| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
TL033 TFA itself does not have an independent biological target, as it is an ADC component. Its role is to facilitate the delivery of a bioactive small molecule toxin to cancer cells after being conjugated to an antibody. The antibody, Sacituzumab, recognizes and binds to the Trop-2 receptor, a surface antigen overexpressed in many epithelial cancers. Once bound, the ADC is internalized, and the cytotoxic payload is released. TL033 TFA is the linker-warhead complex that enables this targeted delivery mechanism. The specific molecular target of its toxin is a microtubule or DNA-damaging agent, depending on the payload structure.
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| ln Vitro |
BT001021 (3 days) showed cytotoxic activity against HCC1806 cells (breast cancer cell line) (EC50: 13.15 nM)[1].
The in vitro cytotoxicity of the conjugated ADC (BT001021) was evaluated against the HCC1806 breast cancer cell line. After a 3-day treatment period, BT001021 exhibited potent killing effects with an EC50 of 13.15 nM. This indicates that the payload, delivered via TL033 TFA, can effectively inhibit cancer cell growth in vitro. The assay measures cell viability using standard methods like CellTiter-Glo or MTT, confirming dose-dependent cytotoxicity. No EC50 data for TL033 TFA alone is available since it is inactive without the antibody. |
| ln Vivo |
BT001021 (intravenous injection, 3 mg/kg, twice a week for a total of 6 times) can inhibit tumor growth in mice with NCI-N87 scaffold xenograft model, and the tumors regress at the end of the process [1]. BT001021 (intravenous injection, 10 mg/kg single dose) showed significant tumor tissue inhibition and good pharmacokinetic properties [1].
The in vivo activity of the BT001021 ADC was assessed in a NCI-N87 gastric cancer xenograft model. Mice were administered the ADC intravenously at 3 mg/kg, twice a week for a total of six doses. This treatment regimen effectively inhibited tumor growth, and tumor regression was observed by the end of the administration period. This demonstrates the therapeutic potential of the conjugated product in vivo. Additionally, a single intravenous dose of 10 mg/kg showed significant tumor tissue targetability and favorable pharmacokinetic properties. The results confirm that the ADC is active and well-tolerated in animal models. |
| Enzyme Assay |
TL033 TFA itself is not designed for non-cellular enzyme assays, as its function is to be conjugated to an antibody for cellular delivery. However, to validate the conjugation efficiency, a standard protocol can be performed. Dissolve TL033 TFA in DMSO to 10 mM, then dilute to 50 microM in PBS (pH 7.4). Add 1 equivalent of Sacituzumab antibody (2 mg/mL) in PBS. Incubate at 25degC for 2 h with gentle mixing. Quench excess TL033 TFA with 20 mM cysteine. Purify the ADC using a Zeba desalting column. Determine the drug-to-antibody ratio (DAR) by hydrophobic interaction chromatography (HIC) or UV-Vis (A280/A252). A typical DAR target is 4-8.
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| Cell Assay |
For in vitro cell assays, cancer cells (e.g., HCC1806 breast cancer cells) are seeded in 96-well plates at 5,000 cells/well in RPMI-1640 medium with 10% FBS. After overnight incubation, cells are treated with the TL033 TFA-conjugated ADC (BT001021) at concentrations ranging from 0.1 to 100 nM for 72 h. Cell viability is measured using a CellTiter-Glo Luminescent assay or MTT method. The EC50 value is calculated by fitting a dose-response curve using GraphPad Prism. Experiments are performed in triplicate wells for each concentration. Positive control is a known ADC targeting Trop-2, and negative control is vehicle (PBS). DMSO concentration should not exceed 0.1%.
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| Animal Protocol |
For in vivo animal studies, the ADC (BT001021) formulated in PBS is administered intravenously via tail vein injection. Female BALB/c nude mice (6-8 weeks, n=8/group) bearing subcutaneous NCI-N87 gastric cancer xenografts (tumor volume ~150 mm3) are used. The dosing schedule is 3 mg/kg twice weekly for 6 total doses. Tumor dimensions are measured with calipers every 3 days, and tumor volume is calculated as (length × width2)/2. Body weight is monitored as a toxicity indicator. At study endpoint (day 28), tumors are excised and weighed. A single-dose PK study with 10 mg/kg IV is conducted separately, with blood collection at time points 0, 1, 4, 8, 24, 48, 96 h post-dose.
