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
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
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 |
comments |
| 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:
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.
In vivo 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.
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.
