PIK-75

Research use only, not for human use.

PIK-75 is a potent, isoform-selective p110α inhibitor with IC50 of 0.3 nM.

PIK-75 is a potent, isoform-selective p110α inhibitor with IC50 of 0.3 nM, displays >100-fold selectivity over p110β, p110δ and PI3K C2b; blocks the phosphorylation of PKB induced by insulin on both Ser473 and Thr308 in CHO-IR cell (IC50=78 nM), inhibits PI3K activation associated with dramatic suppression of downstream signaling events, including AKT phosphorylation, IKK activation, and NF-kappaB transcription; potently and dose dependently inhibits in vitro and in vivo production of TNF-alpha and IL-6, diminishes the induced expression of human endothelial cell adhesion molecules (E-selectin, ICAM-1, and VCAM-1), and blocks human monocyte-endothelial cell adhesion; exhibits significant anti-tumor effectiveness in vivo.(In Vitro):PIK-75 also inhibits p110δ, PI3KC2β, mTORC1, ATM, hsVPS34, PI3KC2α, mTORC2, ATR and PI4KIIIβ with IC50s of 510 nM, ~1 μM, ~1 μM, 2.3 μM, 2.6 μM, ~10 μM, ~10 μM, 21 μM, ~50 μM, respectively.PIK-75 alone blocks Thr 308 phosphorylation in L6 myotubes and 3T3-L1 adipocytes with IC50 values of 1.2 and 1.3 μM, respectively.PIK-75 (1-1000 nM; 5 min) blocks the phosphorylation of PKB induced by insulin on both Ser473and Thr308 in CHO-IR cells in a dose-dependent manner, with an IC50 of 78 nM.PIK-75 (0.1-1000 nM; 48 hours) inhibits the proliferation and survival of pancreatic cancer cells through apoptotic cell death.PIK-75 (0.1-1000 nM) also reduces the colony formation of pancreatic cancer MIA PaCa-2 and AsPC-1 cells.(In Vivo):PIK-75 (2 mg/kg) potentiates anticancer activity of Gemcitabine (20 mg/kg) in vivo. Gemcitabine (20 mg/kg) or PIK-75 (2 mg/kg) alone reduces the tumor growth to similar degree. Beneficial effect of PIK-75/Gemcitabine is evident as this combination markedly reduces the tumor growth in vivowithout affecting the body weights of mice.

PIK-75 also inhibits p110δ, PI3KC2β, mTORC1, ATM, hsVPS34, PI3KC2α, mTORC2, ATR and PI4KIIIβ with IC50s of 510 nM, ~1 μM, ~1 μM, 2.3 μM, 2.6 μM, ~10 μM, ~10 μM, 21 μM, ~50 μM, respectively.PIK-75 alone blocks Thr 308 phosphorylation in L6 myotubes and 3T3-L1 adipocytes with IC50 values of 1.2 and 1.3 μM, respectively. PIK-75 (1-1000 nM; 5 min) blocks the phosphorylation of PKB induced by insulin on both Ser473and Thr308 in CHO-IR cells in a dose-dependent manner, with an IC50 of 78 nM.PIK-75 (0.1-1000 nM; 48 hours) inhibits the proliferation and survival of pancreatic cancer cells through apoptotic cell death.PIK-75 (0.1-1000 nM) also reduces the colony formation of pancreatic cancer MIA PaCa-2 and AsPC-1 cells. Cell Viability Assay Cell Line:Human pancreatic cancer cells (MIA PaCa-2 or AsPC-1)Concentration:0.1, 0.3, 1, 3, 10, 30, 100, 300, and 1000 nM Incubation Time:48 hours Result:Submicromolar concentration was sufficient to inhibit the proliferation of pancreatic cancer, MIA PaCa-2 and AsPC-1 cells after 48-h treatment. Western Blot Analysis Cell Line:Overnight-starved CHO-IR cells Concentration:1, 10, 100, 1000 nM Incubation Time:5 minutes Result:Blocked the phosphorylation of PKB induced by insulin (1 nM, 10 min) on both Ser473and Thr308 in a dose-dependent manner.

PIK-75 (2 mg/kg) potentiates anticancer activity of Gemcitabine (20 mg/kg) in vivo. Gemcitabine (20 mg/kg) or PIK-75 (2 mg/kg) alone reduces the tumor growth to similar degree. Beneficial effect of PIK-75/Gemcitabine is evident as this combination markedly reduces the tumor growth in vivowithout affecting the body weights of mice. Animal Model:Mice bearing tumors of MIA PaCa-2 Dosage:2 mg/kg; or combination with Gemcitabine (20 mg/kg) Administration:Administered injection; 5 times per week. 25 daysResult:Reduced the tumor growth and enhanced the antitumor effect.

PIK-75 hydrochloride | PIK 75

Cell Cycle/DNA Damage

DNA-PK

DNA-PK|p110α|p110β|p110γ|p110δ

Cancer

——

372196-77-5

488.7

C16H15BrClN5O4S

>98% (HPLC)

10 mM in DMSO

CC1=C(C=C(C=C1)[N+](=O)[O-])S(=O)(=O)N(C)N=CC2=CN=C3N2C=C(C=C3)Br.Cl

Benzenesulfonic acid, 2-methyl-5-nitro-, 2-[(6-bromoimidazo[1,2-a]pyridin-3-yl)methylene]-1-methylhydrazide, hydrochloride (1:1)

(-20℃)

With Ice Pack

≥ 2 years