Baricitinib

製品コードS2851 バッチS285103

化学情報

	Synonyms	INCB028050, LY3009104	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₁₆H₁₇N₇O₂S
	分子量	371.42	CAS No.	1187594-09-7
Solubility (25°C)*	体外	DMSO	74 mg/mL (199.23 mM)
		Water	Insoluble
		Ethanol	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	Baricitinib is a selective JAK1 and JAK2 inhibitor with IC50 of 5.9 nM and 5.7 nM in cell-free assays, ~70 and ~10-fold selective versus JAK3 and Tyk2, no inhibition to c-Met and Chk2. Baricitinib is found to reduce or interrupt the passage of the virus into target cells and is used in the treatment research for COVID-19. Phase 3.
in vitro	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 PBMCs. Baricitinib also inhibits pSTAT3 stimulated by IL-23 with IC50 od 20 nM in isolated naive T-cells. ^[1]
in vivo	Baricitinib inhibits IL-6–stimulated phosphorylation of STAT3 in whole blood with an IC50 of 128 nM. Baricitinib (10 mg/kg p.o.) is expected to inhibit JAK1/2 signaling (by ≥50%) in rats for about 8 hours. Baricitinib (10 mg/mL, p.o.) inhibits disease scores in dose-dependent manner in rats with established disease in the adjuvant arthritis model. Baricitinib treatment, compared with vehicle, inhibits the increase in hind paw volumes during the 2 weeks of treatment by 50% at a dose of 1 mg/kg and >95% at doses of 3 mg/kg or 10 mg/kg. Baricitinib treatment, compared with vehicle, also inhibits composite score of immune infiltrate, edema, and periarticular tissue appearance by 27% at a dose of 1 mg/kg, 64% at doses of 3 mg/kg and 82% at doses of 10 mg/kg in rats with established disease in the adjuvant arthritis model. Baricitinib reduces bone resorption by 15%, 61%, and 67% with increasing dose level (1, 3, and 10 mg/kg) in rats with established disease in the adjuvant arthritis model. Baricitinib (10 mg/kg, daily for 2 wk, p.o.) results in radiographic improvements with restoration of the normal architecture and appearance to the ankle and tarsals in rats with established disease in the adjuvant arthritis model. Baricitinib reduces levels of pSTAT3 in a dose- and time-dependent manner in the peripheral blood of rAIA animals. Baricitinib (10 mg/mL, p.o.) improves a composite score of joint damage by 47% in the murine CIA model. Baricitinib (10 mg/kg) reduces pannus (74%) and bone damage (78%) and improves cartilage damage (43%) and signs of inflammation (33%), resulting in a 53% improvement in an aggregate score of disease in the collagen Ab-induced arthritis (CAIA) murine model. Baricitinib (10 mg/kg) inhibits the delayed-type hypersensitivity response by 48% in both the CIA and CAIA models. ^[1] Baricitinib is efficacious in active rheumatoid arthritis patients refractory to disease modifying drugs and biologics. ^[2] Baricitinib preferentially inhibits JAK1 and JAK2, with 10-fold selectivity over Tyk2 and 100-fold over JAK3. The observed effects of GLPG-0634 on the ACR20, albeit in a smaller study, appear to be at least as good as that seen with tofacitinib and superior to that of baricitinib, since baricitinib only moderately affect the ACR20 values in Phase IIa clinical studies. ^[3] Baricitinib has the dose-limiting side-effect of inducing anaemia which has been attributed to its effects on JAK2 but has clearly shown efficacy. ^[4]

製品説明

Baricitinib is a selective JAK1 and JAK2 inhibitor with IC50 of 5.9 nM and 5.7 nM in cell-free assays, ~70 and ~10-fold selective versus JAK3 and Tyk2, no inhibition to c-Met and Chk2. Baricitinib is found to reduce or interrupt the passage of the virus into target cells and is used in the treatment research for COVID-19. Phase 3.

in vitro

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 PBMCs. Baricitinib also inhibits pSTAT3 stimulated by IL-23 with IC50 od 20 nM in isolated naive T-cells. ^[1]

in vivo

Baricitinib inhibits IL-6–stimulated phosphorylation of STAT3 in whole blood with an IC50 of 128 nM. Baricitinib (10 mg/kg p.o.) is expected to inhibit JAK1/2 signaling (by ≥50%) in rats for about 8 hours. Baricitinib (10 mg/mL, p.o.) inhibits disease scores in dose-dependent manner in rats with established disease in the adjuvant arthritis model. Baricitinib treatment, compared with vehicle, inhibits the increase in hind paw volumes during the 2 weeks of treatment by 50% at a dose of 1 mg/kg and >95% at doses of 3 mg/kg or 10 mg/kg. Baricitinib treatment, compared with vehicle, also inhibits composite score of immune infiltrate, edema, and periarticular tissue appearance by 27% at a dose of 1 mg/kg, 64% at doses of 3 mg/kg and 82% at doses of 10 mg/kg in rats with established disease in the adjuvant arthritis model. Baricitinib reduces bone resorption by 15%, 61%, and 67% with increasing dose level (1, 3, and 10 mg/kg) in rats with established disease in the adjuvant arthritis model. Baricitinib (10 mg/kg, daily for 2 wk, p.o.) results in radiographic improvements with restoration of the normal architecture and appearance to the ankle and tarsals in rats with established disease in the adjuvant arthritis model. Baricitinib reduces levels of pSTAT3 in a dose- and time-dependent manner in the peripheral blood of rAIA animals. Baricitinib (10 mg/mL, p.o.) improves a composite score of joint damage by 47% in the murine CIA model. Baricitinib (10 mg/kg) reduces pannus (74%) and bone damage (78%) and improves cartilage damage (43%) and signs of inflammation (33%), resulting in a 53% improvement in an aggregate score of disease in the collagen Ab-induced arthritis (CAIA) murine model. Baricitinib (10 mg/kg) inhibits the delayed-type hypersensitivity response by 48% in both the CIA and CAIA models. ^[1]

