Home PI3K/Akt/mTOR PI3K inhibitor - mTOR inhibitor Paxalisib (GDC-0084) For research use only.

Paxalisib (GDC-0084)

Synonyms: RG7666

Paxalisib (GDC-0084, RG7666) is a brain penetrant inhibitor of PI3K and mTOR with Kiapp values of 2 nM, 46 nM, 3 nM, 10 nM and 70 nM for PI3Kα, PI3Kβ, PI3Kδ, PI3Kγ and mTOR.

Paxalisib (GDC-0084) Chemical Structure

Paxalisib (GDC-0084) Chemical Structure

CAS No. 1382979-44-3

Purity & Quality Control

Paxalisib (GDC-0084) Related Products

Signaling Pathway

PI3K Signaling Pathways

PI3K Signaling Pathway

Biological Activity

Description Paxalisib (GDC-0084, RG7666) is a brain penetrant inhibitor of PI3K and mTOR 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
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[1]. 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)[2].
Cell Research Cell lines Madin-Darby canine kidney (MDCK) cells （MDR1-MDCKI cells）
Concentrations 5 μM
Incubation Time 2 h
Method For transport studies, cells are seeded on 24-well Millicell plates 4 days prior to use(polyethylene terephtalate membrane, 1 μm pore size) at a seeding density of 1.3×105 cells/ml). GDC-0084 is tested at 5 μM in the apical-tobasolateral (A-B) and basolateral-to-apical (B-A) directions. The compound is dissolved in transport buffer consisting of Hanks' balanced salt solution with 10 mM HEPES. Lucifer Yellow is used as the paracellular and monolayer integrity marker. GDC-0084 concentrations in the donor and receiving compartments are determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The apparent permeability (Papp), in the apical to A-B and B-A directions, is calculated after 2-hour incubation.
In Vivo
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[2].
Animal Research Animal Models Male Sprague−Dawley rats or female CD-1 mice
Dosages 1 mg/kg（i.v.）;5 or 25 mg/kg(p.o.)
Administration i.v. or p.o.
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT05012670 Completed
Healthy
Kazia Therapeutics Limited|Quotient Sciences
 August 18 2021 Phase 1
NCT03696355 Completed
Brain and Central Nervous System Tumors
St. Jude Children''s Research Hospital|Kazia Therapeutics Limited
 November 19 2018 Phase 1

Chemical Information & Solubility

Molecular Weight 382.42 Formula

C18H22N8O2
CAS No. 1382979-44-3 SDF Download Paxalisib (GDC-0084) SDF
Smiles CC1(C2=NC3=C(N2CCO1)N=C(N=C3N4CCOCC4)C5=CN=C(N=C5)N)C
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 5 mg/mL ( (13.07 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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