JAK/Janus kinases; Ilunocitinib targets JAK1, JAK2, and TYK2 (tyrosine kinase 2); no specific IC50, Ki, or EC50 values are provided in the text.

Protein kinases (PKs) are a group of enzymes that regulate diverse, important biological processes including cell growth, survival and differentiation, organ formation and morphogenesis, neovascularization, tissue repair and regeneration, among others. Protein kinases exert their physiological functions through catalyzing the phosphorylation of proteins (or substrates) and thereby modulating the cellular activities of the substrates in various biological contexts. In addition to the functions in normal tissues/organs, many protein kinases also play more specialized roles in a host of human diseases including cancer. A subset of protein kinases (also referred to as oncogenic protein kinases), when dysregulated, can cause tumor formation and growth, and further contribute to tumor maintenance and progression. Thus far, oncogenic protein kinases represent one of the largest and most attractive groups of protein targets for cancer intervention and drug development. The Janus Kinase (JAK) family plays a role in the cytokine-dependent regulation of proliferation and function of cells involved in immune response. Currently, there are four known mammalian JAK family members: JAKl (also known as Janus kinase- 1), JAK2 (also known as Janus kinase-2), JAK3 (also known as Janus kinase, leukocyte; JAKL; L-JAK and Janus kinase-3) and TYK2 (also known as protein-tyrosine kinase T). The JAK proteins range in size from 120 to 140 kDa and comprise seven conserved JAK homology (JH) domains; one of these is a functional catalytic kinase domain, and another is a pseudokinase domain potentially serving a regulatory function and/or serving as a docking site for STATs. Blocking signal transduction at the level of the JAK kinases holds promise for developing treatments for inflammatory diseases, autoimmune diseases, myeloproliferative diseases, and human cancers, to name a few. Inhibition of the JAK kinases is also envisioned to have therapeutic benefits in patients suffering from skin immune disorders such as psoriasis, and skin sensitization. Accordingly, inhibitors of Janus kinases or related kinases are widely sought and several publications report effective classes of compounds. For example, certain JAK inhibitors, including pyrrolopyridine and pyrrolopyrimidines, are reported in U.S. Ser. No. 11/637,545, filed December 12, 2006.

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Ilunocitinib demonstrates high in vitro potency for inhibiting JAK1, JAK2, and TYK2, as evidenced by unpublished data showing robust inhibition of these kinases in enzymatic assays. This activity suggests strong interference with cytokine signaling pathways critical to inflammation and pruritus in canine atopic dermatitis.[1]

In a randomized, blinded trial involving 338 dogs with canine atopic dermatitis (cAD), Ilunocitinib (0.6–0.8 mg/kg once daily) rapidly reduced pruritus and skin lesions. From Day 0 to Day 14, mean Pruritus Visual Analog Scale (PVAS) scores decreased similarly to oclacitinib, with both groups showing approximately 50% reduction from baseline. From Day 28 to Day 112, mean PVAS scores were significantly lower for Ilunocitinib compared to oclacitinib (p < 0.003), with continuous improvement observed throughout the treatment period. Additionally, a greater proportion of Ilunocitinib-treated dogs achieved clinical remission of pruritus (defined as PVAS < 2), reaching 77% at Day 112 versus 53% for oclacitinib (p < 0.04 at Days 56 and 112). [1]

For skin lesions, assessed using the Canine Atopic Dermatitis Extent and Severity Index (CADESI-04), Ilunocitinib showed rapid improvement: scores dropped to less than half of baseline by Day 14. From Day 28 to Day 112, mean CADESI-04 scores were significantly lower for Ilunocitinib compared to oclacitinib (p < 0.023). By Day 112, 69% of Ilunocitinib-treated dogs achieved clinical remission (CADESI-04 < 10), numerically higher than oclacitinib (64%). The anti-inflammatory effect is attributed to disruption of the itch-scratch cycle and inhibition of pro-inflammatory cytokine signaling via JAK-STAT pathways. [1]

Owner and investigator assessments of overall response to treatment (ORTT and IRTT) significantly favored Ilunocitinib from Day 28 onward (p ≤ 0.002), indicating superior clinical improvement and quality of life. [1]

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Ilunocitinib (LY-3411067) is a novel and potent Janus kinase inhibitor approved for veterinary use.

