PRT-060318

• CAT Number: R034971
• CAS Number: 1194961-19-7
• Molecular Formula: C18H24N6O
• Molecular Weight: 340.431
• Purity: ≥95%
• Synonyms: 2-[[(1R,2S)-2-Aminocyclohexyl]amino]-4-[(3-methylphenyl)amino]-5-pyrimidinecarboxamide; P 142-76; PRT 318
• Target: Syk
• Solubility: Soluble in DMSO
• Storage: Store at -20°C
• IUPAC Name: 2-[[(1R,2S)-2-aminocyclohexyl]amino]-4-(3-methylanilino)pyrimidine-5-carboxamide
• InChI: InChI=1S/C18H24N6O/c1-11-5-4-6-12(9-11)22-17-13(16(20)25)10-21-18(24-17)23-15-8-3-2-7-14(15)19/h4-6,9-10,14-15H,2-3,7-8,19H2,1H3,(H2,20,25)(H2,21,22,23,24)/t14-,15+/m0/s1
• InChIKey: NZNTWOVDIXCHHS-LSDHHAIUSA-N
• SMILES: CC1=CC(=CC=C1)NC2=NC(=NC=C2C(=O)N)NC3CCCCC3N

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.

Reference

1:Blood. 2011 Feb 17;117(7):2241-6. doi: 10.1182/blood-2010-03-274969. Epub 2010 Nov 18. PRT-060318, a novel Syk inhibitor, prevents heparin-induced thrombocytopenia and thrombosis in a transgenic mouse model.Reilly MP,Sinha U,André P,Taylor SM,Pak Y,Deguzman FR,Nanda N,Pandey A,Stolla M,Bergmeier W,McKenzie SE, PMID: 21088136 PMCID: PMC3568699 DOI: 10.1182/blood-2010-03-274969 Abstract: Heparin-induced thrombocytopenia (HIT) is a major cause of morbidity and mortality resulting from the associated thrombosis. Extensive studies using our transgenic mouse model of HIT have shown that antibodies reactive with heparin-platelet factor 4 complexes lead to FcγRIIA-mediated platelet activation in vitro as well as thrombocytopenia and thrombosis in vivo. We tested PRT-060318 (PRT318), 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. The Syk inhibitor PRT318 thus prevented both HIT immune complex-induced thrombocytopenia and thrombosis in vivo, demonstrating its activity in HIT.