COTI-2

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.

Product information

CAS Number: 1039455-84-9

Molecular Weight: 366.48

Formula: C19H22N6S

Chemical Name: 4-(pyridin-2-yl)-N-{[(8Z)-5,6,7,8-tetrahydroquinolin-8-ylidene]amino}piperazine-1-carbothioamide

Smiles: S=C(N/N=C1/CCCC2=CC=CN=C2/1)N1CCN(CC1)C1C=CC=CN=1

InChiKey: UTDAKQMBNSHJJB-JWGURIENSA-N

InChi: InChI=1S/C19H22N6S/c26-19(23-22-16-7-3-5-15-6-4-10-21-18(15)16)25-13-11-24(12-14-25)17-8-1-2-9-20-17/h1-2,4,6,8-10H,3,5,7,11-14H2,(H,23,26)/b22-16-

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : 5 mg/mL (13.64 mM; Need ultrasonic).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

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 IC50 concentrations results in the induction of early apoptosis among 40 to 47% of total cells.

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 mm3 while tumors in animals treated with COTI-2 take double that time (10 days) to reach a similar mean volume (857 mm3). COTI-2 treatment effectively inhibits OVCAR-3 xenograft growth regardless of the route of administration.

Products are for research use only. Not for human use.