journal, 33:5468-5481, Jan 2019. URL: https://doi.org/10.1096/fj.201801860rr, doi:10.1096/fj.201801860rr. This article has 94 citations.

5. (espindola2023translationalstudiesreveal pages 1-2): Milena S. Espindola, David M. Habiel, Ana Lucia Coelho, Tanyalak Parimon, Peter Chen, Amanda Mikels-Vigdal, and Cory M. Hogaboam. Translational studies reveal the divergent effects of simtuzumab targeting loxl2 in idiopathic pulmonary fibrosis. Fibrosis (Hong Kong, China), 1:1-12, Nov 2023. URL: https://doi.org/10.35534/fibrosis.2023.10007, doi:10.35534/fibrosis.2023.10007. This article has 13 citations.

6. (bell2024spatialtranscriptomicvalidation pages 10-11): Joseph A. Bell, Elizabeth R. Davies, Christopher J. Brereton, Milica Vukmirovic, James J.W. Roberts, Kerry Lunn, Leanne Wickens, Franco Conforti, Robert A. Ridley, Jessica Ceccato, Lucy N. Sayer, David A. Johnston, Andres F. Vallejo, Aiman Alzetani, Sanjay Jogai, Ben G. Marshall, Aurelie Fabre, Luca Richeldi, Phillip D. Monk, Paul Skipp, Naftali Kaminski, Emily Offer, Yihua Wang, Donna E. Davies, and Mark G. Jones. Spatial transcriptomic validation of a biomimetic model of fibrosis enables re-evaluation of a therapeutic antibody targeting loxl2. Sep 2024. URL: https://doi.org/10.1016/j.xcrm.2024.101695, doi:10.1016/j.xcrm.2024.101695. This article has 20 citations and is from a peer-reviewed journal.

7. (immanuel2024loxl2innon‐alcoholic pages 4-4): Joys Rachel Immanuel, Rajnish Kumar, Ashish Kumar Agrahari, and Shailendra Asthana. Loxl2 in non‐alcoholic steatohepatitis (nash): insights into fibrosis pathogenesis and therapeutic potential. Liver International Communications, Mar 2024. URL: https://doi.org/10.1002/lci2.85, doi:10.1002/lci2.85. This article has 4 citations.

8. (OpenTargets Search: -LOXL2): Open Targets Query (-LOXL2, 5 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.

9. (espindola2023translationalstudiesreveal pages 6-8): Milena S. Espindola, David M. Habiel, Ana Lucia Coelho, Tanyalak Parimon, Peter Chen, Amanda Mikels-Vigdal, and Cory M. Hogaboam. Translational studies reveal the divergent effects of simtuzumab targeting loxl2 in idiopathic pulmonary fibrosis. Fibrosis (Hong Kong, China), 1:1-12, Nov 2023. URL: https://doi.org/10.35534/fibrosis.2023.10007, doi:10.35534/fibrosis.2023.10007. This article has 13 citations.

10. (espindola2023translationalstudiesreveal pages 18-21): Milena S. Espindola, David M. Habiel, Ana Lucia Coelho, Tanyalak Parimon, Peter Chen, Amanda Mikels-Vigdal, and Cory M. Hogaboam. Translational studies reveal the divergent effects of simtuzumab targeting loxl2 in idiopathic pulmonary fibrosis. Fibrosis (Hong Kong, China), 1:1-12, Nov 2023. URL: https://doi.org/10.35534/fibrosis.2023.10007, doi:10.35534/fibrosis.2023.10007. This article has 13 citations.

11. (NCT01769196 chunk 1): Study to Assess the Efficacy and Safety of Simtuzumab (GS-6624) in Adults With Idiopathic Pulmonary Fibrosis (IPF). Gilead Sciences. 2013. ClinicalTrials.gov Identifier: NCT01769196

12. (NCT01672853 chunk 1): Simtuzumab (GS-6624) in the Prevention of Progression of Liver Fibrosis in Adults With Primary Sclerosing Cholangitis (PSC). Gilead Sciences. 2013. ClinicalTrials.gov Identifier: NCT01672853

13. (NCT01472198 chunk 1): A Study to Evaluate the Efficacy and Safety of Simtuzumab Combined With Gemcitabine for Metastatic Pancreatic Adenocarcinoma. Gilead Sciences. 2011. ClinicalTrials.gov Identifier: NCT01472198

14. (NCT01479465 chunk 1): Efficacy and Safety of Simtuzumab (SIM) With FOLFIRI as Second Line Treatment in Colorectal Adenocarcinoma. Gilead Sciences. 2011. ClinicalTrials.gov Identifier: NCT01479465

15. (NCT04679870 chunk 1): A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Oral GB2064 in Participants With Myelofibrosis. Galecto Biotech AB. 2021. ClinicalTrials.gov Identifier: NCT04679870

16. (NCT04676529 chunk 1): Study to Evaluate Safety, Pharmacokinetic and Pharmacodynamic Dose Escalation and Expansion Study of PXS-5505 in Patients With Primary, Post-polycythemia Vera or Post-essential Thrombocythemia Myelofibrosis. Syntara. 2021. ClinicalTrials.gov Identifier: NCT04676529

Artifacts

• Edison artifact artifact-00

Citations

1. meier2021oligomericstatesand pages 1-2
2. meier2021oligomericstatesand pages 10-12
3. moon2014humanlysyloxidaselike pages 1-2
4. bell2024spatialtranscriptomicvalidation pages 10-11
5. espindola2023translationalstudiesreveal pages 1-2
6. espindola2023translationalstudiesreveal pages 6-8
7. espindola2023translationalstudiesreveal pages 18-21
8. Published November 2023; DOI: https://doi.org/10.35534/fibrosis.2023.10007
9. Published September 2024; DOI: https://doi.org/10.1016/j.xcrm.2024.101695
10. NCT01769196; posted results April 13, 2017: https://clinicaltrials.gov/study/NCT01769196
11. NCT01672853: https://clinicaltrials.gov/study/NCT01672853
12. NCT01472198: https://clinicaltrials.gov/study/NCT01472198
13. NCT01479465: https://clinicaltrials.gov/study/NCT01479465
14. NCT04679870; last posted April 3, 2024: https://clinicaltrials.gov/study/NCT04679870
15. NCT04676529: https://clinicaltrials.gov/study/NCT04676529
16. Published January 2019; DOI: https://doi.org/10.1096/fj.201801860rr
17. https://doi.org/10.35534/fibrosis.2023.10007]
18. https://doi.org/10.1016/j.xcrm.2024.101695]
19. https://clinicaltrials.gov/study/NCT01769196]
20. https://clinicaltrials.gov/study/NCT01672853]
21. https://clinicaltrials.gov/study/NCT01472198]
22. https://clinicaltrials.gov/study/NCT01479465]
23. https://clinicaltrials.gov/study/NCT04679870]
24. https://clinicaltrials.gov/study/NCT04676529]
25. https://doi.org/10.1096/fj.201801860rr]
26. https://doi.org/10.3390/biom11121846,
27. https://doi.org/10.1016/j.bioorg.2014.07.003,
28. https://doi.org/10.1096/fj.201801860rr,
29. https://doi.org/10.35534/fibrosis.2023.10007,
30. https://doi.org/10.1016/j.xcrm.2024.101695,
31. https://doi.org/10.1002/lci2.85,