[CAS NO. 287204-45-9] PD180970
PRODUCTS SPECIFICATIONS [287204-45-9]
DESCRIPTION [287204-45-9]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 429.27 |
| Molecular Formula | C21H15Cl2FN4O |
| SMILES | O=C1C(C2=C(Cl)C=CC=C2Cl)=CC3=CN=C(NC4=CC=C(F)C(C)=C4)N=C3N1C |
Summary
PD180970 is a highly potent and ATP-competitive p210 Bcr-Abl kinase inhibitor, with an IC 50 of 5 nM for inhibiting the autophosphorylation of p210 Bcr-Abl . PD180970 also inhibits Src and KIT kinase with IC 50 s of 0.8 nM and 50 nM, respectively. PD180970 indcues apoptosis of K562 leukemic cells, and can be used for chronic myelogenous leukemia research [1] [2] [3] .
IC50 & Target
|
Bcr-Abl 5 nM (IC 50 , p210 Bcr-Abl kinase) |
Src 0.8 nM (IC 50 ) |
KIT 50 nM (IC 50 ) |
In Vitro
PD180970 (0.5 μM; 24-96 hours) treatment causes cell death K562 cells
[1]
.
PD180970 (0.5 μM; 24-48 hours) treatment induces apoptosis of K562 cells. The result shows increase in annexin V-PI double-positive cells
[1]
.
PD180970 inhibits tyrosine phosphorylation of p210Bcr-Abl, Gab2, and CrkL in K562 cells with IC50 values of 170 nM, 80 nM, and 80 nM, respectively. In vitro, PD180970 potently inhibits autophosphorylation of p210
Bcr-Abl
(IC
50
of 5 nM) and the kinase activity of purified recombinant Abl tyrosine kinase (IC
50
of 2.2 nM)
[1]
.
The blocking Bcr-Abl kinase activity using PD180970 in the human K562 CML cell line resulted in inhibition of Stat5 DNA-binding activity with an IC
50
of 5 nM
[2]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Viability Assay [1]
| Cell Line: | K562 cells |
| Concentration: | 0.5 μM |
| Incubation Time: | 24 hours, 48 hours, 72 hours, 96 hours |
| Result: | Resulted in cell death. |
Apoptosis Analysis [1]
| Cell Line: | K562 cells |
| Concentration: | 0.5 μM |
| Incubation Time: | 24 hours, 48 hours |
| Result: | Increased annexin V-positive/PI-negative cells. |
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] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | Male C57BL/6J mice (3-4 months old) injected with MPTP [4] |
| Dosage: | 5 mg/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. |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 125 mg/mL ( 291.19 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 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 |
-
1.
Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 2.08 mg/mL (4.85 mM); Clear solution
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.