| Size | Price | Stock | Qty |
|---|---|---|---|
| 100mg |
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| 500mg |
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| Targets |
JAK/Janus kinase； JAK1 （IC50 = 6.6 nmol L–1); JAK2 (IC50 = 3.5 nmol L–1)
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|---|---|
| ln Vitro |
Pumecitinib is a newly developed JAK1/2i. The IC50 for JAK1 and JAK2 are 6.6 nmol L–1 and 3.5 nmol L–1, respectively.
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| ln Vivo |
At Week 8, the percentage changes from baseline in EASI score were -83.6%, -44.0%, and -22.0% for the pumecitinib 3% gel twice-daily, pumecitinib 3% gel once-daily, and placebo groups, respectively. Both pumecitinib treatment regimens demonstrated significantly greater efficacy compared to placebo (P < 0.006), with the twice-daily pumecitinib 3% gel regimen showing a superior effect over the once-daily regimen (P < 0.001). Improvements in other efficacy endpoints were also observed in participants receiving pumecitinib versus those on placebo, and the pumecitinib 3% gel twice-daily regimen consistently exhibited better efficacy than the once-daily treatment. Regarding safety, the incidence of adverse events was 48% in both the pumecitinib and placebo groups. The safety profiles were generally comparable between the pumecitinib and placebo groups, and the treatment was well tolerated. Mean plasma drug concentrations remained low (range 38-104 pg mL⁻¹) throughout the 8-week treatment period.
Conclusions: Pumecitinib 3% gel demonstrated favorable efficacy and safety profiles in the treatment of adults with mild-to-moderate atopic dermatitis (AD). Notably, the pumecitinib 3% gel twice-daily regimen proved more effective than the once-daily regimen for treating mild-to-moderate AD. It was well tolerated and resulted in low systemic drug exposure when applied topically. These findings suggest that pumecitinib 3% gel could represent a new topical JAK inhibitor option for managing mild-to-moderate AD.
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| Animal Protocol |
This Phase 2 study enrolled 139 adults with mild-to-moderate atopic dermatitis (AD). Participants were randomized 1:1:1 to receive either pumecitinib 3% gel twice daily (n=47), pumecitinib 3% gel once daily (n=46), or a placebo gel (n=46) for eight weeks.
The primary efficacy endpoint was the percentage change from baseline in the Eczema Area and Severity Index (EASI) score at Week 8. Secondary endpoints included the proportion of participants achieving an Investigator's Global Assessment (IGA) score of 0 or 1 (with a ≥2-point improvement from baseline), as well as EASI-50, EASI-75, and EASI-90 responses at Week 8. Changes in quality of life were also assessed. Throughout the study, safety, local tolerability, and pharmacokinetic parameters were monitored.
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| ADME/Pharmacokinetics |
Of 87 participants who had pharmacokinetics measured, plasma pumecitinib was detected in 32 of 41 (78%) people in the pumecitinib 3% once-daily group and 38 of 46 (83%) in the pumecitinib 3% twice-daily group (defined as pumecitinib detected in a minimum of one plasma sample from a participant). The mean (SD) drug concentrations at weeks 1, 2, 4 and 8 were 42.98 (94.62) pg mL–1, 72.84 (247.09) pg mL–1, 38.30 (66.55) pg mL–1 and 53.27 (95.55) pg mL–1, respectively, in the pumecitinib 3% once-daily group and 103.58 (243.78) pg mL–1, 89.75 (135.90) pg mL–1, 75.53 (110.18) pg mL–1 and 97.87 (156.99) pg mL–1, respectively, in the pumecitinib 3% twice-daily group. The average pumecitinib concentration in participants in the pumecitinib 3% twice-daily group was approximately twice the concentration found in those in the pumecitinib 3% once-daily group. No trend of drug accumulation in the body was observed. [1]
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| Toxicity/Toxicokinetics |
