 Chemical Structure.png)
Deuruxolitinib (CTP-543) is the hexa-deuterated form of Ruxolitinib, which is a marketed JAK1/JAK2 inhibitor. Deuruxolitinib is being studied in clhical trials for treating Alopecia Areata (a form of hair loss).
Leqselvi (deuruxolitinib) is an oral Janus kinase (JAK) inhibitor approved by the U.S. Food and Drug Administration (FDA) for adults with severe alopecia areata (AA). The FDA approved Leqselvi for alopecia areata in July 2024, and it became commercially available in July 2025.Physicochemical Properties
| Molecular Formula | C17H18N6 |
| Molecular Weight | 314.414315700531 |
| Exact Mass | 314.209 |
| Elemental Analysis | C, 64.94; H, 8.33; N, 26.73 |
| CAS # | 1513883-39-0 |
| Related CAS # | Ruxolitinib;941678-49-5;(Rac)-Ruxolitinib-d9;2469553-67-9; 1513883-39-0; 2147706-60-1 (phosphate) |
| PubChem CID | 72704611 |
| Appearance | Typically exists as white to off-white solids at room temperature |
| LogP | 2.1 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 23 |
| Complexity | 453 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | [2H]C1(C(C(C(C1([2H])[2H])([2H])[2H])([2H])[2H])[C@@H](CC#N)N2C=C(C=N2)C3=C4C=CNC4=NC=N3)[2H] |
| InChi Key | HFNKQEVNSGCOJV-FBXGHSCESA-N |
| InChi Code | InChI=1S/C17H18N6/c18-7-5-15(12-3-1-2-4-12)23-10-13(9-22-23)16-14-6-8-19-17(14)21-11-20-16/h6,8-12,15H,1-5H2,(H,19,20,21)/t15-/m1/s1/i1D2,2D2,3D2,4D2 |
| Chemical Name | (3R)-3-(2,2,3,3,4,4,5,5-octadeuteriocyclopentyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrazol-1-yl]propanenitrile |
| Synonyms | Deuruxolitinib; D8-ruxolitinib; CTP-543; Deuruxolitinib [USAN]; 1513883-39-0; 0CA0VSF91Y; UNII-0CA0VSF91Y; |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| Targets | JAK1/2 |
| ln Vitro |
In an in vitro kinase activity assay, deuruxolitinib had greater inhibitory potency for JAK1, JAK2 and TYK2 relative to JAK3. The relevance of inhibition of JAK enzymes to therapeutic effectiveness is not currently known. Deuruxolitinib inhibited whole blood IL-6 stimulated pSTAT3 in healthy subjects 2 hours postdose. The relevance of this finding in patients is unknown.
The Janus kinase‒signal transducer and activator of transcription (JAK-STAT) pathway, which involves four JAK kinases - JAK1, JAK2, JAK3, and tyrosine kinase 2 (Tyk2) - is activated by various cytokine receptors and regulate the expression of mediators responsible for hematopoiesis and immune function, such as type I and type II cytokines and growth factors. JAK signalling involves the recruitment of STATs (signal transducers and activators of transcription) to cytokine receptors, activation and subsequent localization of STATs to the nucleus, leading to modulation of gene expression. Dysregulated JAK activity, leading to aberrant immune responses, has been characterized in various inflammatory conditions, including alopecia areata. For example, high levels of IFN-γ and CD8+NKG2D+T cells, which are activated by JAK signalling, are believed to cause autoantigen expression and an autoimmune attack on hair follicles. Deuruxolitinib is a Janus kinase (JAK) inhibitor that aims to attenuate the inflammatory response around hair follicles. It selectively targets JAK1 and JAK2. Drug compounds have included stable heavy isotopes of elements like carbon and hydrogen, mostly as tracers that affect quantification during drug development. It's possible that the pharmacokinetics and effects of medications cause mutagenesis to be a worry. [2]. Possible benefits of compounds with delayed generation: (1) The pharmacokinetic properties of the molecule, or the possible benefits of delayed generation compounds, may be prolonged by these substances. This may enhance the compound's tolerance, efficacy, and safety. (2) Boost intestinal absorption. Deuterated chemicals have the potential to decrease the level of first-pass renal function that is required in the intestinal wall and colon, hence increasing the amount of non-renal function medications that are able to reach their intended site of action. The ability to be bioavailable incredibly strong, active at low concentrations, and more tolerable. (3) Enhance the properties of metabolism. The production process may lessen toxicity or reactivity, leading to better medications. (4) Boost the security of medications. Deuterated substances Alternatively, they are harmless and can lessen or eliminate the negative effects of medication components. (5) Preserve medicinal qualities. According to earlier research, deuterated molecules should maintain biological efficacy and selectivity comparable to hydrogen analogs. |
| ln Vivo |
Deuruxolitinib is an orally available small molecule inhibitor of Janus kinases that is used to treat severe alopecia areata. Deuruxolitinib is associated with a low rate of transient and usually mild elevations in serum aminotransferase levels during therapy but has not been linked to cases of clinically apparent acute liver injury.
