GDC-0084 | Paxalisib | CAS#1382979-44-3 | PI3K delat inhibitor

MedKoo Cat#: 206559 | Name: GDC-0084

Description:

WARNING: This product is for research use only, not for human or veterinary use.

GDC-0084, also known as RG7666 and Paxalisib, is a phosphatidylinositol 3-kinase (PI3K) inhibitor with potential antineoplastic activity. PI3K inhibitor GDC-0084 specifically inhibits PI3K in the PI3K/AKT kinase (or protein kinase B) signaling pathway, thereby inhibiting the activation of the PI3K signaling pathway. This may result in the inhibition of both cell growth and survival in susceptible tumor cell populations. Activation of the PI3K signaling pathway is frequently associated with tumorigenesis.

Chemical Structure

GDC-0084

CAS#1382979-44-3

Theoretical Analysis

MedKoo Cat#: 206559

Name: GDC-0084

CAS#: 1382979-44-3

Chemical Formula: C18H22N8O2

Exact Mass: 382.1866

Molecular Weight: 382.43

Elemental Analysis: C, 56.53; H, 5.80; N, 29.30; O, 8.37

Price and Availability

Size	Price	Availability
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,250.00	Ready to ship
500mg	USD 2,450.00	Ready to ship
1g	USD 3,850.00	Ready to ship
2g	USD 6,450.00	Ready to ship

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Related CAS #

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Synonym

RG7666; RG-7666; RG 7666; GDC-0084; GDC0084; GDC 0084; Paxalisib

IUPAC/Chemical Name

5-(6,6-dimethyl-4-morpholino-8,9-dihydro-6H-[1,4]oxazino[4,3-e]purin-2-yl)pyrimidin-2-amine

InChi Key

LGWACEZVCMBSKW-UHFFFAOYSA-N

InChi Code

InChI=1S/C18H22N8O2/c1-18(2)16-22-12-14(25-3-6-27-7-4-25)23-13(11-9-20-17(19)21-10-11)24-15(12)26(16)5-8-28-18/h9-10H,3-8H2,1-2H3,(H2,19,20,21)

SMILES Code

NC1=NC=C(C2=NC(N3CCOCC3)=C4N=C(C(C)(C)OCC5)N5C4=N2)C=N1

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#C24R02B21

QC Data

View QC data: current batch, Lot#C24R02B21

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

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

In vitro activity:

PI3K-Akt-mTOR signaling is overactivated in cSCC cells, representing a valuable therapeutic target. GDC-0084 is a novel PI3K/mTOR dual inhibitor. Its effect in cSCC cells was studied. Three established cSCC cell lines, A431, SCC-13 and SCL-1, were tested. By performing the CCK-8 assay, this study showed that GDC-0084 inhibited survival of all cSCC cells (Fig. 1A). The PI3K/mTOR dual inhibitor displayed a dose-dependent activity in inhibiting cSCC cell survival (Fig. 1A). At the lowest concentration (10 nM) it was however ineffective (Fig. 1A). Among the tested cell lines A431 cells were most sensitive to GDC-0084, showing the lowest IC-50 (186.51 ± 11.31 nM) (Fig. 1A). Reference: Biochem Biophys Res Commun. 2018 Sep 10;503(3):1941-1948. https://pubmed.ncbi.nlm.nih.gov/30072096/

In vivo activity:

In a patient-derived brain metastasis mouse model, 15mg/kg/day of GDC-0084 administered orally significantly inhibited tumor growth in a trastuzumab-resistant, PIK3CA-MT cell line model and not a PIK3CA-WT cell line model. PI3K-pathway inhibition within the brain was confirmed with immunohistochemistry by reduction in signal intensity for pAkt and pS6 ribosomal protein in the PIK3CA-MT tumors treated with GDC-0084. Reference: Clin Cancer Res. 2019 Jun 1; 25(11): 3374–3383. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6685218/

	Solvent	mg/mL	mM
Solubility
	DMSO	7.0	18.30

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 382.43 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Ippen FM, Alvarez-Breckenridge CA, Kuter BM, Fink AL, Bihun IV, Lastrapes M, Penson T, Schmidt SP, Wojtkiewicz GR, Ning J, Subramanian M, Giobbie-Hurder A, Martinez-Lage M, Carter SL, Cahill DP, Wakimoto H, Brastianos PK. The Dual PI3K/mTOR Pathway Inhibitor GDC-0084 Achieves Antitumor Activity in PIK3CA-Mutant Breast Cancer Brain Metastases. Clin Cancer Res. 2019 Jun 1;25(11):3374-3383. doi: 10.1158/1078-0432.CCR-18-3049. Epub 2019 Feb 22. PMID: 30796030; PMCID: PMC6685218. 2. Ding LT, Zhao P, Yang ML, Lv GZ, Zhao TL. GDC-0084 inhibits cutaneous squamous cell carcinoma cell growth. Biochem Biophys Res Commun. 2018 Sep 10;503(3):1941-1948. doi: 10.1016/j.bbrc.2018.07.139. Epub 2018 Jul 30. PMID: 30072096. 3. Salphati L, Alicke B, Heffron TP, Shahidi-Latham S, Nishimura M, Cao T, Carano RA, Cheong J, Greve J, Koeppen H, Lau S, Lee LB, Nannini-Pepe M, Pang J, Plise EG, Quiason C, Rangell L, Zhang X, Gould SE, Phillips HS, Olivero AG. Brain Distribution and Efficacy of the Brain Penetrant PI3K Inhibitor GDC-0084 in Orthotopic Mouse Models of Human Glioblastoma. Drug Metab Dispos. 2016 Dec;44(12):1881-1889. doi: 10.1124/dmd.116.071423. Epub 2016 Sep 16. PMID: 27638506.

In vitro protocol:

In vivo protocol:

1: Salphati L, Alicke B, Heffron TP, Shahidi-Latham S, Nishimura M, Cao T, Carano RA, Cheong J, Greve J, Koeppen H, Lau S, Lee LB, Nannini-Pepe M, Pang J, Plise EG, Quiason C, Rangell L, Zhang X, Gould SE, Phillips HS, Olivero AG. Brain Distribution and Efficacy of the Brain Penetrant PI3K Inhibitor GDC-0084 in Orthotopic Mouse Models of Human Glioblastoma. Drug Metab Dispos. 2016 Dec;44(12):1881-1889. Epub 2016 Sep 16. PubMed PMID: 27638506. 2: Heffron TP, Ndubaku CO, Salphati L, Alicke B, Cheong J, Drobnick J, Edgar K, Gould SE, Lee LB, Lesnick JD, Lewis C, Nonomiya J, Pang J, Plise EG, Sideris S, Wallin J, Wang L, Zhang X, Olivero AG. Discovery of Clinical Development Candidate GDC-0084, a Brain Penetrant Inhibitor of PI3K and mTOR. ACS Med Chem Lett. 2016 Feb 16;7(4):351-6. doi: 10.1021/acsmedchemlett.6b00005. eCollection 2016 Apr 14. PubMed PMID: 27096040; PubMed Central PMCID: PMC4834666.