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| 5mg |
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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.
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| 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].
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| 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].
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| 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. |
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| 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. |
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| 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. |
| Molecular Formula |
C21H15CL2FN4O
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|---|---|
| Molecular Weight |
429.27
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| Exact Mass |
428.061
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| CAS # |
287204-45-9
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| PubChem CID |
5311104
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
4.915
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
29
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| Complexity |
640
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
SLCFEJAMCRLYRG-UHFFFAOYSA-N
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| 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)
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| Chemical Name |
6-(2,6-dichlorophenyl)-2-(4-fluoro-3-methylanilino)-8-methylpyrido[2,3-d]pyrimidin-7-one
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| Synonyms |
PD180970 PD180970 PD180970
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~232.95 mM)
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| 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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