Synonym
GDC0623; GDC-0632; GDC 0632; RG 7421; RG7421; RG-7421; G868; G 868; G-868
IUPAC/Chemical Name
5-((2-fluoro-4-iodophenyl)amino)-N-(2-hydroxyethoxy)imidazo[1,5-a]pyridine-6-carboxamide
InChi Key
RFWVETIZUQEJEF-UHFFFAOYSA-N
InChi Code
InChI=1S/C16H14FIN4O3/c17-13-7-10(18)1-4-14(13)20-15-12(16(24)21-25-6-5-23)3-2-11-8-19-9-22(11)15/h1-4,7-9,20,23H,5-6H2,(H,21,24)
SMILES Code
O=C(C1=C(NC2=CC=C(I)C=C2F)N3C(C=C1)=CN=C3)NOCCO
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
GDC-0623, a selective inhibitor of MEK, also known as mitogen activated protein kinase kinase (MAPKK), is a key component of the RAS/RAF/MEK/ERK pathway, which is frequently activated in human tumors. Inappropriate activation of the MEK/ERK pathway promotes cell growth in the absence of exogenous growth factors.
G479 is Me-Too version of GDC-0623. Their structures are shown below (side-by-side comparison)
G479 is Me-Too version
of GDC-0623. Their structures are shown below (side-by-side comparison)
Biological target:
GDC-0623 (RG 7421) is a potent, ATP-uncompetitive inhibitor of MEK1 (Ki=0.13 nM, +ATP), and displays 6-fold weaker potency against HCT116 (KRAS (G13D), EC50=42 nM) versus A375 (BRAFV600E, EC50=7 nM).
In vitro activity:
Compared to the control group, after 7 days of osteogenic induction, ALP staining showed that signals in IL-1β-treated groups were significantly inhibited. However, the ALP signal recovered after GDC0623 treatment (Figure 2(a)). ALP activities were further quantitatively analyzed, showing that ALP activities of osteoblasts in the IL-1β groups were lower than those of the control group. However, ALP activities in osteoblasts significantly recovered after GDC0623 treatment (Figure 2(b)).
Reference: Int J Endocrinol. 2021 Dec 22;2021:5720145. https://pubmed.ncbi.nlm.nih.gov/34976051/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
70.5 |
154.53 |
| Ethanol |
6.0 |
13.15 |
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
456.22
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. Zhang ZQ, Hu XS, Lu YC, Zhang JP, Li WY, Zhang WY, Feng W, Ding DF, Xu JG. MEK1/2 Inhibitor (GDC0623) Promotes Osteogenic Differentiation of Primary Osteoblasts Inhibited by IL-1β through the MEK-Erk1/2 and Jak/Stat3 Pathways. Int J Endocrinol. 2021 Dec 22;2021:5720145. doi: 10.1155/2021/5720145. PMID: 34976051; PMCID: PMC8716208.
2. Zaanan A, Okamoto K, Kawakami H, Khazaie K, Huang S, Sinicrope FA. The Mutant KRAS Gene Up-regulates BCL-XL Protein via STAT3 to Confer Apoptosis Resistance That Is Reversed by BIM Protein Induction and BCL-XL Antagonism. J Biol Chem. 2015 Sep 25;290(39):23838-49. doi: 10.1074/jbc.M115.657833. Epub 2015 Aug 5. PMID: 26245900; PMCID: PMC4583008.
In vitro protocol:
1. Zhang ZQ, Hu XS, Lu YC, Zhang JP, Li WY, Zhang WY, Feng W, Ding DF, Xu JG. MEK1/2 Inhibitor (GDC0623) Promotes Osteogenic Differentiation of Primary Osteoblasts Inhibited by IL-1β through the MEK-Erk1/2 and Jak/Stat3 Pathways. Int J Endocrinol. 2021 Dec 22;2021:5720145. doi: 10.1155/2021/5720145. PMID: 34976051; PMCID: PMC8716208.
2. Zaanan A, Okamoto K, Kawakami H, Khazaie K, Huang S, Sinicrope FA. The Mutant KRAS Gene Up-regulates BCL-XL Protein via STAT3 to Confer Apoptosis Resistance That Is Reversed by BIM Protein Induction and BCL-XL Antagonism. J Biol Chem. 2015 Sep 25;290(39):23838-49. doi: 10.1074/jbc.M115.657833. Epub 2015 Aug 5. PMID: 26245900; PMCID: PMC4583008.
1: Robarge KD, Lee W, Eigenbrot C, Ultsch M, Wiesmann C, Heald R, Price S, Hewitt J, Jackson P, Savy P, Burton B, Choo EF, Pang J, Boggs J, Yang A, Yang X, Baumgardner M. Structure based design of novel 6,5 heterobicyclic mitogen-activated protein kinase kinase (MEK) inhibitors leading to the discovery of imidazo[1,5-a] pyrazine G-479. Bioorg Med Chem Lett. 2014 Oct 1;24(19):4714-23. doi: 10.1016/j.bmcl.2014.08.008. Epub 2014 Aug 15. PubMed PMID: 25193232.
2: Hatzivassiliou G, Haling JR, Chen H, Song K, Price S, Heald R, Hewitt JF, Zak M, Peck A, Orr C, Merchant M, Hoeflich KP, Chan J, Luoh SM, Anderson DJ, Ludlam MJ, Wiesmann C, Ultsch M, Friedman LS, Malek S, Belvin M. Mechanism of MEK inhibition determines efficacy in mutant KRAS- versus BRAF-driven cancers. Nature. 2013 Sep 12;501(7466):232-6. doi: 10.1038/nature12441. Epub 2013 Aug 11. Erratum in: Nature. 2013 Oct 10;502(7470):258. PubMed PMID: 23934108.
