WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 205772
CAS#: 1168091-68-6
Description: GDC-0623, also known as G-868, is an orally active, selective MEK inhibitor with potential antineoplastic activity. MEK inhibitor GDC-0623 specifically inhibits mitogen-activated protein kinase kinase (MEK or MAP/ERK kinase), resulting in inhibition of growth factor-mediated cell signaling and tumor cell proliferation. MEK is a key component of the RAS/RAF/MEK/ERK signaling pathway that regulates cell growth; constitutive activation of this pathway has been implicated in many cancers. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).
MedKoo Cat#: 205772
Name: GDC-0623
CAS#: 1168091-68-6
Chemical Formula: C16H14FIN4O3
Exact Mass: 456.00946
Molecular Weight: 456.2159
Elemental Analysis: C, 42.12; H, 3.09; F, 4.16; I, 27.82; N, 12.28; O, 10.52
Synonym: GDC0623; GDC-0632; GDC 0632; 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
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
| 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/ |
| In vivo activity: | TBD |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 70.5 | 154.53 | |
| Ethanol | 6.0 | 13.15 |
The following data is based on the product molecular weight 456.2159 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. |
| In vivo protocol: | TBD |
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.
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)
