219580-11-7

Basic information

• Product Name: PD 173074
• Synonyms: n-[2-[[4-(diethylamino)butyl]amino-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl]-n'-(1,1-dimethylethyl)urea;N-[2-[[4-(diethylaMino)butyl]aMino]-6-(3,5-diMethoxyphenyl)pyrido[2,3-d ]pyriMidin-7-yl]-N'-(1,1-diMethylethyl)-;PD173074/PD-173074;1-(tert-butyl)-3-(2-((4-(diethylaMino)butyl)aMino)-6-(3,5-diMethoxyphenyl)pyrido[2,3-d]pyriMidin-7-yl)urea;1-(tert-Butyl)-3-(2-((4-(diethylamino)butyl)amino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-;Urea, N-[2-[[4-(diethylaMino)butyl]aMino]-6-(3,5-diMethoxyphenyl)pyrido[2,3-d]pyriMidin-7-yl]-N'-(1,1-diMethylethyl)-;PD176074;N-[2-[[4-(Diethylamino)butyl]amino]-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl]-N'-(1,1-dimethylethyl)urea PD 173074
• CAS NO: 219580-11-7
• Molecular Formula: C28H41N7O3
• Molecular Weight: 523.678
• Product Categories: Aromatics;Bases & Related Reagents;Heterocycles;Inhibitors;Intermediates & Fine Chemicals;Nucleotides;Pharmaceuticals;API;Antineoplastic
• Mol File: 219580-11-7.mol
• Article Data: 0

Chemical Properties

• Melting Point: 82-85°C
• Appearance: yellow/solid
• Density: 1.163
• Refractive Index: 1.598
• Storage Temp.: 2-8°C
• Solubility: DMSO: 21 mg/mL
• PKA: 10.12±0.43(Predicted)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 3 months.
• CAS DataBase Reference: PD 173074(CAS DataBase Reference)
• NIST Chemistry Reference: PD 173074(219580-11-7)
• EPA Substance Registry System: PD 173074(219580-11-7)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26
• WGK Germany: 3
• Hazardous Substances Data: 219580-11-7(Hazardous Substances Data)

Usage

Description

PD 173074 is a potent FGFR1 inhibitor with an IC50 of approximately 25 nM and also inhibits VEGFR2 with an IC50 of 100-200 nM. It is a member of the class of ureas that is 1-tert-butylurea, with a pyrido[2,3-d]pyrimidin-7-yl group substituted at position 3 and a 3,5-dimethoxyphenyl group at position 5. PD 173074 is an inhibitor of FGFR tyrosine kinase and, to a lesser extent, VEGFR1. It promotes stem cell self-renewal and is a yellow solid.

Uses

Used in Pharmaceutical Industry:
PD 173074 is used as a potent FGFR1 inhibitor for targeting cancer cells with overactive FGFR1, which is implicated in various cancers. Its ability to inhibit FGFR1 makes it a potential therapeutic agent for cancer treatment.
Used in Angiogenesis Inhibition:
PD 173074 is used as an inhibitor of VEGFR2, which plays a crucial role in angiogenesis, the formation of new blood vessels. By inhibiting VEGFR2, PD 173074 can help prevent the growth of new blood vessels that supply nutrients to tumors, thereby limiting their growth and spread.
Used in Stem Cell Research:
PD 173074 is used as a promoter of stem cell self-renewal, which is essential for maintaining the stem cell pool and their potential use in regenerative medicine and tissue repair.
Used in Biochemical Research:
PD 173074 is used as a research tool to study the role of FGFR and VEGFR in various biological processes, including cell proliferation, differentiation, and migration. Its use in research helps to advance our understanding of these pathways and their potential as therapeutic targets.

Biological Activity

Selective FGFR1 and FGFR3 inhibitor (IC 50 values are 5, 21.5, ~100, 17600 and 19800 nM for FGFR3, FGFR1, VEGFR2, PDGFR and c-Src respectively, and > 50000 nM for EGFR, InsR, MEK and PKC). Inhibits VEGF- and FGF-induced angiogenesis in the mouse cornea model of angiogenesis. Inhibits proliferation and differentiation of oligodendrocyte progenitors.

Biochem/physiol Actions

PD 173074 is a fibroblast growth factor receptor 3 (FGFR3) inhibitor: IC50 = 5 nM inhibition of FGFR3 autophosphorylation. PD 173074 arrests the G0/G1 phase of FGFR3-expressing cells. It is 100-fold more selective for FGFR3 than for VEGF receptors, IGF-1 receptors, and MAPKs.

in vitro

pd173074 was found to block h-510 and h-69 sclc proliferation and clonogenic growth in a dose-dependent fashion and prevent fgf-2-induced chemoresistance as well. these effects correlate with the inhibition of both fgfr1 and fgfr2 transphosphorylation. in addition, pd173074 showed a high degree of selectivity for fgfr tyrosine kinase [2].

in vivo

in the h-510 xenograft mouse model, tumor growth was significanlty improved similar to that seen with single-agent cisplatin administration. accordingly, pd173074 treatment resulted in significanlty prolonged median survival when compared with that of control sham-treated animals. more dramatically, pd173074 also induced complete responses lasting >6 months in 50% of in mice h-69 xenografts [2].

References

1 Bansal?et al. (2003),?Specific inhibitor of FGF receptor signaling: FGF-2 mediated effects on proliferation, differentiation and MAPK activation are inhibited by PD173074 in oligodendrocyte-lineage cells; J. Neurosci. Res.,?74?486 2) Kim?et al. (2012),?Regulation of autocrine fibroblast growth factor-2 signaling by perfusion flow in 3D human mesenchymal stem cell constructs; Biotechnol. Prog.,?28?1384 3) Zaragosi?et al. (2006),?Autocrine fibroblast growth factor 2 signaling is critical for self renewal of human multipotent adipose-derived stem cells; Stem Cells,?24?2412

InChI:InChI=1/C28H41N7O3/c1-8-35(9-2)13-11-10-12-29-26-30-18-20-16-23(19-14-21(37-6)17-22(15-19)38-7)25(31-24(20)32-26)33-27(36)34-28(3,4)5/h14-18H,8-13H2,1-7H3,(H3,29,30,31,32,33,34,36)