PPADS tetrasodium salt

Names

[ CAS No. ]:
192575-19-2

[ Name ]:
PPADS tetrasodium salt

[Synonym ]:
Tetrasodium 4-[(E)-{4-formyl-5-hydroxy-6-methyl-3-[(phosphonatooxy)methyl]pyridin-2-yl}diazenyl]benzene-1,3-disulfonate
Tetrasodium 4-[(E)-{4-formyl-5-hydroxy-6-methyl-3-[(phosphonatooxy)methyl]-2-pyridinyl}diazenyl]-1,3-benzenedisulfonate
PPADS (sodium salt)
1,3-Benzenedisulfonic acid, 4-[(E)-2-[4-formyl-5-hydroxy-6-methyl-3-[(phosphonooxy)methyl]-2-pyridinyl]diazenyl]-, sodium salt (1:4)
MFCD11046026

Biological Activity

[Description]:

PPADS tetrasodiuma is a non-selective P2X receptor antagonist. PPADS tetrasodiuma blocks recombinant P2X1, -2, -3, -5 with IC50s ranging from 1 to 2.6 μM. PPADS tetrasodiuma blocks native P2Y2-like (IC50~0.9 mM) and recombinant P2Y4 (IC50~15 mM) receptors. PPADS tetrasodiuma is an inhibitor of the reverse mode of the Na/Ca²⁺exchanger in guinea pig airway smooth muscle[1][2].

[Related Catalog]:

Signaling Pathways >> Membrane Transporter/Ion Channel >> P2X Receptor

Research Areas >> Neurological Disease

[In Vitro]

PPADS tetrasodiuma (1-30 μM; 10-50 minutes) inhibits Na+/Ca2+ exchanger reverse mode (NCXREV) in a time- and concentration dependent manner[2]. PPADS tetrasodiuma is effective at other native and recombinant P2XRs. At human P2XRs sensitivity to PPADS tetrasodiuma depended on the subtype and was highest at the hP2X1, -2, -3, -5, and -7Rs with an IC50 of ∼1–3 and ∼30 μM for the hP2X4R[3].

[In Vivo]

PPADS tetrasodiuma (15-60 mg/100g body weight (BW); i.p.; every 12 hours for 8 days) inhibits glomerular mesangial cells (MC) proliferation without altering proliferation of non-MC in vivo in mesangial proliferative glomerulonephritis[4]. Animal Model: Male Sprague-Dawley ratsweighing 160 to 200 g (anti-Thy1 disease mode)[4] Dosage: 15 mg/100g BW, 30 mg/100g BW, 60 mg/100g BW Administration: i.p.; every 12 hours for 8 days (the first PPADS injection was administered 60 minutes after disease induction, and the loading dose always contained double the amount of PPADS compared to the following injections.) Result: Specifically and dose-dependently reduced early (day 3) glomerular mesangial cell proliferation without altering proliferation of non-MC.

[References]

[1]. Flores-Soto E, et al. PPADS, a P2X receptor antagonist, as a novel inhibitor of the reverse mode of the Na⁺/Ca²⁺ exchanger in guinea pig airway smooth muscle. Eur J Pharmacol. 2012 Jan 15;674(2-3):439-44.

[2]. Huo H, et al. Mapping the binding site of the P2X receptor antagonist PPADS reveals the importance of orthosteric site charge and the cysteine-rich head region. J Biol Chem. 2018 Aug 17;293(33):12820-12831.

[3]. Einfluss von ATP und seinen Derivaten auf die Aktivierung von Monozyten.

[4]. Rost S, et al. P2 receptor antagonist PPADS inhibits mesangial cell proliferation in experimental mesangialproliferative glomerulonephritis. Kidney Int. 2002 Nov;62(5):1659-71.