1194961-19-7

Basic information

• Product Name: PRT-060318
• Synonyms: PRT-060318;PRT-060318(PRT318);2-[[(1R,2S)-2-Aminocyclohexyl]amino]-4-[(3-methylphenyl)amino]-5-pyrimidinecarboxamide;P 142-76;PRT 318
• CAS NO: 1194961-19-7
• Molecular Formula: C18H24N6O
• Molecular Weight: 340.42276
• Mol File: 1194961-19-7.mol
• Article Data: 0

Chemical Properties

• Boiling Point: 602.1±65.0 °C(Predicted)
• Appearance: /
• Density: 1.277±0.06 g/cm3(Predicted)
• Storage Temp.: Refrigerator, under inert atmosphere
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 14.10±0.50(Predicted)
• CAS DataBase Reference: PRT-060318(CAS DataBase Reference)
• NIST Chemistry Reference: PRT-060318(1194961-19-7)
• EPA Substance Registry System: PRT-060318(1194961-19-7)

Safety Data

• Hazardous Substances Data: 1194961-19-7(Hazardous Substances Data)

Usage

Description

PRT-060318 is a potent and selective inhibitor of spleen tyrosine kinase (Syk) with an IC50 of 4 nM. It demonstrates high selectivity, inhibiting 92% of Syk activity while allowing other kinases to retain over 70% activity at a concentration of 50 nM in a panel of 270 kinases. PRT-060318 is effective in inducing chronic lymphocytic leukemia (CLL) B cell apoptosis, inhibiting the secretion of chemokines CCL3, CCL4, and CXCL13, and preventing CLL B cell chemotaxis and pseudoemperipolesis.

Uses

Used in Heparin-Induced Thrombocytopenia (HIT) Treatment:
PRT-060318 is used as a novel selective inhibitor of the tyrosine kinase Syk for the treatment of Heparin-Induced Thrombocytopenia (HIT), a major cause of morbidity and mortality. It prevents thrombosis in a transgenic mouse model of HIT and inhibits convulxin-induced aggregation of human platelet-rich plasma with an IC50 of 2.5 μM.
Used in Chronic Lymphocytic Leukemia (CLL) Therapy:
In the field of oncology, PRT-060318 is used as a therapeutic agent for Chronic Lymphocytic Leukemia (CLL). It induces CLL B cell apoptosis, inhibits the secretion of chemokines CCL3, CCL4, and CXCL13, and prevents CLL B cell chemotaxis and pseudoemperipolesis, offering a potential treatment option for patients with this condition.

in vitro

prt-060318 was identified as a potent inhibitor of purified syk kinase. syk kinase was inhibited by 92%, while the activities all other kinases retained more than 70% when prt-060318 were evaluated at a concentration of 50 nm in a broad panel of kinase enzyme assays. in addition, prt-060318 could dose-responsively inhibited convulxin-induced human prp aggregation. moreover, it was found that prt-060318 was able to dose-responsively inhibit the increases in intracellular calcium in convulxin-treated platelets [1].

in vivo

animal study showed that in contrast to vehicle-treated mice developed the expected thrombocytopenia, prt-060318-treated mice had no significant change in platelet counts after injection of heparin. moreover, the nadir platelet counts of prt-060318-treated mice were found to be significantly higher than control mice. the prt-060318-treated mice showed no bleeding diathesis or other adverse effects. in addition, prt-060318 treatment in crush thrombosis model resulted in significant inhibition of platelet deposition without changing bleeding time [1].

IC 50

4 nm

references

[1] reilly mp,sinha u,andré p,taylor sm,pak y,deguzman fr,nanda n,pandey a,stolla m,bergmeier w,mckenzie se. prt-060318, a novel syk inhibitor, prevents heparin-induced thrombocytopenia and thrombosis in a transgenic mouse model. blood.2011 feb 17;117(7):2241-6.