| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Other Sizes |
| Targets |
TD-52 targets CIP2A (cancerous inhibitor of protein phosphatase 2A), an oncoprotein that inhibits PP2A activity and stabilizes c-Myc, promoting cancer cell proliferation and survival. By inhibiting CIP2A, TD-52 restores PP2A activity, which dephosphorylates and destabilizes oncogenic proteins. TD-52 regulates the CIP2A/PP2A/p-Akt signaling pathway and mediates apoptotic effects in cancer cells. It has less p-EGFR inhibition than erlotinib.
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| ln Vitro |
TD52 (2-10 μM; 48 hours) exhibits an anti-proliferative effect and causes varying levels of apoptosis in these cell lines[1].
TD52 (5 μM; 48 hours) has minimal effects on p-EGFR or EGFR expression but downregulated CIP2A expression[1]. TD52 (2.5, 5, 7.5 μM; 48 hours) time-dependently induces apoptosis while also downregulating CIP2A and p-Akt[1]. TD52 (5 μM; 24 hours)significantly boosts PP2A's phosphatase activity in TNBC cells[1]. TD52 (5 μM; 48 hours) has no obvious effects on other common RTKs, such as IGFR, PDGFR and VEGFR2[1]. In vitro, TD-52 induces apoptosis through downregulation of CIP2A in HCC, NSCLC, and TNBC cells. It shows potent antitumor efficacy with IC50 values of 0.9, 0.9, 0.8, and 1.2 μM in HA22T, Hep3B, PLC5, and Sk-Hep1 cell lines, respectively. TD-52 regulates the CIP2A/PP2A/p-Akt signaling pathway and mediates apoptotic effects in triple-negative breast cancer (TNBC) cells. It has less p-EGFR inhibition than erlotinib. |
| ln Vivo |
TD52 (10 mg/kg/day; oral gavage; for 52 days) significantly reduces MDA-MB-468 xenograft tumor size and tumor weight[1].
In vivo, TD-52 is orally active and has potent antitumor efficacy on HCC and TNBC cells. By inhibiting CIP2A, the compound induces apoptosis and suppresses tumor growth. However, specific in vivo efficacy data and dosing details have not been extensively detailed in the available literature. Further preclinical studies would be required. |
| Enzyme Assay |
For in vitro binding and activity assays, recombinant CIP2A or PP2A proteins are used to assess compound binding and activity. The test compound is added at various concentrations (0.1-100 µM). CIP2A inhibition is measured by assessing PP2A activity or by measuring downstream signaling such as p-AKT levels.
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| Cell Assay |
For cell proliferation assays, cancer cell lines (such as HCC, NSCLC, or TNBC cell lines) are seeded in 96-well plates and treated with TD-52 at concentrations ranging from 0.1-100 µM for 72 hours. Cell viability is assessed using MTT or CellTiter-Glo assays. IC50 values are calculated from dose-response curves. Apoptosis is assessed by measuring caspase activity or by Annexin V staining.
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| Animal Protocol |
For in vivo efficacy studies, immunodeficient mice would be implanted with HCC or TNBC xenografts. When tumors reach a predetermined size, mice would be randomized and treated with TD-52 via oral gavage at doses determined from pharmacokinetic studies. Tumor volumes would be measured twice weekly. At study endpoint, tumors would be collected for analysis of CIP2A, PP2A, and p-AKT levels.
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| ADME/Pharmacokinetics |
TD-52 is orally active. It is soluble in DMSO. Storage is recommended at -20°C for long-term stability. Further detailed PK parameters including half-life, oral bioavailability, and tissue distribution would be required for in vivo studies. The compound is for research use only and is not intended for human or veterinary use.
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| Toxicity/Toxicokinetics |
Toxicological data for TD-52 have not been extensively reported. As a research compound, it is intended for laboratory use only and is not for human or veterinary use. Standard safety precautions should be followed when handling this compound. Comprehensive toxicology studies would be required before any clinical development.
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| References | |
| Additional Infomation |
TD-52 is an erlotinib derivative and an orally active CIP2A inhibitor. It induces apoptosis through downregulation of CIP2A in HCC, NSCLC, and TNBC cells. TD-52 regulates the CIP2A/PP2A/p-Akt signaling pathway. It is a research tool and is not approved for clinical use.
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| Molecular Formula |
C24H16N4
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|---|---|
| Molecular Weight |
360.41064453125
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| Exact Mass |
360.137
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| Elemental Analysis |
C, 79.98; H, 4.47; N, 15.55
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| CAS # |
1798328-24-1
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| Related CAS # |
TD52 dihydrochloride
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| PubChem CID |
118656842
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| Appearance |
White to yellow solid
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| LogP |
5.5
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
28
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| Complexity |
559
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C#CC1=CC(=CC=C1)NC2=NC3=CC=CC=C3N=C2NC4=CC=CC(=C4)C#C
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| InChi Key |
SCUPZFSEJFWQIS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H16N4/c1-3-17-9-7-11-19(15-17)25-23-24(26-20-12-8-10-18(4-2)16-20)28-22-14-6-5-13-21(22)27-23/h1-2,5-16H,(H,25,27)(H,26,28)
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| Chemical Name |
2-N,3-N-bis(3-ethynylphenyl)quinoxaline-2,3-diamine
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| Synonyms |
TD52; TD 52; TD-52; erlotinib analogue; erlotinib derivative
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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) |
DMSO: ~100 mg/mL (~277.5 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (6.94 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (6.94 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7746 mL | 13.8731 mL | 27.7462 mL | |
| 5 mM | 0.5549 mL | 2.7746 mL | 5.5492 mL | |
| 10 mM | 0.2775 mL | 1.3873 mL | 2.7746 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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