Forty-eight per cent (n = 45/93) of participants in the combined pumecitinib groups experienced AEs [n = 26/46 (57%) in the pumecitinib 3% once-daily group; n = 19/47 (40%) in the pumecitinib 3% twice-daily group]; 89% of the AEs were mild and 11% were moderate in severity (Table 3). Forty-eight per cent (n = 22/46) of those in the placebo group experienced AEs, of which one case (2%) was severe (worsening AD); the rest were mild-to-moderate in severity. The most commonly reported AEs in the combined pumecitinib groups were high uric acid (4% vs. 0%, pumecitinib vs. placebo) and high bilirubin (4% vs. 0%, pumecitinib vs. placebo). One participant (2%) in the placebo group discontinued treatment due to an AE of worsening AD. AESIs of folliculitis (n = 1/93; 1%) and skin infection (n = 1/93; 1%) were reported in the combined pumecitinib groups, while folliculitis (n = 1, 2%), application site pain (n = 1, 2%) and worsening of AD (n = 1, 2%) were reported in the placebo group. Three SAEs were reported in the placebo group during the study; these were deemed by the principal investigator and study sponsor as being unrelated to pumecitinib treatment (type 2 diabetes, n = 1; appendicitis, n = 1; fibroadenoma and mammary hyperplasia, n = 1). No severe infections or deaths occurred in the study. [1]
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| References | |
| Additional Infomation |
Background: We conducted a phase IIb clinical trial of pumecitinib 3% gel (PG-011), a novel selective Janus kinase (JAK)1/2 inhibitor, applied topically to treat mild-to-moderate atopic dermatitis (AD).
Objectives: To assess pumecitinib 3% gel for its efficacy and safety in treating adult patients with mild-to-moderate AD, and to determine the optimal treatment regimen. [1]
In this study, plasma concentrations of pumecitinib remained low (<1 ng mL⁻¹) throughout the treatment period. As expected, the mean concentration in the twice-daily application group was approximately twice that of the once-daily group. Importantly, this elevated concentration did not result in additional safety concerns. Treatment-emergent adverse events (TEAEs) were mostly mild in severity, and all patients recovered during the study. No significant adverse events were reported at the application site, indicating that the gel formulation was well tolerated. Pumecitinib 3% gel demonstrated clinical efficacy in treating AD, with an onset of action as early as week 1. The twice-daily regimen proved more effective than the once-daily regimen. However, the study did not find significant differences between pumecitinib 3% and placebo in terms of itch relief or improvements in POEM and DLQI scores after eight weeks of treatment. This was an eight-week study conducted exclusively in adult participants of Chinese Han ethnicity within a single country. To further validate these findings, longer-term studies with larger sample sizes and more diverse ethnic populations are warranted. Such research would help confirm the efficacy, long-term safety, and impact on quality of life associated with pumecitinib 3% gel. In conclusion, pumecitinib 3% gel appears to be a promising new topical treatment option for patients with AD, offering good efficacy, a favorable safety profile, and low systemic exposure.[1] |
| Molecular Formula |
C17H20N8O2S
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|---|---|
| Molecular Weight |
400.458100318909
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| Exact Mass |
400.142
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| Elemental Analysis |
C, 50.99; H, 5.03; N, 27.98; O, 7.99; S, 8.01
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| CAS # |
2401057-12-1
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| PubChem CID |
141761076
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| Appearance |
White to off-white solid powder
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| LogP |
-0.4
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
28
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| Complexity |
738
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N1(S(C(C)C)(=O)=O)CC(N2C=C(C3N=CN=C4NC=CC4=3)C(N)=N2)(CC#N)C1
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| InChi Key |
OUXYFMCMGWQWQF-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H20N8O2S/c1-11(2)28(26,27)24-8-17(9-24,4-5-18)25-7-13(15(19)23-25)14-12-3-6-20-16(12)22-10-21-14/h3,6-7,10-11H,4,8-9H2,1-2H3,(H2,19,23)(H,20,21,22)
|
| Chemical Name |
2-[3-[3-amino-4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrazol-1-yl]-1-propan-2-ylsulfonylazetidin-3-yl]acetonitrile
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~125 mg/mL (~312.14 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.19 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4971 mL | 12.4856 mL | 24.9713 mL | |
| 5 mM | 0.4994 mL | 2.4971 mL | 4.9943 mL | |
| 10 mM | 0.2497 mL | 1.2486 mL | 2.4971 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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