Baricitinib is efficacious in active rheumatoid arthritis patients refractory to disease modifying drugs and biologics. ^[2]

Baricitinib preferentially inhibits JAK1 and JAK2, with 10-fold selectivity over Tyk2 and 100-fold over JAK3. The observed effects of GLPG-0634 on the ACR20, albeit in a smaller study, appear to be at least as good as that seen with tofacitinib and superior to that of baricitinib, since baricitinib only moderately affect the ACR20 values in Phase IIa clinical studies. ^[3]

Baricitinib has the dose-limiting side-effect of inducing anaemia which has been attributed to its effects on JAK2 but has clearly shown efficacy. ^[4]

プロトコル(参考用のみ)

キナーゼアッセイ	Biochemical assays
キナーゼアッセイ	Enzyme assays are performed using a homogeneous time-resolved fluorescence assay with recombinant epitope tagged kinase domains (JAK1, 837-1142; JAK2, 828-1132; JAK3, 718-1124; Tyk2, 873-1187) or full-length enzyme (cMET and Chk2) and peptide substrate. Each enzyme reaction is performed with or without test compound (11-point dilution), JAK, cMET, or Chk2 enzyme, 500 nM (100 nM for Chk2) peptide, ATP (at the Km specific for each kinase or 1 mM), and 2.0% DMSO in assay buffer. The calculated IC50 value is the compound concentration required for inhibition of 50% of the fluorescent signal.
細胞アッセイ	細胞株	PBMCs
	濃度	5.9 nM (JAK1) and 5.7 nM (JAK2)
	反応時間
	実験の流れ	Cells were treated with indicated concentrations of drug.
動物実験	動物モデル	Collagen-induced arthritis (CIA) mice
	投薬量	10 mg/mL
	投与方法	orally

参考

[4] Norman P, et al. Expert Opin Ther Pat, 2012, 22(9), 1105-1109.

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カスタマーフィードバック

: , , Nat Cell Biol,2014, 17(1):57-67

: Data from [Data independently produced by , , Br J Haematol, 2017, 177(2):271-282]

: Data from [Data independently produced by , , J Physiol, 2015, 593(24):5269-82]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Macrophage re-programming by JAK inhibitors relies on MAFB [ Cell Mol Life Sci, 2024, 81(1):152]	PubMed: 38528207
A panel of janus kinase inhibitors identified with anti-inflammatory effects protect mice from lethal influenza virus infection [ Antimicrob Agents Chemother, 2024, 68(4):e0135023.]	PubMed: 38470034
Pacritinib inhibits proliferation of primary effusion lymphoma cells and production of viral interleukin-6 induced cytokines [ Sci Rep, 2024, 14(1):4125]	PubMed: 38374336
Interferon signaling promotes tolerance to chromosomal instability during metastatic evolution in renal cancer [ Nat Cancer, 2023, 4(7):984-1000]	PubMed: 37365326
Interferon signaling promotes tolerance to chromosomal instability during metastatic evolution in renal cancer [ Nat Cancer, 2023, 4(7):984-1000]	PubMed: 37365326
Matrix mechanics regulate the polarization state of bone marrow-derived neutrophils through the JAK1/STAT3 signaling pathway [ Acta Biomater, 2023, 168:159-173]	PubMed: 37467837
EndoC-βH5 cells are storable and ready-to-use human pancreatic beta cells with physiological insulin secretion [ Mol Metab, 2023, 76:101772]	PubMed: 37442376
Effect of JAK inhibitors on the three forms of bone damage in autoimmune arthritis: joint erosion, periarticular osteopenia, and systemic bone loss [ Inflamm Regen, 2023, 43(1):44]	PubMed: 37726797
Deucravacitinib, a tyrosine kinase 2 pseudokinase inhibitor, protects human EndoC-βH1 β-cells against proinflammatory insults [ Front Immunol, 2023, 10.3389/fimmu.2023.1263926]	PubMed: 37854597
Impact of Combined Baricitinib and FTI Treatment on Adipogenesis in Hutchinson-Gilford Progeria Syndrome and Other Lipodystrophic Laminopathies [ Cells, 2023, 12(10)1350]	PubMed: 37408186

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人間や獣医の診断であるか治療的な使用のためにでない。

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