Peficitinib(ASP-015K,JNJ-54781532)

Molecular Weight (MW)	326.39
Formula	C18H22N4O2
CAS No.	944118-01-8 (free base);
Storage	-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)	DMSO: 65 mg/mL (199.1 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)	Chemical Name: 4-(((1R,2r,3S,5s,7s)-5-hydroxyadamantan-2-yl)amino)-1H-pyrrolo[2,3-b]pyridine-5-carboxamide SMILES Code: O=C(C1=CN=C(NC=C2)C2=C1N[C@H]3[C@]4([H])C[C@@]5([H])C[C@](C4)(O)C[C@]3([H])C5)N
Synonyms	JNJ54781532; JNJ54781532; JNJ 54781532; ASP015K; ASP015K; ASP 015K; Peficitinib;

Molecular Weight (MW)

326.39

Formula

C18H22N4O2

CAS No.

944118-01-8 (free base);

Storage

-20℃ for 3 years in powder form

-80℃ for 2 years in solvent

Solubility (In vitro)

DMSO: 65 mg/mL (199.1 mM)

Water: <1 mg/mL

Ethanol: <1 mg/mL

Solubility (In vivo)

Chemical Name: 4-(((1R,2r,3S,5s,7s)-5-hydroxyadamantan-2-yl)amino)-1H-pyrrolo[2,3-b]pyridine-5-carboxamide
SMILES Code: O=C(C1=CN=C(NC=C2)C2=C1N[C@H]3[C@]4([H])C[C@@]5([H])C[C@](C4)(O)C[C@]3([H])C5)N

Synonyms

JNJ54781532; JNJ54781532; JNJ 54781532; ASP015K; ASP015K; ASP 015K; Peficitinib;

In Vitro	In vitro activity: ASP015K suppresses the IL-2-induced proliferation of human T cells with greater potency than EPO-induced proliferation of human erythroleukemia cells. In human whole blood, ASP015K inhibits STAT5 phosphorylation (pSTAT5). Kinase Assay: Human JAK1, JAK2, JAK3, TYK2-domains assays performed using streptavidin-coated 96-well plates. Reaction mixture contained 15 mM Tris-HCl (pH 7.5), 0.01% Tween 20, 2 mM dithiothreitol, 10 mM MgCl2, 250 nM Biotin-Lyn-Substrate-2 (for JAK1, 2 and 3) or Biotin-IRS1-Substrate (for TYK2), and ATP (at final concentrations of 200 μM [JAK1], 10 μM [JAK2], 8 μM [JAK3], and 4 μM [TYK2]). Peficitinib or tofacitinib is dissolved in DMSO. The reaction is initiated by adding the kinase domain, followed by incubation at room temperature for 1 h. Kinase activity is measured as the rate of phosphorylation of Biotin-Lyn-Substrate-2 or Biotin-IRS-Substrate using HRP-conjugated anti-phosphotyrosine antibody (HRP-PY-20) using a phosphotyrosine-specific ELISA. TYK2 kinase assay of Peficitinib is performed with the ATP concentration of 10 μM Cell Assay: Erythropoietin regulates haematopoiesis (the production of blood cells). Treatment with ASP015K inhibited the human T-cell proliferation induced by IL-2. And this effect was greater than the effect to inhibit EPO-induced human erythroleukemia cell proliferation. In human whole blood, ASP015K concentration-dependently inhibited STAT5 phosphorylation (pSTAT5).
In Vivo	In the rat AIA model, ASP015K (p.o.) significantly decreases paw swelling and ankle bone destruction score.
Animal model	In healthy volunteers, STAT5-P was dose-dependently inhibited by ASP015K. When the doses of ASP015K were 60, 120, 200, or 300 mg, the mean peak percentage inhibitions of STAT5-P were 84%, 85%, 92%, and 93%, respectively. Plasma ASP015K inhibited STAT5-P with an EC50 value of 48 ng/mL, a shape factor (γ) of ~1.2, and an estimated Emax close to 100%. On days 1, 7, and 14, at ~2 hours after treatment with ASP015K at multiple doses, the peak of median percentage of STAT5-P inhibition appeared.
Formulation & Dosage	For the oral administration regimen, four of the adjuvant-injected groups receive Peficitinib (1, 3, 10, and 30 mg/kg) dissolved in 0.5% methylcellulose (MC) once daily. Rats in the normal and control groups receive 0.5% MC alone.
References	Arthritis Rheumatol. 2016 Oct 16. doi: 10.1002/art.39955; Ann Rheum Dis. 2016 Jun;75(6):1057-64.

In Vitro

In vitro activity: ASP015K suppresses the IL-2-induced proliferation of human T cells with greater potency than EPO-induced proliferation of human erythroleukemia cells. In human whole blood, ASP015K inhibits STAT5 phosphorylation (pSTAT5).

Kinase Assay: Human JAK1, JAK2, JAK3, TYK2-domains assays performed using streptavidin-coated 96-well plates. Reaction mixture contained 15 mM Tris-HCl (pH 7.5), 0.01% Tween 20, 2 mM dithiothreitol, 10 mM MgCl2, 250 nM Biotin-Lyn-Substrate-2 (for JAK1, 2 and 3) or Biotin-IRS1-Substrate (for TYK2), and ATP (at final concentrations of 200 μM [JAK1], 10 μM [JAK2], 8 μM [JAK3], and 4 μM [TYK2]). Peficitinib or tofacitinib is dissolved in DMSO. The reaction is initiated by adding the kinase domain, followed by incubation at room temperature for 1 h. Kinase activity is measured as the rate of phosphorylation of Biotin-Lyn-Substrate-2 or Biotin-IRS-Substrate using HRP-conjugated anti-phosphotyrosine antibody (HRP-PY-20) using a phosphotyrosine-specific ELISA. TYK2 kinase assay of Peficitinib is performed with the ATP concentration of 10 μM

Cell Assay: Erythropoietin regulates haematopoiesis (the production of blood cells). Treatment with ASP015K inhibited the human T-cell proliferation induced by IL-2. And this effect was greater than the effect to inhibit EPO-induced human erythroleukemia cell proliferation. In human whole blood, ASP015K concentration-dependently inhibited STAT5 phosphorylation (pSTAT5).

In Vivo

In the rat AIA model, ASP015K (p.o.) significantly decreases paw swelling and ankle bone destruction score.

Animal model

In healthy volunteers, STAT5-P was dose-dependently inhibited by ASP015K. When the doses of ASP015K were 60, 120, 200, or 300 mg, the mean peak percentage inhibitions of STAT5-P were 84%, 85%, 92%, and 93%, respectively. Plasma ASP015K inhibited STAT5-P with an EC50 value of 48 ng/mL, a shape factor (γ) of ~1.2, and an estimated Emax close to 100%. On days 1, 7, and 14, at ~2 hours after treatment with ASP015K at multiple doses, the peak of median percentage of STAT5-P inhibition appeared.

Formulation & Dosage

For the oral administration regimen, four of the adjuvant-injected groups receive Peficitinib (1, 3, 10, and 30 mg/kg) dissolved in 0.5% methylcellulose (MC) once daily. Rats in the normal and control groups receive 0.5% MC alone.

References

Arthritis Rheumatol. 2016 Oct 16. doi: 10.1002/art.39955; Ann Rheum Dis. 2016 Jun;75(6):1057-64.

CAS NO:	944118-01-8
规格:	≥98%

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