Simtuzumab
Based on 1 Customer Validation
Simtuzumab (AB 0024; GS 6624) is a monoclonal antibody directed against Lysyl oxidase like-2 (LOXL2). Simtuzumab non-competitively blocks collagen cross-linking, reduces LOXL2 protein expression and attenuates extracellular matrix changes. Simtuzumab reduces myocardial fibrosis and prevents cardiac dysfunction. Simtuzumab lowers Myh7 and Nppa gene expression, reduces contraction heterogeneity, and cuts COL1A1 deposition. Simtuzumab can be used for the research of LMNA mutation-induced dilated cardiomyopathy, idiopathic pulmonary fibrosis, and primary sclerosing cholangitis.
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- Purity: ≥99.0%
- CAS No.: 1318075-13-6
- 분자량:145.5 kDa
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보관:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- 순도&문서
- References
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Help & FAQs
Biological Activity
Human IgG4 kappa
Human
LOXL2
Simtuzumab (1 µM; 15 days) reduces contraction heterogeneity, contraction time, diastolic time, and COL1A1 deposition area in LMNAH222P hiPSC-CMs, without altering contraction amplitude[1].
Simtuzumab (1-50 μg/mL; 72 h) enhances myofibroblast differentiation in primary IPF human lung fibroblasts at 50 μg/mL, particularly with IL-13 stimulation, and induces mild differentiation in primary normal human lung fibroblasts at the same dose without additional stimuli[2].
Simtuzumab (50 μg/mL; 7 day) does not reduce or alter collagen 1 synthesis in primary normal or IPF human lung fibroblasts, even with pro-fibrotic stimuli[2].
Simtuzumab (50 μg/mL; 96 h) increases the invasive migration of primary normal and IPF human lung fibroblasts in a scratch wound assay[2].
Simtuzumab (50 μg/mL; 26 days, replenished twice weekly) accelerates the outgrowth of primary fibroblasts from mixed normal and IPF human lung explant cells and increases the expression of fibrosis-related genes in these cultures[2].
Simtuzumab (50 μg/mL; 24 h) increases αSMA and Collagen 3 transcript expression in SSEA4+-enriched mesenchymal progenitors from normal human lung samples[2].
Simtuzumab (50 μg/mL; 10 days, replenished every 3 days) increases LOXL2 and PDGFRA transcript expression and induces mesenchymal-like morphological changes in mixed primary cells from normal and IPF human lung explants[2].
Simtuzumab inhibits human LOXL2 enzymatic activity, blocks fibroblast activation, and reduces LOXL2-mediated extracellular matrix modifications in in vitro assays[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:primary IPF human lung fibroblasts
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Concentration:1 μg/mL; 10 μg/mL; 50 μg/mL
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Incubation Time:72 h
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Result:Enhanced myofibroblast differentiation at 50 μg/mL with IL-13 stimulation.
Induced mild differentiation in primary normal human lung fibroblasts at 50 μg/mL without additional stimuli.
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Cell Line:primary normal and IPF human lung fibroblasts
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Concentration:50 μg/mL
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Incubation Time:7 days
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Result:Did not reduce or alter collagen 1 synthesis.
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Cell Line:primary normal and IPF human lung fibroblasts
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Concentration:50 μg/mL
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Incubation Time:96 h
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Result:Increased the invasive migration.
Simtuzumab (15 mg/kg; i.v.; twice a week; 35 days (preventative); 28 days (therapeutic)) fails to modulate lung fibrosis in a humanized NSG mouse model of idiopathic pulmonary fibrosis, with no significant differences in key fibrotic endpoints compared to IgG control, though it increases lung hydroxyproline levels relative to naive or cell-only groups and elevates SCA1+ mesenchymal progenitors in the preventative regimen[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:LmnaH222P/H222P (male, 4 months old at treatment initiation, homozygous genetic model with established cardiac disease phenotype)[1]
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Dosage:5 mg/kg
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Administration:i.p.; 3× weekly; 1 month
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Result:Reduced Loxl2 protein expression in mouse hearts.
Decreased myocardial fibrosis as shown by Sirius red staining.
Stabilized left ventricular end-diastolic diameter (LVEDd) at ~3.5 mm from 4 to 5 months, compared to an increase from 3.5 mm to 4.1 mm in untreated mice.
Preserved ejection fraction (EF) from 70.9% at 4 months to 67.1% at 5 months, compared to a decline from 67.8% to 50.0% in untreated mice.
