PD180970 (PD-180970) is a novel and potent Bcr-Abl inhbitor with anti-leukemia activity. It is an ATP-competitive p210Bcr-Abl kinase inhibitor (IC50 = 5 nM) that inhibiting the autophosphorylation of p210Bcr-Abl. PD180970 also inhibits Src and KIT kinase with IC50s of 0.8 nM and 50 nM, respectively.

Physicochemical Properties

Molecular Formula	C21H15CL2FN4O
Molecular Weight	429.27
Exact Mass	428.061
CAS #	287204-45-9
PubChem CID	5311104
Appearance	Light yellow to yellow solid powder
LogP	4.915
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	3
Heavy Atom Count	29
Complexity	640
Defined Atom Stereocenter Count	0
InChi Key	SLCFEJAMCRLYRG-UHFFFAOYSA-N
InChi Code	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)
Chemical Name	6-(2,6-dichlorophenyl)-2-(4-fluoro-3-methylanilino)-8-methylpyrido[2,3-d]pyrimidin-7-one
Synonyms	PD180970 PD180970 PD180970
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	Bcr-Abl:5 nM (IC50, p210Bcr-Abl kinase); Src:0.8 nM (IC50); KIT:50 nM (IC50)
ln Vitro	K562 cells are killed by PD180970 (0.5 μM; 24-96 hours) treatment[1]. Treatment with PD180970 (0.5 μM; 24-48 hours) causes K562 cells to undergo apoptosis. An increase in annexin V-PI double-positive cells is shown by the results [1]. PD180970 suppresses the kinase activity of pure recombinant Abl tyrosine kinase (IC50 of 2.2 nM) as well as the tyrosine phosphorylation of p210Bcr-Abl, Gab2, and CrkL in K562 cells (405 nM, 80 nM, and 80 nM, respectively). With an IC50 of 5 nM, the human K562 CML cell line's Bcr-Abl kinase activity was blocked using PD180970, which inhibited Stat5 DNA-binding activity[2].
ln Vivo	In mice, PD180970 (5 mg/kg; intraperitoneal injection; daily; for 7 days) reduces the loss of neurons caused by MPTP. According to a preclinical animal model of Parkinson's disease (PD), PD180970 possesses neuroprotective properties [4].
Cell Assay	Cell Viability Assay[1] Cell Types: K562 cells Tested Concentrations: 0.5 μM Incubation Duration: 24 hrs (hours), 48 hrs (hours), 72 hrs (hours), 96 hrs (hours) Experimental Results: Resulted in cell death. Apoptosis Analysis[1] Cell Types: K562 cells Tested Concentrations: 0.5 μM Incubation Duration: 24 hrs (hours), 48 hrs (hours) Experimental Results: Increased annexin V-positive/PI-negative cells.
Animal Protocol	Animal/Disease Models: Male C57BL /6J mice (3-4 months old) injected with MPTP[4] Doses: 5 mg/kg Route of Administration: Intraperitonial injection; daily; for 7 days Experimental Results: diminished number of activated microglia on activation by MPTP in mice brains. And demonstrated significant reduction in intensity of Iba1 expression in activated microglia.
References	[1]. J F Dorsey, et al. The pyrido[2,3-d]pyrimidine derivative PD180970 inhibits p210Bcr-Abl tyrosine kinase and induces apoptosis of K562 leukemic cells. Cancer Res. 2000 Jun 15;60(12):3127-31. [2]. Mei Huang, et al. Inhibition of Bcr-Abl kinase activity by PD180970 blocks constitutive activation of Stat5 and growth of CML cells. Oncogene. 2002 Dec 12;21(57):8804-16. [3]. Amie S Corbin, et al. Sensitivity of oncogenic KIT mutants to the kinase inhibitors MLN518 and PD180970. Blood. 2004 Dec 1;104(12):3754-7. [4]. Suresh Sn, et al. Small molecule modulator of aggrephagy regulates neuroinflammation to curb pathogenesis of neurodegeneration. EBioMedicine. 2019 Dec;50:260-273.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~232.95 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 1.25 mg/mL (2.91 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.3295 mL	11.6477 mL	23.2954 mL
	5 mM	0.4659 mL	2.3295 mL	4.6591 mL
	10 mM	0.2330 mL	1.1648 mL	2.3295 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.