PD 180970

PD180970 is a highly potent and ATP-competitive p210Bcr-Abl kinase inhibitor, with an IC50 of 5 nM for inhibiting the autophosphorylation of p210Bcr-Abl. PD180970 also inhibits Src and KIT kinase with IC50s 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].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> Src

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> Bcr-Abl

Research Areas >> Neurological Disease

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> c-Kit

Bcr-Abl:5 nM (IC50, p210Bcr-Abl kinase)

Src:0.8 nM (IC50)

KIT:50 nM (IC50)

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 p210Bcr-Abl (IC50 of 5 nM) and the kinase activity of purified recombinant Abl tyrosine kinase (IC50 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 IC50 of 5 nM[2]. 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.

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: 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.

[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.