Maintained fractional shortening from 39.6% at 4 months to 36.5% at 5 months, compared to a decline from 37.2% to 25.1% in untreated mice.
Lowered mRNA expression of cardiac stress markers Myh7 and Nppa in mouse hearts.
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Animal Model:NOD Cg-PrkdcSCID IL2rgTm1wil Szi (NSG) (6- to 8-week-old, female, pathogen-free, humanized model induced by intravenous injection of ~1×106 IPF lung cells)[2]
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Dosage:15 mg/kg
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Administration:i.v.; twice a week; 35 days (preventative); 28 days (therapeutic)
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Result:Significantly increased lung hydroxyproline levels compared to mice that received IPF cells alone in the preventative treatment group, but showed no difference compared to IgG-treated mice.
Significantly increased total lung hydroxyproline levels compared to naive mice in the therapeutic treatment group, but showed no difference compared to IgG-treated mice.
Significantly increased SCA1+ mesenchymal progenitors in bronchoalveolar lavage fluid compared to IgG-treated mice at day 35 of the preventative regimen.
Showed no significant differences compared to IgG-treated groups in fibrosis-related lung transcripts, αSMA+ cell counts, collagen intensity, or histological appearance at day 63.
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Unconjugated
The product can be reconstituted/diluted with sterile PBS or saline.
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Human IgG4 kappa
ELISA, FACS, Functional assay
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Immobilized LOXL2 Protein, Human (HEK293, His, HY-P74770) can bind Simtuzumab. The EC50 for this effect is 9.679 ng/mL. -
Flow cytometric analysis of 1X106 A549 cells with Simtuzumab (HY-P99047, red). Cells were fixed with 4% paraformaldehyde. Then stained with the primary antibody at 1/200 dilution for an hour at 4℃. AF 488-conjugated AffiniPure Goat Anti-Human IgG H&L (HY-P83776) was used as the secondary antibody at 1/1,000 dilution for 30 minutes at 4℃. Human IgG4 kappa (HY-P99003, blue) was used as the isotype control.
Chemical Information
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CAS No. 1318075-13-6
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Appearance Liquid
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분자량 145.5 kDa
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Color Colorless to light yellow
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SMILES
[Simtuzumab]
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Synonyms
AB 0024; GS 6624
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선적
Shipping with dry ice.
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Formulation
Please refer to the lot-specific COA for specific buffer information.
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보관
Please store the product under the recommended conditions in the Certificate of Analysis.
순도&문서
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Data Sheet (279 KB)
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SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Portuguese - PT (251 KB)
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Inhibitory Antibodies User Guide (603 KB)
References
[1]. Kervella M, et al. Simtuzumab Attenuates Loxl2-Mediated Extracellular Matrix Remodeling and Preserves Cardiac Function in LMNA Mutation-Induced Dilated Cardiomyopathy. Circ Heart Fail. 2026;19(4):e013806. [Content Brief]
[2]. Espindola MS, et al. Translational Studies Reveal the Divergent Effects of Simtuzumab Targeting LOXL2 in Idiopathic Pulmonary Fibrosis. Fibrosis (Hong Kong). 2023;1(2):10007. [Content Brief]
[3]. Harrison SA, et al. Simtuzumab Is Ineffective for Patients With Bridging Fibrosis or Compensated Cirrhosis Caused by Nonalcoholic Steatohepatitis. Gastroenterology. 2018;155(4):1140-1153. [Content Brief]
[4]. Verstovsek S, et al. A phase 2 study of simtuzumab in patients with primary, post-polycythaemia vera or post-essential thrombocythaemia myelofibrosis. Br J Haematol. 2017;176(6):939-949. [Content Brief]
[5]. Chen W, et al. Lysyl Oxidase (LOX) Family Members: Rationale and Their Potential as Therapeutic Targets for Liver Fibrosis. Hepatology. 2020;72(2):729-741. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Simtuzumab Related Classifications
Cat. No.: HY-P99047
Powered by Bioz
- Simtuzumab
- 1318075-13-6
- AB 0024
- GS 6624
- AB0024
- AB-0024
- GS6624
- GS 6624
- GS-6624
- Monoamine Oxidase
- collagen cross-linking
- myocardial fibrosis
- LMNA mutation-induced dilated cardiomyopathy
- idiopathic pulmonary fibrosis
- hiPSC-CMs
- mouse LOXL2
- human LOXL2
- primary sclerosing cholangitis
- LOXL2
- fibroblast activation
- Inhibitor
- inhibitor
- inhibit