GDC-0032 Chemical Properties

Boiling point:

783.3±70.0 °C(Predicted)

Density 

1.40±0.1 g/cm3(Predicted)

storage temp. 

Store at -20°C

solubility 

≥23.05 mg/mL in DMSO; insoluble in H2O; ≥2.79 mg/mL in EtOH with gentle warming

form 

solid

pka

15.54±0.50(Predicted)

color 

White to off-white

GDC-0032 Usage And Synthesis

Description

GDC-0032 is a potent inhibitor of phosphatidylinositol 3-kinase (PI3K) isoforms α, δ, and γ (IC₅₀s = 0.28, 0.12, and 0.97 nM, respectively) that is 31 times less potent at PI3Kβ. It is over 1,000-fold selective for p100α over other PI3K-like kinases, including DNA-dependent protein kinase catalytic subunits, ATM, and ATR. GDC-0032 has increased potency in cancer cell lines harboring PIK3CA-activating alterations, and is effective in vivo, suppressing the growth of tumors in a mouse xenograft model at low drug dose levels.

Uses

4-[5,6-Dihydro-2-[3-methyl-1-(1-methylethyl)-1H-1,2,4-triazol-5-yl]imidazo[1,2-d][1,4]benzoxazepin-9-yl]-α,α-dimethyl-1H-pyrazole-1-acetamide is a newly discovered A β-Sparing phosphoinositide 3-kinase inhibitor with high unbound exposure and robust in vivo antitumor activity.

in vivo

target

PI3Kδ

IC 50

PI3Kδ: 0.12 nM (Ki); PI3Kα: 0.29 nM (Ki); PI3Kγ: 0.97 nM (Ki); PI3Kβ: 9.1 nM (Ki)

References

[1] ndubaku co1, heffron tp, staben st, baumgardner m, blaquiere n, bradley e, bull r, do s, dotson j, dudley d, edgar ka, friedman ls, goldsmith r, heald ra, kolesnikov a, lee l, lewis c, nannini m, nonomiya j, pang j, price s, prior ww, salphati l, sideris s, wallin jj, wang l, wei b, sampath d, olivero ag. discovery of 2-{3-[2-(1-isopropyl-3-methyl-1h-1,2-4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl]-1h-pyrazol-1-yl}-2-methylpropanamide (gdc-0032): a β-sparing phosphoinositide 3-kinase inhibitor with high unbound exposure and robust in vivo antitumor activity. j med chem. 2013 jun 13;56(11):4597-610.

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