Hu7691 free base

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

Hu7691 free base 是一种具有口服活性的，选择性 Akt 抑制剂，对 Akt1、Akt2 和 Akt3 的 IC50 分别为 4.0 nM、97.5 nM、28 nM。Hu7691 free base 抑制肿瘤生长并降低小鼠的皮肤毒性。

Hu7691 free base is an orally active, selective Akt inhibitor with IC50s of 4.0 nM, 97.5 nM, 28 nM for Akt1, Akt2 and Akt3, respectively. Hu7691 free base inhibits tumor growth and enables decrease of cutaneous toxicity in mice.

Hu7691 free base displays low inhibitions against most of the kinases in the four families (AGC, TK, TKL, Lipid/Atypical; PKA, IC50=11 nM; PKCη, IC50=629 nM; ROCK1, IC50=354 nM; RSK1, IC50=756 nM; P70S6K, IC50=229 nM; SGK, IC50=1009 nM). Hu7691 free base (2.25-36 μM; 24 hours) induces effective decrease of the phosphorylation level of Akt (S473). Hu7691 free base (10, 20, 30, 40 μM; for 72 h) exhibits low toxicity against HaCaT cells with an IC50 value of 15.2 μM. Hu7691 free base has a significant inhibitory effect on the growth of 18 kinds of human tumor cells (U87-MG, U251, A549, HepG2, HT-29, KHOS, MDA-MB-231, PC3, SKOV3 and so on) derived from different tissues, with the IC50 range of 0.6-27 μM. Hu7691 free base shows low antiproliferation activities against the HL7702 and HPDE6-C7 normal cells, exhibiting IC50 values of 5.4 and 16.1 μM, respectively. Western Blot Analysis Cell Line:HaCaT cells Concentration:2.25, 4.5, 9, 18, 36 μM Incubation Time:24 hours Result:Induced effective decrease of the phosphorylation level of Akt (S473).

Hu7691 free base (12.5-50 mg/kg/day; i.g.; for 22 days) shows dose-dependent tumor growth inhibition. Hu7691 free base (15 mg/kg; oral) has a T1/2 of 8.68 hours, a Cmax of 171.17 ng/mL and an AUC of 2820.64 ng/mL?h in rats. Hu7691 free base (2 mg/kg; iv) has a T1/2 of 6.24 hours, a Cmax of 207.52 ng/mL and an AUC of 532.87 ng/mL?h in rats. Hu7691 free base (20 mg/kg; oral) has a T1/2 of 16.7 hours, a Cmax of 905.65 ng/mL and an AUC of 36303 ng/mL?h in beagle dog (male, 40 weeks old, 8–10 kg). Animal Model:Balb/c mice (nu/nu, female, 3-4 weeks old, 20-25 g) with 786-O and KHOS xenograft Dosage:12.5, 25, 50 mg/kg Administration:Oral; once daily for 22 days Result:Showed dose-dependent tumor growth inhibition.Animal Model:SD rats (male, 8 weeks old, 250-300 g) Dosage:15 mg/kg (Pharmacokinetic Analysis)Administration:Oral Result:Had a T1/2 of 8.68 hours, a Cmax of 171.17 ng/mL and an AUC of 2820.64 ng/mL?h.

——

Cytoskeleton/Cell Adhesion Molecules

Akt

Akt

——

——

2241232-43-7

414.423

C22H21F3N4O

>98% (HPLC)

——

N(C(=O)C1=C(F)C=C(C=C1)C2=CC=NN2C)[C@H]3[C@@H](CCNC3)C4=CC(F)=C(F)C=C4

——

(-20℃)

With Ice Pack

≥ 2 years