| Identification | Back Directory | [Name]
Baricitinib phosphate salt | [CAS]
1187595-84-1 | [Synonyms]
INCB-28050
LY-3009104 phosphate
INCB028050 phosphate)
INCB-28050; LY3009104
Baricitinib (phosphate)
Baricitinib phosphate salt
INCB424-Analogue (INCB-28050)
Baricitinib phosphate (LY3009104 phosphate
BARICITINIB PHOSPHATE (LY3009104 PHOSPHATE; INCB028050 PHOSPHATE)
INCB-028050;LY-3009104;INCB 028050;LY 3009104;INCB028050;LY3009104
[1-(Ethylsulfonyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl]acetonitrile phosphate
2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(ethylsulfonyl)azetidin-3-yl)acetonitrile phosphate | [Molecular Formula]
C16H20N7O6PS | [MDL Number]
MFCD25976707 | [MOL File]
1187595-84-1.mol | [Molecular Weight]
469.412 |
| Chemical Properties | Back Directory | [storage temp. ]
Store at -20°C | [solubility ]
insoluble in EtOH; insoluble in H2O; ≥172.6 mg/mL in DMSO | [form ]
White powder. | [color ]
White to yellow | [InChIKey]
FBPOWTFFUBBKBB-UHFFFAOYSA-N | [SMILES]
C(#N)CC1(N2C=C(C3=NC=NC4NC=CC=43)C=N2)CN(S(CC)(=O)=O)C1.P(O)(O)(O)=O |
| Questions And Answer | Back Directory | [IC50 & Target]
JAK2: 5.7 nM (IC50) JAK1: 5.9 nM (IC50) Tyk2: 53 nM (IC50) JAK3: 560 nM (IC50) | [In Vivo]
Baricitinib phosphate treatment, compares with vehicle, inhibits the increase in hind paw volumes during the 2 wk of treatment by 50% at a dose of 1 mg/kg and >95% at doses of 3 or 10 mg/kg. Because baseline paw volume measurements are taken on treatment day 0-in animals with significant signs of disease-it is possible to have >100% inhibition in animals showing marked improvement in swelling[1]. Baricitinib (0.7 mg/day) treated mice exhibits substantially reduced inflammation as assessed by H&E staining, reduced CD8 infiltration, and reduced MHC class I and class II expression when compared with vehicle-control treated mice. CD8+NKG2D+ cells, critical effectors of disease in murine and human alopecia areata (AA), are greatly diminished in Baricitinib treated mice compare with vehicle control treated mice. |
| Hazard Information | Back Directory | [Uses]
Baricitinib is a JAK1 and JAK2 inhibitor and have been used as a promising treatment for rheumatoid arthritis. | [Biological Activity]
direct and indirect inhibition of the jaks has demonstrated rapid and sustained improvement in clinical measures of disease. baricitinib phosphate (incb 028050) is a selective jak1 and jak2 inhibitor. | [Synthesis]
General procedure for the synthesis of [1-(ethylsulfonyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl]acetonitrile phosphates from baricitinib: Barectinib (0.30 g, 0.8 mmol) was dissolved in boiling acetonitrile (7 ml), followed by the titrative addition, over a 30-minute period, of phosphoric acid ( 0.20 g, 2.1 equivalents, 85% aqueous solution) solution in methanol (1.2 ml). The reaction mixture was stirred at 68 °C for 1 h, then slowly cooled to room temperature and continued stirring overnight. The precipitate was collected by filtration and dried at 35 °C for 18 h at 200 mbar to give baricitinib phosphate of form C as a white powder (376 mg, 99.2% yield). The stoichiometric ratio was 1:1.14. | [in vitro]
In cell-based assays, Baricitinib phosphate proves to be a potent inhibitor of JAK signaling and function. In PBMCs, Baricitinib inhibits IL-6-stimulated phosphorylation of the canonical substrate STAT3 (pSTAT3) and subsequent production of the chemokine MCP-1 with IC50 values of 44 nM and 40 nM, respectively. In isolated naive T-cells, INCB028050 also inhibits pSTAT3 stimulated by IL-23 (IC50=20 nM). Importantly, this inhibition prevented the production of two pathogenic cytokines (IL-17 and IL-22) produced by Th17 cells-a subtype of helper T cells with demonstrable inflammatory and pathogenic properties-with an IC50 value of 50 nM. In stark contrast, the structurally similar but ineffective JAK1/2 inhibitors INCB027753 and INCB029843 has no significant effect in any of these assays systems when tested at concentrations up to 10 μM. | [IC 50]
JAK2: 5.7 nM (IC50); JAK1: 5.9 nM (IC50); Tyk2: 53 nM (IC50); JAK3: 560 nM (IC50) | [References]
[1] fridman js, scherle pa, collins r, burn tc, li y, li j, covington mb, thomas b, collier p, favata mf, wen x, shi j, mcgee r, haley pj, shepard s, rodgers jd, yeleswaram s, hollis g, newton rc, metcalf b, friedman sm, vaddi k. selective inhibition of jak1 and jak2 is efficacious in rodent models of arthritis: preclinical characterization of incb028050. j immunol. 2010;184(9):5298-307. |
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| Company Name: |
LETOPHARM LIMITED
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| Telephone: |
+86-21-5821 5861 |
| Website: |
www.letopharm.com |
| Company Name: |
SPIRO PHARMA
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| Telephone: |
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| Website: |
www.spiropharma.com.cn |
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