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PI3K/mTOR Inhibitor-12 is a potent, orally active and selective PI3K/mTOR inhibitor with IC50 values of 0.06 nM and 3.12 nM for PI3Kα and mTOR, respectively. PI3K/mTOR Inhibitor-12 has antitumor activity. PI3K/mTOR Inhibitor-12 has lower liver toxicity[1]. | [in vivo]
PI3K/mTOR Inhibitor-12 (compound 48; 20 mg/kg; p.o.; daily, for 14 d) inhibits tumor growth of HCT116 xenografts in female BALB/c nude mice[1].
PI3K/mTOR Inhibitor-12 (1 and 5 mg/kg; i.v. and p.o.; male SD rats) has fast plasma clearance (1428 mL/h/kg) and short T1/2 (2.33 h) and the AUC0-∞ is 1356 h*ng/mL[1].
| Animal Model: | HCT116 xenografts in female BALB/c nude mice[1] | | Dosage: | 20 mg/kg | | Administration: | Oral administration, daily, for 14 days | | Result: | Reduced the growth of HCT116 tumors, and the tumor growth inhibition (TGI) was 73.33%.
Had lower liver toxicity of HCT116 xenografts in female BALB/c nude mice.
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| Animal Model: | Male SD rats[1] | | Dosage: | 1 and 5 mg/kg | | Administration: | Intravenous injection (1 mg/kg) and oral administration (5 mg/kg) | | Result: | 1.19| Parameter | I.V. (1 mg/kg) | Parameter | P.O. (5 mg/kg) | | T1/2 (h) | 0.6 | T1/2 (h) | 2.33 | | CL (mL/h/kg) | 1428 | Cmax (ng/mL) | 1218 | | Vdss (mL/Kg) | 528 | AUC0-∞ (h*ng/mL) | 1356 | | AUC0-∞ (h*ng/mL) | 760 | F% | 33.1 |
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| [IC 50]
PI3Kα: 0.06 nM (IC50); mTOR: 3.12 nM (IC50) | [References]
[1] Li C, et, al. Function-oriented synthesis of Imidazo[1,2-a]pyrazine and Imidazo[1,2-b]pyridazine derivatives as potent PI3K/mTOR dual inhibitors. Eur J Med Chem. 2022 Dec 20;247:115030. DOI:10.1016/j.ejmech.2022.115030 |
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