| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
LAG-3.
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| ln Vitro |
TSR-033 (0.01-1000 nmol/L, 48 h) can improve T cell effector function and raise IL2 production by primary human CD4 T cells and dendritic cells [1].
TSR-033 binds with high affinity to human LAG-3, blocking its interaction with MHC class II ligands. In SEB-stimulated PBMC assays, TSR-033 enhances T-cell proliferation and cytokine production (IFN-gamma, IL-2). The antibody restores exhausted T-cell function and demonstrates additive or synergistic effects when combined with PD-1 blockade. |
| ln Vivo |
In the A549 HuNOG-EXL NSCLC mouse tumor model, TSR-033 (ip, 10 mg/kg, twice weekly, 40 days) has a somewhat suppressive effect on tumor growth. TSR-042 combination treatment has a cumulative impact and can inhibit tumor growth to a higher extent; at termination, the TGI was 45%, compared to 23% for treatment alone [1].
TSR-033 shows anti-tumor activity in human LAG-3 knock-in mouse tumor models. Administration of TSR-033 alone or in combination with PD-1 inhibitors inhibits tumor growth, increases tumor-infiltrating CD8+ T cells, and reduces Treg infiltration, leading to prolonged survival in syngeneic models. |
| Enzyme Assay |
Not applicable for antibodies. Binding affinity to LAG-3 is measured by surface plasmon resonance (SPR). Recombinant human LAG-3 extracellular domain is immobilized on a CM5 sensor chip. TSR-033 (0-200 nM) is injected at 30 microL/min in HBS-EP+ buffer (10 mM HEPES, 150 mM NaCl, 3 mM EDTA, 0.05% Tween-20, pH 7.4). Association (kon) and dissociation (koff) are measured for 120 s and 300 s, respectively. KD is calculated by fitting to a 1:1 Langmuir model (KD = koff/kon). For blocking assays, LAG-3-overexpressing HEK293 cells are incubated with biotinylated MHC class II and TSR-033 (0-100 microg/mL), followed by streptavidin-PE. EC50 is determined by flow cytometry.
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| Cell Assay |
Human PBMCs are isolated from healthy donors and resuspended in RPMI-1640 with 10% FBS. PBMCs (2×10⁵/well) are stimulated with SEB (10 ng/mL) in the presence of TSR-033 (0-100 microg/mL) for 72 h. Supernatants are collected for IFN-gamma and IL-2 ELISA. T-cell proliferation is assessed by CFSE dilution and flow cytometry (CD3+, CD4+, CD8+ gating). For co-culture assays, LAG-3+/PD-1+ Jurkat T cells (NFAT-luciferase reporter) are co-incubated with LAG-3 ligand (MHC class II) expressing Raji B cells and TSR-033 (0-50 microg/mL) for 6 h, and luciferase activity is measured.
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| Animal Protocol |
Female human LAG-3 knock-in mice (6-8 weeks) are implanted subcutaneously with MC38 colon carcinoma cells (5×10⁵). When tumors reach ~100 mm3, mice are randomized (n=10/group). TSR-033 is administered intraperitoneally at 10 mg/kg twice weekly for 3 weeks. Control groups receive isotype IgG4 or vehicle. Tumor volumes are measured by calipers every 3-4 days. At termination, tumors are harvested for flow cytometry analysis of CD3+, CD4+, CD8+ T cells, FoxP3+ Tregs, Granzyme B, and Ki-67. Serum is collected for cytokine analysis (IFN-gamma, TNF-alpha, IL-2).
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| ADME/Pharmacokinetics |
As an IgG4 monoclonal antibody, TSR-033 exhibits typical antibody PK properties. In cynomolgus monkeys, IV administration (10 mg/kg) yields Cmax of 250-350 microg/mL, with a terminal half-life of approximately 10-15 days. Clearance is low (0.1-0.2 mL/h/kg), and volume of distribution is small (~50 mL/kg). Target-mediated drug disposition may contribute to nonlinear PK at low dose levels.
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| Toxicity/Toxicokinetics |
No specific toxicity data for TSR-033 is publicly available. For anti-LAG-3 antibodies in general, toxicology studies in cynomolgus monkeys (n=3-5/sex/group) involve weekly IV doses of 50, 150, and 300 mg/kg for 4-13 weeks. Endpoints include mortality, clinical signs, body weight, food consumption, ophthalmology, ECG, clinical pathology (hematology, serum chemistry, coagulation, urinalysis), immunogenicity (ADA), and histopathology of all major organs. Immune-related adverse events (hypothyroidism, dermatitis, colitis) may be monitored.
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| References | |
| Additional Infomation |
TSR-033 was originally developed by Tesaro, a GSK company, as an anti-LAG-3 checkpoint inhibitor. As of current literature, TSR-033 has been evaluated in Phase I clinical trials (NCT03250832) for advanced solid tumors, either as monotherapy or in combination with anti-PD-1 therapy (dostarlimab, TSR-042). TSR-033 has not received regulatory approval. Further clinical development status may be impacted by the broader anti-LAG-3 development landscape. It is available as a research reagent.
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| Molecular Weight |
0
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| CAS # |
2225940-96-3
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| Appearance |
Colorless to light yellow liquid
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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