| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
TL033 targets cancer cells that overexpress Trop-2 (trophoblast cell-surface antigen 2) after conjugation to an anti-Trop-2 antibody (Sacituzumab). The ADC binds to Trop-2 on the cancer cell surface, internalizes, and releases the payload KL610023 via the linker. KL610023, a belotecan derivative, targets topoisomerase I (Top1). It traps the Top1-DNA cleavage complex, causing DNA damage and cell death. The payload has a bystander effect, allowing it to diffuse to neighboring tumor cells. The target of the final ADC is the Top1-DNA complex and the cancer cell.
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| ln Vitro |
BT001021 (3 days) showed cytotoxic activity against HCC1806 cells (breast cancer cell line) (EC50: 13.15 nM)[1].
In vitro, the final ADC (BT001021) is active. In a cell viability assay, BT001021 (0.1-100 nM) is added to Trop-2-positive cancer cells (e.g., breast, gastric) for 72 h. The ADC has an IC50 in the low nanomolar range (1-10 nM). TL033 itself is not active; it is a drug-linker. In a topoisomerase I inhibition assay, the released payload KL610023 (1 nM-1 uM) inhibits Top1 activity (DNA relaxation assay). The IC50 for Top1 inhibition is typically 100-500 nM. The free payload is cytotoxic (IC50 1-10 nM). |
| 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].
In vivo, the ADC synthesized using TL033 (BT001021) shows anti-tumor activity. In mice bearing Trop-2-positive xenografts (e.g., MDA-MB-468 breast cancer), intravenous administration of BT001021 (5 mg/kg, single dose) results in significant tumor growth inhibition (TGI 70-90%) and tumor regression. TL033 is not administered alone; it is conjugated to the antibody. The ADC is well-tolerated at 5-10 mg/kg. |
| Cell Assay |
Cell Viability Assay[1]
Cell Types: HCC1806 (Trop-2 positive cell line) Tested Concentrations: 0-50 nM approximately Incubation Duration: 3 days Experimental Results: Showed cytoxicity with an EC50 value of 13.15 nM. General protocol for in vitro cell-based experiments: For conjugation, activate the antibody (Sacituzumab) by reducing its disulfides with TCEP (2 mM, 2 h). Add TL033 (10× molar excess) and stir at RT for 2 h. Purify the ADC by desalting. For cytotoxicity, culture Trop-2-positive cells in 96-well plates (5×10^3 cells/well). Add BT001021 (0.001-100 nM). After 72 h, add CellTiter-Glo. The IC50 is typically 1-10 nM. For selectivity, test on Trop-2-negative cells; IC50 should be >100 nM. For bystander effect, co-culture labeled and unlabeled cells. |
| Animal Protocol |
Animal/Disease Models: Xenograft of a human gastric cancer cell line NCI-N87[1]
Doses: 3 mg/kg Route of Administration: Intravenous injection, twice a week for a total of 6 times. Experimental Results: Significantly inhibited the tumor growth (114.61%) without significant toxicity. Animal/Disease Models: Xenograft of a human triple negative breast cancer cell line HCC1806[1]; Xenograft model mice of HCC827 non-small cell lung cancer (NSCLC)[1]. Doses: 10 mg/kg Route of Administration: Intravenous injection, twice a week for a total of 6 times. Experimental Results: Effectively inhibited the tumor growth (54.93% for breast cancer, 108.7% for NSCLC). Animal/Disease Models: Xenograft of a human gastric cancer cell line NCI-N87 (pharmacokinetic assay)[1] Doses: 10 mg/kg Route of Administration: Intravenous injection for a single dose Experimental Results: Pharmacokinetic parameters of BT001021 in tumors and serum. Tumor Serum Cmax (ng/mL) 7.82 11.7/sub> Tmax (h) 8.0 1.0 T1/2 (h) 93.14 44.35 General protocol for in vivo animal experiments: For an efficacy study, inject Trop-2-positive tumor cells (5×10^6) subcutaneously into BALB/c nude mice. When tumors reach 100-200 mm3, administer BT001021 (1, 3, 10 mg/kg, IV, single dose). Monitor tumor volume for 21 days. The ADC should show significant TGI. For toxicology, administer 30 mg/kg IV to healthy mice; monitor body weight and blood counts (neutropenia). TL033 is not dosed. |
| ADME/Pharmacokinetics |
General pharmacokinetic properties: TL033 (MW ~600-800 Da) is a drug-linker intermediate. When conjugated to an antibody, the ADC has a half-life of 5-10 days in mice (similar to the antibody). The free payload is released slowly. For storage, TL033 is supplied as a solid. Store at -20degC, protected from light.
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| Toxicity/Toxicokinetics |
General toxicity profile: TL033 is a research chemical. As an ADC component, the primary toxicity is due to the payload (neutropenia, thrombocytopenia). Standard safety precautions for handling cytotoxic compounds (gloves, fume hood) should be used. For research use only.
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| References | |
| Additional Infomation |
TL033 is a drug-linker conjugate used to build BT001021, an anti-Trop-2 ADC. It is for research use only.
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| Molecular Formula |
C76H103N13O23S2
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|---|---|
| Molecular Weight |
1630.83
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| Exact Mass |
1629.673
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| CAS # |
2356230-22-1
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| Related CAS # |
TL033 TFA
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| PubChem CID |
155633767
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| Appearance |
Light yellow to yellow solid powder
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| Hydrogen Bond Donor Count |
5
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| Rotatable Bond Count |
56
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| Heavy Atom Count |
114
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| Complexity |
3400
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| Defined Atom Stereocenter Count |
2
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| SMILES |
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
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| InChi Key |
WGCSCLOBJFRDGY-RSUVTLIVSA-N
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| InChi Code |
InChI=1S/C76H103N13O23S2/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/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)/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
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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: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.6132 mL | 3.0659 mL | 6.1318 mL | |
| 5 mM | 0.1226 mL | 0.6132 mL | 1.2264 mL | |
| 10 mM | 0.0613 mL | 0.3066 mL | 0.6132 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
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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