| Field | Specification |
|---|---|
| CAS no. | |
| Applications | |
| Molecular weight | |
| Molecular formula | C19H22N6S |
| Purity | |
| SMILES | |
| Form | Solid |
| Storage | |
| Shipping | |
| Catalog no. (Mfr.) | |
| Main SKU |
Compound Overview
COTI-2, an anti-cancer agent with low toxicity, is an orally available, third-generation activator of mutant forms of p53. It works both by reactivating mutant p53 and by inhibiting the PI3K/AKT/mTOR pathway, and it induces apoptosis in multiple human tumor cell lines. COTI-2 shows antitumor activity in HNSCC through both p53-dependent and p53-independent mechanisms, and it converts mutant p53 to a wild-type conformation[1][2][3]. It is supplied as a light yellow to yellow solid (C19H22N6S, MW 366.48) at 99.02% purity.
Physical & Chemical Properties
| CAS Number | 1039455-84-9 |
|---|---|
| Molecular Formula | C19H22N6S |
| Molecular Weight | 366.48 g/mol |
| Purity | 99.02% |
| Appearance | Solid |
| Color | Light yellow to yellow |
| SMILES | S=C(N1CCN(C2=NC=CC=C2)CC1)N/N=C3CCCC4=C\3N=CC=C4 |
| Signaling Pathway | Apoptosis |
| Solubility | In Vitro: DMSO: 5 mg/mL (13.64 mM; Requires sonication; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO) |
| Storage | Powder: -20°C, 3 years; 4°C, 2 years. In solvent: -80°C, 2 years; -20°C, 1 year. |
| Shipping | Room temperature in continental US; may vary elsewhere. |
Literature Cited
Sources cited in this description and in the In Vitro & In Vivo Data tab. Peer-reviewed publications that used this product are listed under References.
[1]. Duffy MJ, et al. Mutant p53 as a target for cancer treatment. Eur J Cancer. 2017 Sep;83:258-265.
Safety
For Research Use Only. Not for use in diagnostic or therapeutic procedures, and not for human or veterinary use. Handle in accordance with the Safety Data Sheet and your institution's chemical hygiene plan.
In Vitro
| Solvent | Solubility | Notes |
|---|---|---|
| DMSO | 5 mg/mL (13.64 mM) | requires sonication; use freshly opened DMSO (absorbed moisture lowers solubility) |
Aliquot the stock solution and store it at -80°C (up to 2 years) or -20°C (up to 1 year); avoid repeated freeze-thaw cycles.
In Vivo
Choose the formulation that suits the animal model and route of administration; percentages are volume ratios of the final working solution. Start from a clear DMSO stock (see In Vitro above), add the co-solvents one at a time in the order listed, mixing after each addition, and prepare the working solution fresh on the day of dosing. If precipitation or phase separation occurs, gentle warming or sonication can help.
Protocol 1
| Composition | 10% DMSO + 90% Corn Oil |
|---|---|
| Result | ≥ 0.67 mg/mL (1.83 mM); clear solution |
| How to prepare | Gives a clear solution at ≥ 0.67 mg/mL (saturation not determined). Use with caution if continuous dosing will exceed two weeks. For 1 mL of working solution: add 100 μL DMSO stock (6.7 mg/mL) to 900 μL corn oil. |
Direct preparation of the working solution
These formulations are prepared directly, without a DMSO stock; use them promptly after preparation.
Protocol 2
| Composition | 50% PEG300 + 50% saline |
|---|---|
| Result | 5 mg/mL (13.64 mM); suspension; requires sonication |
Protocol 3
| Composition | 15% Cremophor EL + 85% saline |
|---|---|
| Result | 5 mg/mL (13.64 mM); suspension; requires sonication |
Data provided by the manufacturer.
In Vitro
Following 72 h of treatment, COTI-2 efficiently inhibits the proliferation rate of all tested cell lines. Tumor cell proliferation is significantly inhibited by COTI-2 in all three cell lines (COLO-205, HCT-15, and SW620). COTI-2 is active against every human glioblastoma cell line tested (U87-MG, SNB-19, SF-268, and SF-295) at relatively low concentrations. In SHP-77 cells, COTI-2 treatment at approximate IC50 concentrations induces early apoptosis in 40 to 47% of total cells[2].
