COTI-2

Research use only, not for human use.

COTI-2 (COTI2) is an orally available thiosemicarbazone that may act on mutant forms of p53 and PI3K/AKT/mTOR pathway.

COTI-2 (COTI2) is an orally available thiosemicarbazone that may act on mutant forms of p53 and PI3K/AKT/mTOR pathway; induces apoptosis in a wide variety of human tumor cells in culture (IC50s<40 nM), inhibits the proliferation of colorectal cancer cell lines more effectively than cetuximab and erlotinib; shows superior activity against tumor, and is safe and well-tolerated in vivo.Ovarian Cancer Phase 1 Clinical(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.

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COTI2

Apoptosis

MDM2-p53

p53mutants

Cancer

Ovarian Cancer

1039455-84-9

366.5

C19H22N6S

>98% (HPLC)

DMSO: 10 mM （ < 1 mg/ml refers to the product slightly soluble or insoluble )

S=C(N1CCN(C2=NC=CC=C2)CC1)N/N=C3CCCC4=C\3N=CC=C4

4-(2-pyridinyl)-2-(6,7-dihydro-8(5H)-quinolinylidene)hydrazide-1-piperazinecarbothioic acid

(-20℃)

With Ice Pack

≥ 2 years