PRT-060318

Research use only, not for human use.

PRT-060318 (PRT318) is a novel selective inhibitor of the Syk tyrosine kinase, as an approach to HIT treatment.

PRT-060318, also known as PRT318 or P142–76, is a novel selective inhibitor of the tyrosine kinase Syk, as an approach to HIT treatment. PRT318 completely inhibited HIT immune complex-induced aggregation of both human and transgenic HIT mouse platelets. Transgenic HIT model mice were treated with KKO, a mouse monoclonal HIT-like antibody, and heparin. The experimental group received orally dosed PRT318, whereas the control group received vehicle. Nadir platelet counts of PRT318-treated mice were significantly higher than those of control mice. When examined with a novel thrombosis visualization technique, mice treated with PRT318 had significantly reduced thrombosis.

PRT318 is a potent inhibitor of purified Syk kinase with an IC50 of 4 nM. Syk kinase is inhibited by 92%, whereas all other kinases retains more than 70% at a concentration of 50 nM of PRT318. PRT318 and P505-15 effectively antagonize CLL cell survival after B-cell receptor (BCR) triggering and in nurse-like cell-co-cultures. They inhibit BCR-dependent secretion of the chemokines CCL3 and CCL4 by CLL cells, and leukemia cell migration toward the tissue homing chemokines CXCL12, CXCL13, and beneath stromal cells. PRT318 and P505-15 inhibit Syk and extracellular signal-regulated kinase phosphorylation after BCR triggering.

PRT318 completely inhibits HIT immune complex-induced aggregation of both human and transgenic HIT mouse platelets. Pretreatment of mice with PRT318 markedly reduces HIT IC-induced thrombosis in the lungs. The Thrombosis Score is significantly lower for PRT318-treated mice compared with control.

PRT060318 | PRT 060318 | PRT-060318 | PRT318

PI3K/Akt/mTOR signaling

mTOR

Syk

Cancer|Inflammation/Immunology

——

1194961-19-7

449.81

C18H24N6O·3HCl

>98% (HPLC)

H2O : 5.6 mg/mL. 16.45 mM;

CC1=CC(=CC=C1)NC2=NC(=NC=C2C(=O)N)N[C@@H]3CCCC[C@@H]3N

2-(((1R,2S)-2-aminocyclohexyl)amino)-4-(m-tolylamino)pyrimidine-5-carboxamide

(-20℃)

With Ice Pack

≥ 2 years