PD 151746 is a selective calpain-1 inhibitor with an IC50 of 260 nM. PD 151746 binds μ-calpain Ca 2+ -binding sites, and shows selectivity over cathepsin B, papain, trypsin, thermolysin, and basal calcineurin. PD 151746 reduces Oxidized low-density lipoprotein (oxLDL)-induced cytotoxicity, apoptotic DNA fragmentation, and blocks IL-1α maturation. PD 151746 can be used for the research of atherosclerosis and psoriasis [1] [2] [3].
In Vivo, PD 151746 (10 mg; i.p.; single injection) significantly reduces epidermal thickness and decreases mature IL-1α and calpain-1 protein levels to ameliorate Imiquimod -induced psoriatic skin lesions in mice[3].
In Vitro, PD 151746 potently and selectively inhibits μ-calpain with an apparent Ki of 0.26 μM, shows 20-fold selectivity over m-calpain[1]. PD 151746 (10 μM; 2 h) effectively inhibits calpain activity in Maitotoxin-treated human neuroblastoma SH-SY5Y cells[1]. PD 151746 (2-20 μM; 24 h) dose-dependently reduces oxLDL-induced cytotoxicity in HMEC-1 cells[2]. PD 151746 (2-20 μM; 12 h) significantly reduces oxLDL-induced apoptotic nucleosomal DNA fragmentation in HMEC-1 cells at 20 μM[2]. PD 151746 (20 μM; 20 h) inhibits oxLDL-induced calpain-mediated cleavage of α-fodrin in HMEC-1 cells[2]. PD 151746 (20 μM; 20 h) inhibits oxLDL-induced calpain-mediated cleavage of Bid in HMEC-1 cells[2]. PD 151746 (15 μM) blocks hS100A7-induced mature IL-1α production in normal human epidermal keratinocytes, and it inhibits calpain-1 with an IC50 of 260 nM and 20-fold selectivity over calpain-2[3].
References:
[1]. Wang KK, et al. An alpha-mercaptoacrylic acid derivative is a selective nonpeptide cell-permeable calpain inhibitor and is neuroprotective. Proc Natl Acad Sci U S A. 1996;93(13):6687-6692.
[2]. Pörn-Ares MI, et al. Oxidized low-density lipoprotein induces calpain-dependent cell death and ubiquitination of caspase 3 in HMEC-1 endothelial cells. Biochem J. 2003 Sep 1;374(Pt 2):403-11.
[3]. Lei H, et al. Human S100A7 Induces Mature Interleukin1α Expression by RAGE-p38 MAPK-Calpain1 Pathway in Psoriasis. PLoS One. 2017;12(1):e0169788. Published 2017 Jan 6.
In Vivo, PD 151746 (10 mg; i.p.; single injection) significantly reduces epidermal thickness and decreases mature IL-1α and calpain-1 protein levels to ameliorate Imiquimod -induced psoriatic skin lesions in mice[3].
In Vitro, PD 151746 potently and selectively inhibits μ-calpain with an apparent Ki of 0.26 μM, shows 20-fold selectivity over m-calpain[1]. PD 151746 (10 μM; 2 h) effectively inhibits calpain activity in Maitotoxin-treated human neuroblastoma SH-SY5Y cells[1]. PD 151746 (2-20 μM; 24 h) dose-dependently reduces oxLDL-induced cytotoxicity in HMEC-1 cells[2]. PD 151746 (2-20 μM; 12 h) significantly reduces oxLDL-induced apoptotic nucleosomal DNA fragmentation in HMEC-1 cells at 20 μM[2]. PD 151746 (20 μM; 20 h) inhibits oxLDL-induced calpain-mediated cleavage of α-fodrin in HMEC-1 cells[2]. PD 151746 (20 μM; 20 h) inhibits oxLDL-induced calpain-mediated cleavage of Bid in HMEC-1 cells[2]. PD 151746 (15 μM) blocks hS100A7-induced mature IL-1α production in normal human epidermal keratinocytes, and it inhibits calpain-1 with an IC50 of 260 nM and 20-fold selectivity over calpain-2[3].
References:
[1]. Wang KK, et al. An alpha-mercaptoacrylic acid derivative is a selective nonpeptide cell-permeable calpain inhibitor and is neuroprotective. Proc Natl Acad Sci U S A. 1996;93(13):6687-6692.
[2]. Pörn-Ares MI, et al. Oxidized low-density lipoprotein induces calpain-dependent cell death and ubiquitination of caspase 3 in HMEC-1 endothelial cells. Biochem J. 2003 Sep 1;374(Pt 2):403-11.
[3]. Lei H, et al. Human S100A7 Induces Mature Interleukin1α Expression by RAGE-p38 MAPK-Calpain1 Pathway in Psoriasis. PLoS One. 2017;12(1):e0169788. Published 2017 Jan 6.