Tofacitinib (CP-690550) is a potent, small molecule inhibitor of JAK-3, which exhibiting potent effects in preclinical transplantation and arthritis models. It displays greater antiproliferative and pro-apoptotic activity against murine multipotent factor-dependent cell Patersen-erythropoietin receptor (FDCP-EpoR) cells harboring JAK2(V617F) compared with JAK2(WT). JAK-3 has been shown to play a key role in cytokine signaling via gammac, e.g. IL-2, 4, 7, 9, 15, 21. In vitro, Tofacitinib effectively inhibited a murine mixed lymphocyte reaction (MLR) (IC50= 91 nm). Mice chronically dosed with CP-690550 (1.5-15 mg/kg/day) demonstrated dose- and time-dependent alterations in lymphocyte subsets when examined by flow cytometry. The most dramatic change observed was a 96% reduction in splenic NK1.1 + TCRbeta- cell numbers following 21 days of treatment. Delayed-type hypersensitivity (DTH) responses in sensitized mice were reduced in a dose-dependent manner following treatment with the JAK-3 inhibitor (1.87-30 mg/kg, s.c.). Extended survival of neonatal Balb/c hearts implanted into the ear pinna of MHC mismatched C3H/HEN mice was observed with CP-690550 monotherapy (10-30 mg/kg/day), but improved upon combination with cyclosporin (10 mg/kg/day). Furthermore, the ability of Tofacitinib to extend cardiac allograft survival in murine models suggests it may afford a new treatment for prevention of transplant rejection.
EMBO Mol Med. 2022 Aug 8;14(8):e15653.
Single‐cell transcriptomics reveals a senescence‐associated IL‐6/CCR6 axis driving radiodermatitis
Tofacitinib purchased from AbMole
Front Immunol. 2022 May 23;13:866638.
A Novel STAT3 Gain-of-Function Mutation in Fatal Infancy-Onset Interstitial Lung Disease
Tofacitinib purchased from AbMole
Front Immunol. 2021 Jul 29;12:675542.
Tofacitinib Ameliorates Lupus Through Suppression of T Cell Activation Mediated by TGF-Beta Type I Receptor
Tofacitinib purchased from AbMole
J Virol. 2020 Feb 14;94(5):e01791-19.
Targeting Kaposi's Sarcoma-Associated Herpesvirus ORF21 Tyrosine Kinase and Viral Lytic Reactivation by Tyrosine Kinase Inhibitors Approved for Clinical Use
Tofacitinib purchased from AbMole
Cell Stem Cell. 2019 Apr 4;24(4):654-669.e6.
A Subset of TREM2+ Dermal Macrophages Secretes Oncostatin M to Maintain Hair Follicle Stem Cell Quiescence and Inhibit Hair Growth.
Tofacitinib purchased from AbMole
Arch Dermatol Res. 2018 Oct 5.
Effect of tofacitinib on the expression of noggin/BMP-4 and hair growth stimulation in mice
Tofacitinib purchased from AbMole
TJPS. 2017;41 (Supplement Issue): 225-228.
Topical tofacitinib reduce expression of BMP-4 in mouse hair follicle
Tofacitinib purchased from AbMole
Arch Dermatol Res. 2017 Sep 7.
Efficacy of topical tofacitinib in promoting hair growt in non‑scarring alopecia: possible mechanism via VEGF induction
Tofacitinib purchased from AbMole
Sci Adv. 2015 Oct 23.
Pharmacologic inhibition of JAK-STAT signaling promotes hair growth.
Tofacitinib purchased from AbMole
Nat Med. 2014 Sep;20(9):1043-9.
Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition.
Tofacitinib purchased from AbMole
Cell Experiment | |
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Cell lines | cytokine-dependent NK92 cell line |
Preparation method | (A) After cytokine starvation for 24 hours, NK92 cells were stimulated by the addition of human IL-2 for 48 hours with and without the addition of serially increasing concentrations of tofacitinib. 3H-thymidine was added during the last 6 hours of the cultures. Cells were then harvested and analyzed for 3H-thymidine incorporation. (B) Cytokine-starved NK92 cells were stimulated with human IL-2, combined IL-6/IL- 6R, or IL-12 for 48 hours with and without serially increasing concentrations of tofacitinib. (C) The NK92 cells were treated as those in panel B with and without a single 50nM dose of tofacitinib. Data are presented as means ±SD (A-C) and are representative of 3 independent experiments. (D) After cytokine starvation for 24 hours, NK92 cells were stimulated with 30 ng/mL of IL-2, 100 ng/mL of combined IL-6/IL-6R, or 100 ng/mL of IL-12 for 1 hour with and without the addition of tofacitinib. The cell lysates were immunoblotted with an anti–phospho-STAT5 monoclonal antibody and an anti-STAT5 antibody. ß-Actin was used as an input control. Data are representative of 3 independent experiments. |
Concentrations | 0~400 nM |
Incubation time | 48 h |
Animal Experiment | |
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Animal models | IL-15–transgenic CD8 T-cell leukemia–bearing mice |
Formulation | dissolved in polyethylene glycol 300 (PEG300; VWR Scientific Products) |
Dosages | 50 mg/mL |
Administration | continuously administered via a subcutaneous mini-osmotic pump (ALZET) |
Molecular Weight | 312.37 |
Formula | C16H20N6O |
CAS Number | 477600-75-2 |
Solubility (25°C) | DMSO ≥60 mg/mL |
Storage | -20°C, sealed |
Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
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