[CAS NO. 1039455-84-9] COTI-2
PRODUCTS SPECIFICATIONS [1039455-84-9]
DESCRIPTION [1039455-84-9]
Overview
| MDL | MFCD28502211 |
|---|---|
| Molecular Weight | 366.48 |
| Molecular Formula | C19H22N6S |
| SMILES | S=C(N1CCN(C2=NC=CC=C2)CC1)N/N=C3CCCC4=C\3N=CC=C4 |
1 Publications Citing Use of MCE
Summary
COTI-2, an anti-cancer drug with low toxicity, is an orally available third generation activator of p53 mutant forms. COTI-2 acts both by reactivating mutant p53 and inhibiting the PI3K/AKT/mTOR pathway. COTI-2 induces apoptosis in multiple human tumor cell lines. COTI-2 exhibits antitumor activity in HNSCC through p53-dependent and -independent mechanisms. COTI-2 converts mutant p53 to wild-type conformation [1] [2] [3] .
IC50 & Target
p53 [1]
In Vitro
COTI-2 efficiently inhibits the proliferation rate of all the tested cell lines following 72 h of treatment. COTI-2 is significantly effective at inhibiting tumor cell proliferation in all three cell lines (COLO-205, HCT-15, and SW620). Relatively low concentrations of COTI-2 are active against all human glioblastoma cell lines tested (U87-MG, SNB-19, SF-268, and SF-295). COTI-2 treatment of SHP-77 cells with approximate IC 50 concentrations results in the induction of early apoptosis among 40 to 47% of total cells [2] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
COTI-2 significantly inhibits tumor growth in the HT-29 human colorectal tumor xenografts at a dose of 10 mg/kg. In addition to reducing tumor volumes at specific times post-treatment, COTI-2 also delays the time required for tumors to reach specified volumes. COTI-2 also significantly inhibits tumor growth in the SHP-77 SCLC xenograft model at a dose as low as 3 mg/kg. COTI-2 treatment both reduces U87-MG tumor volumes at specific times post-treatment and lengthens the time required for U87-MG xenografts to grow in nude mice. Control tumors in mice treated with vehicle alone take only 5 days to reach an average volume of 828 mm 3 while tumors in animals treated with COTI-2 take double that time (10 days) to reach a similar mean volume (857 mm 3 ). COTI-2 treatment effectively inhibits OVCAR-3 xenograft growth regardless of the route of administration [2] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT02433626 | Critical Outcome Technologies Inc.|M.D. Anderson Cancer Center|Northwestern Memorial Hospital |
Ovarian Cancer|Fallopian Tube Cancer|Endometrial Cancer|Cervical Cancer|Peritoneal Cancer|Head and Neck Cancer|HNSCC|Colorectal Cancer|Lung Cancer|Pancreatic Cancer
|
December 2015 | Phase 1 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 5 mg/mL ( 13.64 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.7287 mL | 13.6433 mL | 27.2866 mL |
| 5 mM | 0.5457 mL | 2.7287 mL | 5.4573 mL |
| 10 mM | 0.2729 mL | 1.3643 mL | 2.7287 mL |
-
1.
Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 0.67 mg/mL (1.83 mM); Clear solution
References
- [1] Duffy MJ, et al. Mutant p53 as a target for cancer treatment. Eur J Cancer. 2017 Sep;83:258-265.
- [2] 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 5;7(27):41363-41379.
- [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.