870483-87-7

Basic information

• Product Name: 5-[3-Methoxy-4-(4-methoxy-benzyloxy)-benzyl]-pyrimidine-2,4-diamine
• Synonyms: 5-[3-Methoxy-4-(4-methoxy-benzyloxy)-benzyl]-pyrimidine-2,4-diamine;GW2580;SC-203877;SC-203877/GW2580;2,4-Pyrimidinediamine, 5-[[3-methoxy-4-[(4-methoxyphenyl)methoxy]phenyl]methyl]-;5-[[3-Methoxy-4-[(4-methoxyphenyl)methoxy]phenyl]methyl]-2,4-Pyrimidinediamine;5-[[3-Methoxy-4-[(4-methoxyphenyl)methoxy]phenyl]methyl]pyrimidine-2,4-diamine;GW2580, >=98%
• CAS NO: 870483-87-7
• Molecular Formula: C20H22N4O3
• Molecular Weight: 366.41368
• Product Categories: Inhibitors
• Mol File: 870483-87-7.mol
• Article Data: 0

Chemical Properties

• Appearance: white to beige/
• Storage Temp.: ?20°C
• Solubility: DMSO: soluble10mg/mL, clear (warmed)
• Stability: Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 3 months.
• CAS DataBase Reference: 5-[3-Methoxy-4-(4-methoxy-benzyloxy)-benzyl]-pyrimidine-2,4-diamine(CAS DataBase Reference)
• NIST Chemistry Reference: 5-[3-Methoxy-4-(4-methoxy-benzyloxy)-benzyl]-pyrimidine-2,4-diamine(870483-87-7)
• EPA Substance Registry System: 5-[3-Methoxy-4-(4-methoxy-benzyloxy)-benzyl]-pyrimidine-2,4-diamine(870483-87-7)

Safety Data

• Hazard Codes: Xn,Xi
• Statements: 22-36/37/38
• Safety Statements: 26-36/37/39
• WGK Germany: 3
• Hazardous Substances Data: 870483-87-7(Hazardous Substances Data)

Usage

Description

5-[3-Methoxy-4-(4-methoxy-benzyloxy)-benzyl]-pyrimidine-2,4-diamine, also known as GW-2580, is a potent and selective inhibitor of cFMS receptor kinase. It is a small molecule compound with the molecular formula C20H22N4O3 and a molecular weight of 366.42 g/mol. GW-2580 completely inhibits cFMS in vitro at 60 nM with no activity against 26 other kinases. It has been shown to inhibit bone degradation in human osteoclasts, rat calvaria, and fetal long bone, as well as LPS-induced TNF production in mice. Additionally, GW-2580 abrogates infiltration of macrophages into synovial joints of arthritic mice and is active in vivo.

Uses

Used in Pharmaceutical Industry:
5-[3-Methoxy-4-(4-methoxy-benzyloxy)-benzyl]-pyrimidine-2,4-diamine is used as a research compound for studying its effect on paracrine signaling from stretched cardiomyocyte on cardiac fibroblast phenotype. This helps in understanding the role of cFMS receptor kinase in various biological processes and its potential as a therapeutic target for treating related diseases.
Used in Research Applications:
5-[3-Methoxy-4-(4-methoxy-benzyloxy)-benzyl]-pyrimidine-2,4-diamine is used as a research tool for investigating the role of cFMS receptor kinase in various cellular processes, including cell growth, differentiation, and migration. It can be used to study the effects of inhibiting cFMS receptor kinase on these processes and its potential implications in disease treatment and prevention.
Used in Drug Discovery:
5-[3-Methoxy-4-(4-methoxy-benzyloxy)-benzyl]-pyrimidine-2,4-diamine is used as a lead compound in drug discovery for the development of new therapeutic agents targeting cFMS receptor kinase. Its potent and selective inhibitory activity makes it a valuable starting point for designing and optimizing new drugs with improved efficacy and safety profiles.
Used in Preclinical Studies:
5-[3-Methoxy-4-(4-methoxy-benzyloxy)-benzyl]-pyrimidine-2,4-diamine is used in preclinical studies to evaluate its potential as a therapeutic agent for treating diseases associated with cFMS receptor kinase activity. These studies can provide valuable insights into its pharmacological properties, safety, and efficacy, which can guide further development and optimization of this compound for clinical use.
Used in Target Validation:
5-[3-Methoxy-4-(4-methoxy-benzyloxy)-benzyl]-pyrimidine-2,4-diamine is used for validating cFMS receptor kinase as a therapeutic target in various disease models. By studying the effects of inhibiting this kinase, researchers can gain a better understanding of its role in disease pathogenesis and its potential as a target for developing new treatments.

Biochem/physiol Actions

GW2580 is a cell-permeable, potent and selective ATP-competitive inhibitor of cFMS kinase, receptor for macrophage-colony stimulating factor, M-CSF or CSF-1, and a key regulator of macrophage and osteoclast activation and differentiation. FMS is a type III receptor tyrosine kinase that binds to the macrophage or monocyte colony-stimulating factor (M-CSF or CSF-1). Overexpression of CSF-1 and/or FMS has been implicated in a number of disease states including the growth of metastasis of some types of cancer, in promoting osteoclast proliferation in bone osteolysis, and in several inflammatory disorders. GW2580 selectively inhibits cFMS-mediated cellular functions in vitro at 0.06 μM as well as CSF-1-dependent tumor growth in vivo. GW2580 was inactive against 26 other kinases.

References

1) Conway et al. (2005), Inhibition of colony-stimulating-factor-1 signaling in vivo with the orally bioavailable cFMS kinase inhibitor GW2580; Proc. Natl. Acad. Sci. USA, 102 16078 2) Paniagua et al. (2010), c-Fms-mediated differentiation and priming of monocyte lineage cells play a central role in autoimmune arthritis; Arthritis Res. Ther., 12 R32