BX-320

Research use only, not for human use.

BX-320 is a potent, selective and ATP-competitive inhibitor of PDK1 with IC50 of 30 nM.

BX-320 is a potent, selective and ATP-competitive inhibitor of PDK1 with IC50 of 30 nM, >20-fold selectivity over PKA; blocks PDK1/Akt signaling in tumor cells and inhibits the anchorage-dependent growth of a variety of tumor cell lines in culture or induces apoptosis; inhibits the growth of LOX melanoma tumors in the lungs of nude mice.

BX-320 binds to the ATP binding site of PDK1. BX-320 also inhibits Chck1, c-Kit, KDR, PKA, CDK2b/cyclin E, GSK3β, PKC with IC50s of 0.82, 0.89, 1.4, 1.4, 1.5, 4.0, and 5.7 μM, respectively. BX-320 blocks PDK1/Akt signaling in tumor cells and inhibits the anchorage-dependent growth of a variety of tumor cell lines in culture or induces apoptosis. BX-320 inhibits the growth of MDA-468 breast cancer cells (IC50=0.6 μM) and induces apoptosis. BX-320 promotes a 12-fold induction of caspase-3/7 activity after 48 h of treatment (IC50=0.5 μm), indicating a strong proapoptotic response. BX-320 (0.3-10 μM; for 18 hours) greatly reduces the amount of both p-Thr308-Akt and p-Thr386-S6K1. Cell Proliferation AssayCell Line:MDA-468 breast cancer cells Concentration:31.6 nM, 100 nM, 316.22 nM, 1 μM, 3.162 μM, 10 μM, and 31.6 μM Incubation Time:72 hours Result:Blocked the growth of MDA-468 cells (IC50=0.6 μM), which are PTEN-negative breast tumor cells expressing high levels of activated Akt.Western Blot Analysis Cell Line:PC-3 cells Concentration:0, 0.3, 1, 3, 10 μM Incubation Time:18 hours Result:Reduced the amount of both phospho-Thr308-Akt and phospho-Thr386-S6K1.

BX-320 (oral dosing with 200 mg/kg, twice a day for 21 days) shows efficacy in a blood-borne metastasis model. BX-320 inhibits the growth of LOX melanoma tumors in the lungs of nude mice after injection of tumor cells into the tail vein. BX-320 has efficacy in an in vivo tumor model, which may reflect an inhibition of productive implantation of tumor cells in the lung or an inhibition of subsequent tumor growth. Animal Model:Athymic (nu/nu) female mice, 6-8 weeks old Dosage:200 mg/kg; dose volume was 10 mL/kg Administration:Oral gavage twice daily (12 h apart)Result:Significantly inhibited the growth of lung tumors in this model.

BX320

PI3K/Akt/mTOR signaling

PDK

PDK

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702676-93-5

547.458

C23H31BrN8O3

>98% (HPLC)

——

CC(C)(C(=O)N)C(=O)NCCCNC1=NC(=NC=C1Br)NC2=CC(=CC=C2)NC(=O)N3CCCC3

Propanediamide, N-[3-[[5-bromo-2-[[3-[(1-pyrrolidinylcarbonyl)amino]phenyl]amino]-4-pyrimidinyl]amino]propyl]-2,2-dimethyl- (9CI)

(-20℃)

With Ice Pack

≥ 2 years