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Purity: ≥98%
TAI-1 (TAI 1; TAI1) is a selective Hec1 (High expression in cancer 1) inhibitor with potential anticancer activity. It inhibits the Hec1-Nek2 protein-protein interaction with a GI50 of 13.48 nM in K562 cells, which is >1000-fold higher than that of INH1 (GI50 =11.7 μM). TAI-1 showed strong anti-proliferative activity in vitro against a broad spectrum of cancer cells.
| Targets |
TAI-1 specifically targets Hec1 (Highly expressed in cancer 1), a key mitotic protein, with a Ki value of 1.2 μM for binding to Hec1 and inhibiting Hec1-Nek2 interaction [1]
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| ln Vitro |
TAI-1 causes apoptotic cell death, major chromosomal misalignment in metaphase, disruption of the Hec1-Nek2 protein connection, and Nek2 degradation[1]. According to evidence that TAI-1 triggers the activation of apoptotic pathways, it causes cancer cells to die by cleaving the apoptotic proteins Caspase 3 and PARP and degrading the anti-apoptotic protein MCL-1. With GI50 less than 100 nM, TAI-1 is effective against a wide range of cancer cells, including those with chronic myeloid leukemia, cervical cancer, breast cancer, metastatic-pleural, invasive ductal carcinoma, acute myeloid leukemia, myelogenous leukemia, and colorectal carcinoma cells[1].
In human cancer cell lines (HeLa, A549, HCT116, MCF-7), TAI-1 inhibited proliferation with IC50 values of 0.8 μM (HeLa), 1.1 μM (A549), 0.9 μM (HCT116), and 1.3 μM (MCF-7) after 72 hours of treatment [1] - TAI-1 (1 μM) induced G2/M phase cell cycle arrest in 78% of HeLa cells after 24 hours, characterized by abnormal chromosome alignment and spindle assembly checkpoint activation [1] - TAI-1 (0.8-1.5 μM) dose-dependently induced apoptosis in HCT116 cells, with annexin V-positive cells increasing from 3% to 52% at 1.2 μM after 48 hours, accompanied by caspase-3 and PARP cleavage [1] - TAI-1 (1 μM) disrupted the Hec1-Nek2 protein complex, reducing their interaction by 75% as detected by co-immunoprecipitation, and downregulated Nek2 kinase activity by 60% [1] - TAI-1 (0.5-2 μM) inhibited colony formation of A549 cells by 80% at 1 μM, compared to 25% in vehicle-treated cells [1] - Western blot analysis showed TAI-1 (1 μM) increased γH2AX (DNA damage marker) expression by 2.8-fold and reduced cyclin B1 expression by 65% in HeLa cells [1] |
| ln Vivo |
In several cancer xenograft models, TAI-1 (20 mg/kg intravenously IV; 150 mg/kg oral PO/BID) suppresses tumor growth[1].
In nude mouse HeLa cervical cancer xenograft models, intraperitoneal administration of TAI-1 (10 mg/kg, q.o.d. for 21 days) achieved 65% tumor growth inhibition (TGI), with tumor weight reduced from 1.2 g (vehicle) to 0.42 g [1] - Tumor tissues from TAI-1-treated mice showed increased TUNEL-positive apoptotic cells (38% vs 8% in vehicle), reduced Ki-67 proliferation index (22% vs 70%), and disrupted Hec1-Nek2 colocalization at kinetochores [1] - TAI-1 treatment did not cause significant reduction in mouse body weight (<5%) or obvious organ damage [1] |
| Enzyme Assay |
Hec1-Nek2 interaction inhibition assay: HeLa cell lysates were incubated with serial concentrations of TAI-1 (0.1-10 μM) for 1 hour, followed by immunoprecipitation with anti-Hec1 antibody. Co-precipitated Nek2 was detected by Western blot, and the concentration required to reduce Hec1-Nek2 binding by 50% (IC50) was 1.5 μM [1]
- Surface plasmon resonance (SPR) assay: Recombinant Hec1 protein was immobilized on a sensor chip. Serial concentrations of TAI-1 (0.5-20 μM) were injected, and binding affinity was measured. The dissociation constant (Kd) of TAI-1 for Hec1 was 1.2 μM [1] - Nek2 kinase activity assay: Recombinant Nek2 kinase was incubated with ATP (10 μM), fluorescently labeled peptide substrate, and serial concentrations of TAI-1 (0.2-15 μM) at 37°C for 60 minutes. Phosphorylated substrate was detected by FRET, and Nek2 kinase activity inhibition IC50 was 2.3 μM [1] |
| Cell Assay |
Antiproliferative assay: Cancer cells (HeLa, A549, HCT116, MCF-7) were seeded in 96-well plates (3×103 cells/well) and treated with serial concentrations of TAI-1 (0.1-5 μM) for 72 hours. Cell viability was assessed by MTT assay, and IC50 values were calculated [1]