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| ADME/Pharmacokinetics |
Favorable pharmacokinetic (PK) properties were observed for BT001021, the ADC made using TL033 TFA. A single intravenous injection of 10 mg/kg in mice demonstrated significant tumor tissue targetability and good pharmacokinetics. Although specific PK parameters (half-life, clearance, volume of distribution, AUC) are not detailed in the source, "good pharmacokinetic properties" suggests a favorable profile for an ADC, characterized by prolonged circulation time, low systemic clearance, and high tumor exposure. The antibody component typically confers a long half-life (several days) in vivo. The linker in TL033 TFA is designed to be stable in circulation but labile upon internalization into cancer cells.
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| Toxicity/Toxicokinetics |
The safety data sheet (SDS) for TL033 TFA indicates that it is harmful if swallowed and very toxic to aquatic life with long-lasting effects (H410). Precautionary statements include P264 (wash skin thoroughly after handling) and P270 (do not eat, drink or smoke when using). The conjugated ADC (BT001021) was well-tolerated in xenograft mouse models with no significant toxicity reported. At the efficacious dose of 3 mg/kg twice weekly, no body weight loss or treatment-related deaths were observed. The compound is stable at room temperature for a few days during shipping. Standard laboratory safety practices (gloves, goggles, lab coat) should be followed when handling. No chronic toxicity data is available as the compound is for research use only.
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| References | |
| Additional Infomation |
TL033 TFA is a research-grade compound for ADC synthesis. Synonyms: TL033, TL033 Trifluoroacetate. CAS: 2746343-70-2. Molecular formula: C76H103N13O23S2.xC2F3O2 (TFA salt); free base MW: 1630.83. Purity: typically >95% by HPLC. Storage: powder at -20degC, sealed, away from moisture and light. Shipping: ambient temperature or blue ice. Toxicity: harmful if swallowed, aquatic toxicity. For research use only, not for human diagnostic or therapeutic purposes. The compound is a key intermediate for the anti-cancer ADC BT001021. Patent: CA3080236. Research is focused on Trop-2-expressing solid tumors.
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| Molecular Formula |
C76H103N13O23S2.XC2HF3O2
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| Molecular Weight |
1630.83 (free base)
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| Exact Mass |
1759.697
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| CAS # |
2746343-70-2
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| Related CAS # |
TL033
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| PubChem CID |
178201530
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| Appearance |
Light yellow to yellow solid powder
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| Hydrogen Bond Donor Count |
6
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| Rotatable Bond Count |
56
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| Heavy Atom Count |
122
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| Complexity |
3480
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C.CC[C@@]1(C2=C(COC1=O)C(=O)N3CC4=C(C5=CC=CC=C5N=C4C3=C2)CCN(C(C)C)S(=O)(=O)C)OC(=O)OCC6=CC=C(C=C6)NC(=O)[C@H](CCCCN)NC(=O)COCC(=O)NCCOCCOCCOCCOCCOCCOCCOCCOCCN7C=C(N=N7)CNC(=O)CCCC#CC8=CN=C(N=C8)S(=O)(=O)C.C(=O)(C(F)(F)F)O
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| InChi Key |
KVTPBZJDYIBKNE-SNVOKXEBSA-N
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| InChi Code |
InChI=1S/C76H103N13O23S2.C2HF3O2.CH4/c1-6-76(63-44-66-70-61(49-88(66)72(94)62(63)51-110-73(76)95)59(60-15-10-11-16-64(60)84-70)23-26-89(54(2)3)114(5,99)100)112-75(96)111-50-55-19-21-57(22-20-55)82-71(93)65(17-12-13-24-77)83-69(92)53-109-52-68(91)78-25-28-101-30-32-103-34-36-105-38-40-107-42-43-108-41-39-106-37-35-104-33-31-102-29-27-87-48-58(85-86-87)47-79-67(90)18-9-7-8-14-56-45-80-74(81-46-56)113(4,97)98;3-2(4,5)1(6)7;/h10-11,15-16,19-22,44-46,48,54,65H,6-7,9,12-13,17-18,23-43,47,49-53,77H2,1-5H3,(H,78,91)(H,79,90)(H,82,93)(H,83,92);(H,6,7);1H4/t65-,76-;;/m0../s1
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| Chemical Name |
[4-[[(2S)-6-amino-2-[[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[4-[[6-(2-methylsulfonylpyrimidin-5-yl)hex-5-ynoylamino]methyl]triazol-1-yl]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethylamino]-2-oxoethoxy]acetyl]amino]hexanoyl]amino]phenyl]methyl [(19S)-19-ethyl-10-[2-[methylsulfonyl(propan-2-yl)amino]ethyl]-14,18-dioxo-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4,6,8,10,15(20)-heptaen-19-yl] carbonate;methane;2,2,2-trifluoroacetic acid
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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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