GDC-0623
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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).


Chemical Structure

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GDC-0623
CAS# 1168091-68-6

Theoretical Analysis

MedKoo Cat#: 205772
Name: GDC-0623
CAS#: 1168091-68-6
Chemical Formula: C16H14FIN4O3
Exact Mass: 456.01
Molecular Weight: 456.216
Elemental Analysis: C, 42.12; H, 3.09; F, 4.16; I, 27.82; N, 12.28; O, 10.52

Price and Availability

Size Price Availability Quantity
50mg USD 450
100mg USD 750 2 Weeks
200mg USD 1250 2 Weeks
500mg USD 2850 2 Weeks
1g USD 4250 2 Weeks
2g USD 7250 2 Weeks
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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

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)      

Product Data:
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

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 70.5 154.53
Ethanol 6.0 13.15

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.

Recalculate based on batch purity %
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

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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.