COTI-2 hydrochloride
Based on 4 publication(s) in Google Scholar
COTI-2 hydrochloride is an orally active thiosemicarbazone anticancer agent and p53 mutant activator. COTI-2 hydrochloride induces Apoptosis. COTI-2 hydrochloride triggers the activation of AMPK and the inhibition of the mTOR pathway. COTI-2 hydrochloride induces DNA damage and replication stress responses. COTI-2 hydrochloride binds to misfolded mutant p53 proteins, thereby inducing conformational changes that restore p53 to its normal state and reactivate its function. COTI-2 hydrochloride acts on a variety of cancer cell lines and xenografts. COTI-2 hydrochloride can be used in research related to colorectal cancer, small cell lung cancer, glioblastoma, breast cancer, and ovarian cancer.
For research use only. We do not sell to patients.
- CAS No.: 1204956-74-0
- Formula: C19H23ClN6S
- Molecular Weight:402.94
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Publications Citing Use of MedChemExpress (MCE) COTI-2 hydrochloride
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Biological Activity
Description
In Vitro
COTI-2 (72 h treatment) hydrochloride inhibits the proliferation of all tested cancer cell lines, including HEC-1A, Ovcar-8, KLE, HL-60, A549 and H226, with IC50 values ranging from near 0 nM to over 200 nM after 72 h of treatment[1].
COTI-2 (96 h treatment) hydrochloride potently inhibits the proliferation of colorectal cancer cell lines SW620, COLO-205 and HCT-15, as well as non-small cell lung cancer (NSCLC) cell lines H292 and H1975, and exhibits superior efficacy to Cetuximab (HY-P9905) or Erlotinib (HY-50896) after 96 h of treatment[1].
COTI-2 (4-7 days) hydrochloride inhibits the proliferation of U87-MG, SNB-19, SF-268 and SF-295 glioblastoma cell lines, with IC50 values in the nanomolar range; after 4-7 days of treatment, its potency against U87-MG and SNB-19 cell lines is 10 to 500-fold that of Cisplatin (HY-17394) and BCNU (HY-13585)[1].
COTI-2 (100-1000 nM; 48 h) hydrochloride induces apoptosis in small cell lung cancer SHP-77 cells. Specifically, treatment with IC50 concentrations (100 nM, 250 nM) for 48 h results in early apoptosis in 40.13% to 46.68% of cells, while treatment with the IC90 concentration (1000 nM) for 48 h induces early apoptosis as well as late apoptosis/necrosis in most cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:Diverse human cancer cell lines including small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), colorectal, glioma/astrocytoma, ovarian carcinoma, breast, leukemia, endometrial, and pancreatic cancer cell lines (HEC-1A, Ovcar-8, KLE, HL-60, A549, H226)
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Concentration:Multiple concentrations
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Incubation Time:72 h
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Result:Efficiently inhibited the proliferation rate of all tested cell lines.
Showed nanomolar sensitivity in most cell lines, with IC50 values ranging from near 0 nM to over 200 nM.
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Cell Line:Human glioblastoma cell lines (U87-MG, SNB-19, SF-268, SF-295)
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Concentration:Multiple concentrations
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Incubation Time:4-7 days
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Result:Was active against all tested glioblastoma cell lines at relatively low concentrations.
Showed superior activity and lower nanomolar IC50 values compared to cisplatin and BCNU in U87-MG and SNB-19 cell lines, being 10 to 500 times more effective than these agents.
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Cell Line:SHP-77 human small cell lung cancer (SCLC) cells
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Concentration:100 nM, 250 nM, 1000 nM
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Incubation Time:48 h
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Result:Induced early apoptosis in 40.13% to 46.68% of total cells at IC50 concentrations (100 nM, 250 nM).
Induced early apoptosis in 17.15% and late apoptosis/necrosis in 19.25% of total cells, with 13.64% of cells undergoing necrosis, at IC90 concentration (1000 nM).
In Vivo
COTI-2 (3 mg/kg; i.p.; once every two days; up to 38 days) hydrochloride effectively inhibits the growth of SHP-77 small cell lung cancer xenografts, and exhibits superior efficacy compared with standard chemotherapy compounds[1].
COTI-2 (8 mg/kg; intraperitoneal injection; three times per week) hydrochloride doubles the time required for U87-MG glioblastoma xenografts to reach the target tumor volume, and significantly delays tumor growth[1].
COTI-2 (200 mg/kg; p.o.; 5 days per week) hydrochloride significantly inhibits the growth of MDA-MB-231 breast cancer xenografts[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NCr-nu mice (immunocompromised, n=5 per group)[1]
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Dosage:10 mg/kg
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Administration:i.p.; 5 days a week; 7 weeks
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Result:Significantly reduced tumor volumes at multiple time points post-treatment.
Increased the time for tumors to reach a mean volume of ~620 mm3 from 32 days to 48 days, a 50% increase compared to controls.
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Animal Model:NCr-nu mice (immunocompromised, n=5 per group)[1]
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Dosage:3 mg/kg
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Administration:i.p.; once every two days; up to 38 days
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Result:Significantly inhibited SHP-77 xenograft growth to a greater degree than cisplatin or paclitaxel.
Maintained treated tumors at a minimal volume (~10 mm3 or less) through 38 days, while control tumors reached ~260 mm3.