Dogs were randomized to receive Ilunocitinib tablets orally at 0.6–0.8 mg/kg body weight once daily for up to 112 days. Tablets were administered with or without food, at the owner's discretion, and given at approximately the same time each day. The study was a prospective, double-blinded, randomized, positive-controlled field trial conducted at 25 veterinary clinics across Germany, Hungary, Ireland, and Portugal. Efficacy assessments included owner-reported PVAS and investigator-assessed CADESI-04 at baseline (Day 0), Day 14 (±2 days), Day 28 (±2 days), Day 56 (±3 days), and optionally at Day 84 (±3 days) and Day 112 (±3 days) for dogs in the continuation phase. Safety monitoring included physical examinations, hematology, and serum chemistry at all visits. [1]

Ilunocitinib exhibited a favorable safety profile over 112 days, with adverse events (AEs) similar to oclacitinib. Digestive tract disorders were most common, including emesis (13.6% incidence) and diarrhea. Systemic disorders occurred in 5.3% of dogs, and skin/appendage disorders in 5.9%. Most AEs were mild and assessed as possibly treatment-related. Hematological changes included decreases in leucocyte counts, primarily neutrophils and eosinophils, but values remained within normal laboratory reference ranges. No clinically relevant abnormalities were observed in serum biochemistry. Serious adverse events (e.g., seminoma) were not treatment-related. [1]

[1]. Comparative efficacy and safety of ilunocitinib and oclacitinib for the control of pruritus and associated skin lesions in dogs with atopic dermatitis. Vet Dermatol. 2025 Apr;36(2):165-176.

[2]. Azetidine and cyclobutane derivatives as jak inhibitors. Patent. WO2009114512A1.

Ilunocitinib is a novel Janus kinase inhibitor (JAKi) designed for once-daily oral administration to control pruritus and skin lesions in dogs with atopic dermatitis. Its mechanism involves potent inhibition of JAK1, JAK2, and TYK2, reducing signaling of pro-inflammatory cytokines (e.g., IL-31) via the JAK-STAT pathway, which is central to cAD pathogenesis. Clinical relevance includes superior long-term efficacy over oclacitinib, with higher rates of clinical remission and reduced caregiver burden due to consistent dosing. No FDA alerts or specific drug interactions were reported, and it is indicated for managing cAD manifestations. [1]

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Background: Janus kinase inhibitors (JAKi) have been shown to reduce pruritus and improve associated inflammatory skin lesions in canine atopic dermatitis (cAD). Objective: To evaluate the efficacy and safety of ilunocitinib, in comparison to oclacitinib, for the control of cAD in a randomised, blinded trial. Animals: Three-hundred-and-thirty-eight dogs with cAD. Materials and methods: Dogs were randomised to receive oclacitinib (0.4-0.6 mg/kg twice daily for 14 days; then once daily) or ilunocitinib (0.6-0.8 mg/kg once daily), for up to 112 days. Owners assessed pruritus using an enhanced Visual Analog Scale (PVAS). Investigators assessed skin lesions using the Canine Atopic Dermatitis Extent and Severity Index, 4th interaction (CADESI-04). Results: Reduction in pruritus and CADESI-04 scores was similar for both treatment groups from Day (D)0-D14. PVAS scores increased between D14 and D28 for oclacitinib and decreased for ilunocitinib. On D28 to D112, mean PVAS and CADESI-04 scores were significantly lower for ilunocitinib compared to oclacitinib (p ≤ 0.003 and p ≤ 0.023, respectively). On D28 to D112, a greater number of ilunocitinib-treated dogs achieved clinical remission of pruritus (i.e. PVAS score <2). Subjective assessment of overall response was significantly better for ilunocitinib on D28 to D112 (p ≤ 0.002). Both drugs demonstrated similar safety throughout the study. Conclusions and clinical relevance: Ilunocitinib rapidly and safely controlled signs of cAD. Ilunocitinib demonstrated significantly better control of pruritus and skin lesions compared to oclacitinib, with more dogs achieving clinical remission of pruritus. [1]

C17H17N7O2S

383.4276

383.116

C, 53.25; H, 4.47; N, 25.57; O, 8.35; S, 8.36

1187594-14-4

44231134

White to off-white solid powder

-0.3

1

7

5

27

734

0

S(C1([H])C([H])([H])C1([H])[H])(N1C([H])([H])C(C([H])([H])C#N)(C1([H])[H])N1C([H])=C(C2=C3C([H])=C([H])N([H])C3=NC([H])=N2)C([H])=N1)(=O)=O

RVOUEXFKIYNODQ-UHFFFAOYSA-N

InChI=1S/C17H17N7O2S/c18-5-4-17(9-23(10-17)27(25,26)13-1-2-13)24-8-12(7-22-24)15-14-3-6-19-16(14)21-11-20-15/h3,6-8,11,13H,1-2,4,9-10H2,(H,19,20,21)

2-[1-cyclopropylsulfonyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrazol-1-yl]azetidin-3-yl]acetonitrile

Ilunocitinib; 1187594-14-4; Ilunocitinib [USAN]; LY3411,067; N3TB5AH8B9; LY3411,067; LY3411067; 2-[1-cyclopropylsulfonyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrazol-1-yl]azetidin-3-yl]acetonitrile; ILUNOCITINIB [INN]; N3TB5AH8B9; UNII-N3TB5AH8B9; LY-3411067; WHO 11894;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~250 mg/mL (~652.01 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (5.42 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (5.42 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (5.42 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)