In Vivo
COTI-2 significantly inhibits tumor growth in HT-29 human colorectal tumor xenografts at a dose of 10 mg/kg. Besides reducing tumor volumes at specific times post-treatment, COTI-2 delays the time needed for tumors to reach specified volumes. In the SHP-77 SCLC xenograft model, COTI-2 also significantly inhibits tumor growth at a dose as low as 3 mg/kg. In nude mice, COTI-2 treatment lowers U87-MG tumor volumes at set times post-treatment, and it extends the time U87-MG xenografts need to grow. Control tumors in vehicle-treated mice need only 5 days to reach an average volume of 828 mm3, whereas tumors in COTI-2-treated animals need twice as long (10 days) to reach a similar mean volume (857 mm3). OVCAR-3 xenograft growth is effectively inhibited by COTI-2 treatment regardless of the route of administration[2].
Data provided by the manufacturer. Numbered citations refer to the Literature Cited list in the product description.
Kinase Assay[2]
Use the AMBIT BIOSCIENCES KINOMESCAN assay to test the interaction of COTI-2 with 227 kinases. Incubate streptavidin-coated magnetic beads at 25°C for 30 min with biotinylated small molecule ligands, producing affinity resins for kinase assays. Block the liganded beads with excess biotin, then wash them with blocking buffer (1% BSA, 0.05% Tween 20, 1 mM DTT), which removes unbound ligand and lowers non-specific binding. Assemble binding reactions in 1× binding buffer (20% SeaBlock, 0.17× PBS, 0.05% Tween 20, 6 mM DTT), combining phage lysates with liganded affinity beads and COTI-2. Carry out all reactions in polystyrene 96-well plates pre-treated with blocking buffer, in a final volume of 0.1 mL[2].
Cell Assay[2]
Culture SHP-77 cells with various concentrations of COTI-2 for 48 h. Wash the cells twice with 1× cold PBS and stain with Annexin V and 7AAD according to the manufacturer's instructions. Briefly, add 5 μL of Annexin V and 7AAD to 1×105 cells and incubate for 15 min at room temperature in the dark. Then add 400 μL of 1× binding buffer to the cells, composed of 100 mM HEPES, pH 7.4, 140 mM NaCl, and 2.5 mM CaCl2. Finally, analyze the cells using a flow cytometer[2].
Animal Administration[2]
Inject SHP-77 and HT-29 cells in 50% matrigel into the flanks of NCr-nu mice (2×106 cells per injection site; n=5 mice per group). For SHP-77 xenografts, start COTI-2 treatment before palpable tumors appear: one day after SHP-77 cell injection, dose animals with COTI-2 at 3 mg/kg once every two days for up to 38 days. Estimate tumor sizes at 5, 10, 17, 24, and 38 days by standard caliper measurements. For HT-29 xenografts, assess the capacity of COTI-2 to suppress growth of established tumors: let HT-29 xenografts reach 200 mm3 before beginning IP treatment, either COTI-2 (10 mg/kg, 5 days per week for 7 weeks) or saline IP. Measure tumor growth every 4 days by caliper measurement[2].
Data provided by the manufacturer. Numbered citations refer to the Literature Cited list in the product description.
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A cytosolic mutp53(E285K) variant confers chemoresistance of malignant melanoma. Cell Death Dis 2023 Dec 14;14(12):831. PMID: 38097548
Repurposing antiparasitic antimonials to noncovalently rescue temperature-sensitive p53 mutations. Cell Rep 2022 Apr 12;39(2):110622. PMID: 35417717
Improving Reporter Gene Assay Methodology for Evaluating the Ability of Compounds to Restore P53 Activity. Int J Mol Sci 2022 Nov 10;23(22):13867. PMID: 36430341
COTI-2 suppresses the malignancy of bladder cancer by inducing apoptosis via the AMPK-mTOR signaling pathway. Iran J Basic Med Sci 2025;28(3):240-246. PMID: 39906622