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Animal Model:Nude mice (immunocompromised, 7 mice per group)[1]
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Dosage:8 mg/kg
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Administration:i.p.; 3 times per week
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Result:Significantly reduced tumor volumes at multiple time points.
Doubled the time for tumors to reach a mean volume of ~840 mm3 from 5 days to 10 days compared to controls.
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Animal Model:SCID mice (immunocompromised, 7 mice per group, 6-8 weeks old)[1]
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Dosage:200 mg/kg
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Administration:p.o.; 5 days per week
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Result:Significantly delayed MDA-MB-231 xenograft growth compared to vehicle controls.
Chemical Information
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CAS No. 1204956-74-0
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Molecular Weight 402.94
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Formula C19H23ClN6S
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SMILES
S=C(N1CCN(CC1)C2=NC=CC=C2)N/N=C3C4=NC=CC=C4CCC/3.Cl
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Publications (4)
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Journal Impact Factor
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Most Recent
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Cell Death Dis
2023 Dec 14;14(12):831. PMID: 38097548 -
Cell Rep
Repurposing antiparasitic antimonials to noncovalently rescue temperature-sensitive p53 mutations. [Abstract]2022 Apr 12;39(2):110622. PMID: 35417717 -
Int J Mol Sci
Improving Reporter Gene Assay Methodology for Evaluating the Ability of Compounds to Restore P53 Activity. [Abstract]2022 Nov 10;23(22):13867. PMID: 36430341 -
Iran J Basic Med Sci
COTI-2 suppresses the malignancy of bladder cancer by inducing apoptosis via the AMPK-mTOR signaling pathway. [Abstract]2025;28(3):240-246. PMID: 39906622
Protocols
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Apoptosis
Apoptosis, also called programmed cell death, is generally characterized by distinct morphological characteristics.
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TUNEL staining for apoptotic DNA fragmentation
TUNEL staining detects DNA strand breaks by using terminal deoxynucleotidyl transferase to add labeled nucleotides to exposed 3′-OH DNA termini, generating either microscopic staining in fixed cells or tissue sections, or fluorescence/cytometric signal in cell suspensions. TUNEL positivity reflects DNA fragmentation but should not be interpreted alone as definitive apoptosis, because TUNEL can also label necrotic, autolytic, mechanically damaged, or DNA-repair-associated DNA breaks.
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Annexin V plus membrane-impermeant dye apoptosis staining
Annexin V-based apoptosis assays rely on the detection of phosphatidylserine (PS) externalization from the inner leaflet of the plasma membrane to the outer leaflet, an early biochemical hallmark of apoptosis. Fluorescently labeled Annexin V binds PS in a calcium-dependent manner, enabling identification of early apoptotic cells by flow cytometry or fluorescence microscopy. When combined with a membrane-impermeant DNA-binding dye (e. g. , propidium iodide), this approach allows discrimination between viable (Annexin V−/dye−), early apoptotic (Annexin V+/dye−), and late apoptotic or necrotic (Annexin V+/dye+) cell populations by assessing membrane integrity and PS exposure.
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Apoptosis Solutions
Apoptosis is a regulated, generally non-lytic cell-death pathway that removes unwanted, damaged, infected, or abnormal cells through coordinated morphological changes, caspase activation, DNA fragmentation, and membrane remodeling. The intrinsic apoptosis pathway is controlled mainly by mitochondrial outer membrane permeabilization, BCL-2 family proteins, cytochrome c release, apoptosome formation, caspase-9 activation, and downstream executioner caspase-3/7 activation. The extrinsic apoptosis pathway is initiated by death receptors such as Fas, TNFR, and TRAIL receptors, which recruit adaptor proteins and activate caspase-8 before engaging executioner caspases or mitochondrial amplification through BID cleavage. Apoptosis is linked to many phenotypes, including cancer cell killing, tissue homeostasis, immune regulation, neurodegeneration, infection response, and treatment-induced cytotoxicity; unresolved questions include how apoptosis interacts with necroptosis, pyroptosis, ferroptos
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Breast Cancer Modeling
Breast cancer is a heterogeneous cancer, and it has been distinguished into four subtypes: luminal A, luminal B, HER2-positive and basal-like. Molecular mutations, epigenetic alterations, hormone exposure and immune microenvironment are related to the progression of breast cancer.
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Genotoxicity/Mutagenicity Study
The bacterial reverse mutation assay detects point mutations that restore amino-acid prototrophy in auxotrophic Salmonella typhimurium or Escherichia coli tester strains; after exposure to a test article, mutagenic activity is read out as an increased number of revertant colonies on minimal agar compared with the vehicle control. The assay uses tester strains with different mutation targets so that base-substitution and frameshift mutagens can be detected, and testing is performed with and without exogenous mammalian metabolic activation because some chemicals require biotransformation to become mutagenic.
Purity & Documentation
References
[1]. Salim KY, et al. COTI-2, a novel small molecule that is active against multiple human cancer cell lines in vitro and in vivo. Oncotarget. 2016 Jul 05;7(27):41363-41379. [Content Brief]
[2]. Duffy MJ, et al. Mutant p53 as a target for cancer treatment. Eur J Cancer. 2017 Sep;83:258-265. [Content Brief]
[3]. Lindemann A, et al. COTI-2, A Novel Thiosemicarbazone Derivative, Exhibits Antitumor Activity in HNSCC through p53-dependent and -independent Mechanisms. Clin Cancer Res. 2019 Sep 15;25(18):5650-5662. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)