[CAS NO. 1382979-44-3] Paxalisib (GDC-0084)

Name: Paxalisib (GDC-0084)
Brand: Arctom Scientific
SKU: SLK-S8163

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PRODUCTS SPECIFICATIONS [1382979-44-3]

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Catalog

SLK-S8163

Brand

Selleck

CAS

1382979-44-3

DESCRIPTION [1382979-44-3]

Overview

MDL	MFCD30187522
Molecular Weight	382.42
Molecular Formula	C18H22N8O2
SMILES	NC1=NC=C(C2=NC(N3CCOCC3)=C4N=C(C(C)(C)OCC5)N5C4=N2)C=N1

For research use only.

Storage

3 years,-20°C,powder
1 years,-80°C,in solvent

Shipping

Room temperature shipping(Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Concentration Volume Mass	1 mg	5 mg	10 mg
1 mM	2.6149 mL	13.0746 mL	26.1493 mL
5 mM	0.5230 mL	2.6149 mL	5.2299 mL
10 mM	0.2615 mL	1.3075 mL	2.6149 mL
50 mM	-	-	-

Description

Paxalisib (GDC-0084, RG7666) is a brain penetrant inhibitor of and with Kiapp values of 2 nM, 46 nM, 3 nM, 10 nM and 70 nM for PI3Kα, PI3Kβ, PI3Kδ, PI3Kγ and mTOR.

Targets

PI3Kα ^[1] (Cell-free assay)	PI3Kδ ^[1] (Cell-free assay)	PI3Kγ ^[1] (Cell-free assay)	PI3Kβ ^[1] (Cell-free assay)	mTOR ^[1] (Cell-free assay)
2 nM(Ki app)	3 nM(Ki app)	10 nM(Ki app)	46 nM(Ki app)	70 nM(Ki app)

In vitro

GDC-0084 has excellent human metabolic stability in microsomal and hepatocyte incubations and demonstrated inhibition of pAKT, a key signal within the PI3K pathway, in normal brain tissue. GDC-0084 is shown to inhibit the proliferation of several glioma cells in vitro with IC50 ranging from 0.3 to 1.1 μM. GDC-0084 binding to plasma proteins is low, with a free fraction (%) of 29.5±2.7 (n=3) in CD-1 mouse plasma, when tested at 5 μM. Binding to brain tissues from CD-1 mice is higher, with a free fraction of 6.7% (±1; n=3).

In vivo

GDC-0084 markedly inhibits the PI3K pathway in mouse brain, causing up to 90% suppression of the pAkt signal. GDC-0084 achieves significant tumor growth inhibition of 70% and 40% against the U87 and GS2 orthotopic models, respectively. GDC-0084 distribution throughout the brain and intracranial tumors leads to potent inhibition of the PI3K pathway. It is being evaluated in patients, and exposures reached at tolerated doses are consistent with those associated with efficacious doses in mouse models.

References

[1] Heffron TP, et al. ACS Med Chem Lett. 2016, 7(4):351-6.
[2] Salphati L, et al. Drug Metab Dispos. 2016, 44(12):1881-1889.