6-(2,6-Dichloro-phenyl)-2-(4-fluoro-3-methyl-phenylamino)-8-methyl-8H-pyrido[2,3-d]pyrimidin-7-one

Product Name6-(2,6-Dichloro-phenyl)-2-(4-fluoro-3-methyl-phenylamino)-8-methyl-8H-pyrido[2,3-d]pyrimidin-7-one
CAS287204-45-9
MFC21H15Cl2FN4O
MW429.27
EINECS
MOL File287204-45-9.mol

Chemical Properties

Boiling point	590.6±60.0 °C(Predicted)
Density	1.449±0.06 g/cm3(Predicted)
storage temp.	2-8°C
solubility	DMSO: >20mg/mL
pka	3.02±0.20(Predicted)
form	A solid
color	yellow
InChI	1S/C21H15Cl2FN4O/c1-11-8-13(6-7-17(11)24)26-21-25-10-12-9-14(20(29)28(2)19(12)27-21)18-15(22)4-3-5-16(18)23/h3-10H,1-2H3,(H,25,26,27)
InChIKey	SLCFEJAMCRLYRG-UHFFFAOYSA-N
SMILES	CN1C(=O)C(=Cc2cnc(Nc3ccc(F)c(C)c3)nc12)c4c(Cl)cccc4Cl

Safety Information

Hazard Codes	T
Risk Statements	25
Safety Statements	45
RIDADR	UN 2811 6.1 / PGIII
WGK Germany	3
Storage Class	6.1C - Combustible acute toxic Cat.3 toxic compounds or compounds which causing chronic effects
Hazard Classifications	Acute Tox. 3 Oral Aquatic Chronic 4

Usage And Synthesis

Uses

PD 180970 is an ATP-competitive inhibitor of p210 tyrosine kinase which selectively induces apoptosis in chronic myeloid leukemia (CML) K562 cells.

Biological Activity

PD-180970 is a potent inhibitor of the p210 Bcr-Abl tyrosine kinase.

Enzyme inhibitor

This pyridopyrimidine (FWfree-base = 429.28 g/mol) inhibits Bcr-Abl proteintyrosine kinase and induces apoptosis of K562 leukemic cells. In vitro, PD180970 potently inhibited p210Bcr-Abl autophosphorylation (IC50 = 5 nM) as well as the kinase activity of purified Abl tyrosine kinase (IC50 = 2.2 nM). Incubation of K562 cells with PD180970 resulted in cell death, with results of nuclear staining, apoptotic-specific poly(ADP-ribose) polymerase cleavage, and annexin V binding assays confirming as much. Significantly, PD180970 is without effect on the growth and viability of p210Bcr-Ablnegative HL60 human leukemic cells. Such findings demonstrate that PD180970 is among the most potent known inhibitors of the p210Bcr-Abl tyrosine kinase and that it is a promising candidate as a novel therapeutic agent for Bcr-Abl-positive leukemia

in vivo

PD180970 (5 mg/kg; intraperitonial injection; daily; for 7 days) mitigates MPTP-induced neuronal loss in mice. PD180970 has the neuroprotective ability in a preclinical mouse model of Parkinson's disease (PD)^[4].

Animal Model:	Male C57BL/6J mice (3-4 months old) injected with MPTP^[4]
Dosage:	5mg/kg
Administration:	Intraperitonial injection; daily; for 7 days
Result:	Decreased number of activated microglia on activation by MPTP in mice brains. And showed significant reduction in intensity of Iba1 expression in activated microglia.

IC 50

Bcr-Abl: 5 nM (IC₅₀, p210^Bcr-Abl kinase); Src: 0.8 nM (IC₅₀); KIT: 50 nM (IC₅₀)

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