SHR0302

SKU: orb1218804

Description

SHR0302 is a JAK inhibitor that binds JAK1 with stronger affinity than others (Selectivity for JAK1 is more than 10 times for JAK2, 77 times for JAK3, 420 times for Tyk2).

Key Properties

• CAS Number: 1445987-21-2
• MW: 414.48
• Purity: >98% (HPLC)
• Formula: C₁₈H₂₂N₈O₂S
• SMILES: CN(C(C1)C[C@@H](C2)[C@H]1CN2C(Nc1nc(OC)ns1)=O)c1ncnc2c1cc[nH]2
• Target: JAK
• Solubility: DMSO:30mg/ml(72.38mM; Need ultrasonic)

Bioactivity

• In Vivo:
  Ivarmacitinib (SHR0302; 0.3-3.0 mg/kg; intragastric administration; twice a day; for 14 days; male Sprague-Dawley (SD) rats) treatment suppresses the severity of AA rats by attenuating the arthritis index, arthritis global assessment and paw swelling degree, and alleviated histopathology of spleen and joint of AA rats. Ivarmacitinib can inhibit the proliferation of T, B and fibroblast-like synoviocytes (FLS), and down-regulates cytokines TNF-α, IL-1β, IL-17 and antibody IgG1, IgG2a levels, and suppresses the proportion of Th17 and total B, and inhibits JAK1-STAT3 phosphorylation. Animal model: Male Sprague-Dawley (SD) rats (150-180 g) injected with complete Freund’s adjuvant (CFA). Dosage: 0.3 mg/kg, 1.0 mg/kg, 3.0 mg/kg. Administration: Intragastric administration; twice a day; for 14 days. Result: Suppressed the severity of adjuvant-induced arthritis (AA) rats by attenuating the arthritis index, arthritis global assessment and paw swelling degree, and alleviated histopathology of spleen and joint of AA rats.
• In Vitro:
  Ivarmacitinib (SHR0302; 1 nM-10 μM; 48 hours; HSCs) treatment displays an inhibitory effect on the proliferation of HSCs in a concentration-dependent manner. Ivarmacitinib (1 nM-10 μM) exerts an inhibitory effect on the activation, proliferation and migration of HSCs. Ivarmacitinib (1 nM-10 μM; 48 hours; HSCs) treatment induces the apoptosis of HSCs. Ivarmacitinib (1 nM-10 μM; 48 hours; HSCs) treatment significantly increases the activation of caspase-3 and Bax in HSCs, and decreases the expression of Bcl-2. SHR0302 also inhibits the activation of Akt signaling pathway. Cell Proliferation Assay Cell line: Hepatic stellate cells (HSCs). Concentration: 1 nM, 10 nM, 100 nM, 1 μM, 10 μM. Incubation time: 48 hours. Result: Displayed an inhibitory effect on the proliferation of HSCs, and that inhibition ocurred in a concentration-dependent manner. Apoptosis Analysis Cell line: Hepatic stellate cells (HSCs). Concentration: 1 nM, 10 nM, 100 nM, 1 μM, 10 μM. Incubation time: 48 hours. Result: Induced the apoptosis of HSCs. Western blot analysis. Cell line: Hepatic stellate cells (HSCs). Concentration: 1 nM, 10 nM, 100 nM, 1 μM, 10 μM. Incubation time: 48 hours. Result: Significantly increased the activation of caspase-3 and Bax in HSCs, and decreased the expression of Bcl-2. Also inhibited the activation of Akt signaling pathway.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

ARQ252

Quick Database Links

Gene Symbol

JAK