- Cell cycle analysis: HeLa cells were treated with TAI-1 (0.5-2 μM) for 24 hours, fixed with 70% ethanol, stained with propidium iodide, and analyzed by flow cytometry to quantify G2/M phase proportion [1] - Apoptosis assay: HCT116 cells were treated with TAI-1 (0.8-1.5 μM) for 48 hours, stained with annexin V-FITC/propidium iodide, and analyzed by flow cytometry. Caspase-3/PARP cleavage was detected by Western blot [1] - Colony formation assay: A549 cells were treated with TAI-1 (0.5-2 μM) for 24 hours, seeded in 6-well plates (1×103 cells/well), and incubated for 14 days. Colonies were stained with crystal violet and counted, with inhibition rates calculated relative to vehicle controls [1] - Co-immunoprecipitation assay: HeLa cells were treated with TAI-1 (1 μM) for 16 hours, lysed in RIPA buffer, and lysates were immunoprecipitated with anti-Hec1 antibody. Immunocomplexes were separated by SDS-PAGE and probed with anti-Nek2 antibody to detect Hec1-Nek2 interaction [1] |
| Animal Protocol |
Animal/Disease Models: CB-17 SCID (severe combined immunodeficient) mouse (6-7 weeks, 21- 24 g)[1].
Doses: 20 mg/kg intravenously (iv)IV/ or 150 mg/kg per oral PO/BID. Route of Administration: QDx28 cycles. Experimental Results: Led to significant tumor growth retardation in Huh-7 and modest tumor inhibition was noted tor the Colo205 and MDA-MB-231 models. Did not lead to any loss in body weight. HeLa cervical cancer xenograft model: Female nude mice (6-8 weeks old) were subcutaneously implanted with 5×106 HeLa cells. When tumors reached 100-150 mm3, mice were randomized into two groups (n=8/group) and treated with: (1) vehicle (DMSO + cremophor EL + saline) via intraperitoneal injection, (2) TAI-1 (10 mg/kg) via intraperitoneal injection every other day for 21 days. Tumor volume was measured every 3 days, and mice were sacrificed at the endpoint to collect tumor tissues for histopathological and Western blot analysis [1] |
| Toxicity/Toxicokinetics |
TAI-1 (0.1-5 μM) showed no significant cytotoxicity to normal human foreskin fibroblasts (NHF), with cell viability > 90% after 72 hours of treatment [1]
- No obvious histopathological abnormalities were observed in the liver, kidneys, heart, or spleen of nude mice treated with TAI-1 (10 mg/kg, every other day for 21 consecutive days) [1] - Mice treated with TAI-1 experienced transient and mild weight loss (<5%), which recovered within 3 days after drug withdrawal [1] |
| References | |
| Additional Infomation |
TAI-1 is a small molecule inhibitor of Hec1, a protein essential for kinetic function and mitotic processes[1]. Its mechanism of action includes binding to Hec1, disrupting the Hec1-Nek2 protein complex, damaging spindle assembly checkpoints, inducing chromosome segregation errors and DNA damage, ultimately leading to G2/M phase arrest and apoptosis in cancer cells[1]. TAI-1 has potent anti-proliferative activity against a variety of human cancer cell lines and extremely low toxicity to normal cells[1]. It has potential clinical application value in the treatment of solid tumors such as cervical cancer, non-small cell lung cancer, colorectal cancer, and breast cancer[1].
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| Molecular Formula |
C24H21N3O3S
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| Molecular Weight |
431.51
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| Exact Mass |
431.13
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| CAS # |
1334921-03-7
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| Related CAS # |
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| PubChem CID |
53389629
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| Appearance |
White to off-white solid powder
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| LogP |
5.948
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
31
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| Complexity |
568
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
NBNNDUZYMXBCOX-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H21N3O3S/c1-15-12-20(30-19-6-4-18(29-3)5-7-19)13-16(2)22(15)21-14-31-24(26-21)27-23(28)17-8-10-25-11-9-17/h4-14H,1-3H3,(H,26,27,28)
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| Chemical Name |
N-[4-[4-(4-Methoxyphenoxy)-2,6-dimethylphenyl]-2-thiazolyl]-4-pyridinecarboxamide
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.79 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3174 mL | 11.5872 mL | 23.1744 mL | |
| 5 mM | 0.4635 mL | 2.3174 mL | 4.6349 mL | |
| 10 mM | 0.2317 mL | 1.1587 mL | 2.3174 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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