PRT062607(P505-15,BIIB057)HCl

Molecular Weight (MW)	429.91
Formula	C19H23N9O.HCl
CAS No.	1370261-97-4 (HCl);
Storage	-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)	DMSO: 86 mg/mL (200.0 mM)
Water: <1 mg/mL
Ethanol: 86 mg/mL (200.0 mM)
Solubility (In vivo)	Saline: 30 mg/mL
Synonyms	P505-15; P-50515; PRT2607; PRT062607; P50515; BIIB057; PRT-062607; PRT 062607; PRT-2607; PRT 2607; P-505-15; P 505-15; P 50515; BIIB-057; BIIB 057. Chemical Name: 4-((3-(2H-1,2,3-triazol-2-yl)phenyl)amino)-2-(((1R,2S)-2-aminocyclohexyl)amino)pyrimidine-5-carboxamide hydrochloride SMILES Code: O=C(C1=CN=C(N[C@H]2[C@@H](N)CCCC2)N=C1NC3=CC=CC(N4N=CC=N4)=C3)N.[H]Cl

Molecular Weight (MW)

429.91

Formula

C19H23N9O.HCl

CAS No.

1370261-97-4 (HCl);

Storage

-20℃ for 3 years in powder form

-80℃ for 2 years in solvent

Solubility (In vitro)

DMSO: 86 mg/mL (200.0 mM)

Water: <1 mg/mL

Ethanol: 86 mg/mL (200.0 mM)

Solubility (In vivo)

Saline: 30 mg/mL

Synonyms

P505-15; P-50515; PRT2607; PRT062607; P50515; BIIB057; PRT-062607; PRT 062607; PRT-2607; PRT 2607; P-505-15; P 505-15; P 50515; BIIB-057; BIIB 057.

Chemical Name: 4-((3-(2H-1,2,3-triazol-2-yl)phenyl)amino)-2-(((1R,2S)-2-aminocyclohexyl)amino)pyrimidine-5-carboxamide hydrochloride

SMILES Code: O=C(C1=CN=C(N[C@H]2[C@@H](N)CCCC2)N=C1NC3=CC=CC(N4N=CC=N4)=C3)N.[H]Cl

In Vitro	In vitro activity: PRT062607(P505-15) anti-SYK activity is at least 80-fold greater than its affinity for other kinases. at least 80-fold greater than its affinity for other kinases. PRT062607 potently inhibits B cell antigen receptor-mediated B cell signaling and activation (IC50 0.27 and 0.28 μM, respectively) and Fcε receptor 1-mediated basophil degranulation (IC50 0.15 μM). PRT062607 inhibits 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. PRT062607 furthermore inhibits Syk and extracellular signal-regulated kinase phosphorylation after BCR triggering Kinase Assay: The extent of substrate phosphorylation by Syk is measured in the presence of various PRT062607 concentrations. Syk activity is determined by a fluorescent antibody specific for phosphorylated tyrosine by using the increase of FRET. Twelve concentrations are tested for dose response. Specificity and potency of kinase inhibition is determined by evaluation of PRT062607 in the Millipore KinaseProfiler panel of 270 independent purified kinase assays. For profiling, PRT062607 is tested in duplicate at two concentrations at a fixed concentration of ATP. Subsequently, IC50 determinations using the radioactive assays are carried out at an ATP concentration optimized for each individual kinase. All radioactive ATP incorporation enzyme assays are performed at Millipore. Cell Assay: To compare the relative sensitivity of primary versus tumor B-cells, the mixing experiments in which SU-DHL6 was combined with human whole blood and treated with P505-15 were performed. Under these conditions, whereas the tumor B-cell line underwent apoptosis in response to SYK inhibition, primary B-cells did not.
In Vivo	The pharmacokinetic/pharmacodynamic relationship predicted that 70% Syk suppression is maintained in mice over a 24h period after 30 mg/kg dosing. At 15 mg/kg, Syk inhibition ranges from 7.5% (Cmin) to 78.4% (Cmax) with an average inhibition of 67% over 24 h. Oral administration of PRT062607 produced dose-dependent anti-inflammatory activity in two rodent models of rheumatoid arthritis. Statistically significant efficacy is observed at concentrations that specifically suppressed Syk activity by 67%
Animal model	NOD/SCID mice injected with Ramos cells
Formulation & Dosage	10, 15, or 20 mg/kg; Oral administration
References	J Pharmacol Exp Ther. 2012 Feb;340(2):350-9; Leukemia. 2012 Jul;26(7):1576-83.

In Vitro

In vitro activity: PRT062607(P505-15) anti-SYK activity is at least 80-fold greater than its affinity for other kinases. at least 80-fold greater than its affinity for other kinases. PRT062607 potently inhibits B cell antigen receptor-mediated B cell signaling and activation (IC50 0.27 and 0.28 μM, respectively) and Fcε receptor 1-mediated basophil degranulation (IC50 0.15 μM). PRT062607 inhibits 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. PRT062607 furthermore inhibits Syk and extracellular signal-regulated kinase phosphorylation after BCR triggering

Kinase Assay: The extent of substrate phosphorylation by Syk is measured in the presence of various PRT062607 concentrations. Syk activity is determined by a fluorescent antibody specific for phosphorylated tyrosine by using the increase of FRET. Twelve concentrations are tested for dose response. Specificity and potency of kinase inhibition is determined by evaluation of PRT062607 in the Millipore KinaseProfiler panel of 270 independent purified kinase assays. For profiling, PRT062607 is tested in duplicate at two concentrations at a fixed concentration of ATP. Subsequently, IC50 determinations using the radioactive assays are carried out at an ATP concentration optimized for each individual kinase. All radioactive ATP incorporation enzyme assays are performed at Millipore.

Cell Assay: To compare the relative sensitivity of primary versus tumor B-cells, the mixing experiments in which SU-DHL6 was combined with human whole blood and treated with P505-15 were performed. Under these conditions, whereas the tumor B-cell line underwent apoptosis in response to SYK inhibition, primary B-cells did not.

In Vivo

The pharmacokinetic/pharmacodynamic relationship predicted that 70% Syk suppression is maintained in mice over a 24h period after 30 mg/kg dosing. At 15 mg/kg, Syk inhibition ranges from 7.5% (Cmin) to 78.4% (Cmax) with an average inhibition of 67% over 24 h. Oral administration of PRT062607 produced dose-dependent anti-inflammatory activity in two rodent models of rheumatoid arthritis. Statistically significant efficacy is observed at concentrations that specifically suppressed Syk activity by 67%

Animal model

NOD/SCID mice injected with Ramos cells

Formulation & Dosage

10, 15, or 20 mg/kg; Oral administration

References

J Pharmacol Exp Ther. 2012 Feb;340(2):350-9; Leukemia. 2012 Jul;26(7):1576-83.

CAS NO:	1370261-97-4
规格:	≥98%

包装	价格(元)
1mg	电议
2mg	电议
5mg	电议
10mg	电议
25mg	电议
50mg	电议
100mg	电议
250mg	电议
500mg	电议