Table 2.

Preclinically evaluated pharmacological agents targeting members of PI3K/Akt3 signaling

Agent	Target/Pathway	Assays measuring efficacy	Dose tested in nude mice	Hurdles limiting clinical use	Ref.
ISC-4	Akt	Cell viability, western blotting	3 ppm of selenium by i.p.	Solubility, Efficacy, Lack of information about bioavailability and distribution	93, 100, 101.
PBISe	Akt and MAPK	Cell viability, western blotting	2.5 ppm selenium by i.p.	Efficacy, Lack of information about bioavailability and distribution	102–104
p-XSC	COX-2, NF-kB	Cell viability, western blotting	Up to 15 mg/kg in diet	Need thorough testing for inhibiting melanoma	105, 106
PHT-427	Akt / PDPK1	western blotting	200 mg/kg oral	Not tested yet in melanoma	107, 108
API-I	Akt	Cell viability, apoptosis	10 mg/kg i.p.	Not tested yet in melanoma	109
API-2	Akt	Cell viability, apoptosis	1 mg/kg i.p.	Toxicity and poor bioavailability	110–113
BI-69A11	Akt	In vitro kinase assay, western blotting	Up to 2 mg/kg i.p.	Not known	116
2-pyrimidyl-5-amidothiophenes	Akt	Proliferation assay	Not known	Not tested thoroughly in vivo	117
A-443654	Akt	Cell viability, western blotting	7.5 mg/kg s.c.	No oral bio-availability and low therapeutic index	94, 118–121
GSK690693	Akt	Cell viability, western blotting	Up to 30 mg/kg i.p.	Transient hyperglycemia	122, 123
Rapamycin	mTOR	Cell survival and western blotting	Up to 30 mg/kg oral	Poor water solubility and stability	127, 128
NVP-BBD-130	PI3K, mTOR	Cell survival and western blotting	40 mg/kg oral	Information on therapeutic index and tolerability is lacking	130
NVP-BEZ-235	PI3K, mTOR	Cell survival and western blotting	30 mg/kg, oral	Information on therapeutic index and tolerability is lacking	130
ZSTK474	PI3K, mTOR	Cell survival and western blotting	Up to 400 mg/kg, oral	Information on therapeutic index and tolerability is lacking	130
OXA-01	PI3K, mTOR	Cell survival and western blotting	Up to 75 mg/kg i.p.		131