Simtuzumab  (Synonyms: AB 0024; GS 6624)

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^{[1][2][3][4][5]}.

Human IgG4 kappa

Human IgG4 (S228P) kappa, Isotype Control

Human

LOXL2

Simtuzumab (1 µM; 15 days) reduces contraction heterogeneity, contraction time, diastolic time, and COL1A1 deposition area in LMNA^H222P 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.

Simtuzumab (5 mg/kg; i.p.; 3× weekly; 1 month) preserves left ventricular ejection fraction and fractional shortening, reduces myocardial fibrosis, and stabilizes left ventricular dilatation in a mouse model of LMNA-associated dilated cardiomyopathy^[1].
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.

4017  [NCBI]

Q9Y4K0

ELISA, FACS, Functional assay

Unconjugated

The product can be reconstituted/diluted with sterile PBS or saline.

145.5 kDa

1318075-13-6

Liquid

Colorless to light yellow

[Simtuzumab]

Shipping with dry ice.

Please refer to the lot-specific COA for specific buffer information.

Please store the product under the recommended conditions in the Certificate of Analysis.

• 
  Human IgG4 kappa

• 
  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.

• [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.

  [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.

  [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.

  [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.

  [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]