DEURUXOLITINIB is a small molecule drug with a maximum clinical trial phase of III (across all indications) and has 3 investigational indications. Background: Alopecia areata (AA) is a hair loss disorder that can seriously impact quality of life. Janus kinase (JAK) inhibitors, including deuruxolitinib, have previously demonstrated significant hair regrowth in AA. Objective: The Phase 3 THRIVE-AA1 randomized, double-blinded, placebo-controlled trial (NCT04518995) evaluated the safety and efficacy of the oral JAK1/JAK2 inhibitor deuruxolitinib in adult patients with AA. Methods: Patients aged 18-65 years with ≥50% hair loss were randomized to deuruxolitinib 8 mg twice daily, deuruxolitinib 12 mg twice daily, or placebo for 24 weeks. The primary end point was the percentage of patients achieving a Severity of Alopecia Tool score ≤20. A key secondary end point was the percentage of satisfaction of hair patient-reported outcome responders. Results: Significantly higher proportions of patients taking deuruxolitinib met the primary end point (8 mg 29.6%; 12 mg 41.5% versus placebo 0.8%). Both deuruxolitinib doses achieved significant improvements in all secondary end points versus placebo, including satisfaction of hair patient-reported outcome (8 mg 42.1%; 12 mg 53.0% versus placebo 4.7%). Most treatment-emergent adverse events were mild or moderate, consistent with other oral JAK inhibitors. Limitations: Further studies are required to understand longer-term safety, efficacy, and impact of treatment cessation. Conclusion: Both doses of deuruxolitinib were effective for hair regrowth. Patient satisfaction aligned with hair growth.[3] |
| Animal Protocol |
Study procedures [3] Patients were randomized in a 3:5:2 ratio to receive oral deuruxolitinib 12 mg twice daily, deuruxolitinib 8 mg twice daily, or placebo. Randomization was stratified by baseline scalp hair loss (partial [SALT 50-94] or complete/near-complete [SALT ≥95]) and performed using an interactive web-response system. Identical tablets and packaging were used for deuruxolitinib and placebo to maintain investigator and patient/caregiver blinding throughout the study. Individualized dose adjustment was not permitted during the treatment period. |
| ADME/Pharmacokinetics |
Absorption Following oral administration of deuruxolitinib, Cmax and AUCs increased dose-proportionally over a dose range from 8 mg to 48 mg (6 times the approved recommended dosage) in healthy subjects. Steady-state plasma concentrations were achieved within one to two days, with minimal accumulation, after twice daily administration. Deuruxolitinib bioavailability is 90%, with peak plasma concentrations reached within 1.5 hours. No clinically significant differences in the pharmacokinetics of deuruxolitinib were observed following the administration of a high-fat, high-calorie meal (approximately 50% fat and 800-1000 calories). Route of Elimination After a single dose of radiolabeled deuruxolitinib, there was no unchanged dose recovered in either urine or feces. Volume of Distribution The steady-state volume of distribution is approximately 50 L. Protein Binding Deuruxolitinib plasma protein binding is 91.5% and blood to plasma concentration ratio is approximately 1.3. Metabolism / Metabolites Deuruxolitinib is primarily metabolized by CYP2C9 (76%) and CYP3A4 (21%) and to a lesser extent by CYP1A2 (3%). The two most abundant human metabolites C-21714 and C-21717, each of which accounted for approximately 5% of total drug-related AUC and both are approximately 10-fold less pharmacologically active than deuruxolitinib. The exact metabolic pathways of deuruxolitinib and the structures of its metabolites have not been fully characterized. Biological Half-Life The mean elimination half-life is approximately four hours. |
| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation No information is available on the clinical use of deuruxolitinib during breastfeeding. Because deuruxolitinib is 91.5% bound to plasma proteins, the amount in milk is likely to be low. The manufacturer recommends that breastfeeding be discontinued during deuruxolitinib therapy and for 1 week after the last dose. ◉ Effects in Breastfed Infants Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date. Hepatotoxicity In the prelicensure clinical trials in alopecia areata, serum aminotransferase elevations occurred in less than 1% of deuruxolitinib-treated subjects and there were no instances of ALT or AST elevations accompanied by symptoms or jaundice. The elevations were typically mild and transient and did not lead to dose adjustments or discontinuations. In prelicensure studies in alopecia areata, there were no instances of liver related severe adverse events or drug induced liver injury. Since approval of deuruxolitinib, there have been no published reports of hepatotoxicity associated with its use, but clinical experience with it has been limited. Finally, deuruxolitinib is an immune modulatory agent and has the potential of causing reactivation of viral infections including hepatitis B. Other JAK inhibitors have been implicated in rare instances of reactivation of hepatitis B, although the episodes were usually asymptomatic and self-limited in course. The risk of reactivation of hepatitis B in patients with HBsAg or with anti-HBc without HBsAg who are treated with deuruxolitinib has not been defined as patients with these viral markers were excluded from the preregistration trials. Likelihood score: E* (unlikely cause of idiosyncratic clinically apparent liver injury but is a potential cause of reactivation of hepatitis B). Deuruxolitinib had a similar incidence of AEs across groups and was generally well tolerated. Headache, acne, and increased blood creatine phosphokinase occurred in ≥5% of patients in both deuruxolitinib groups, while serious AEs were uncommon (and only 2 were considered by the study investigator to be potentially related to the study drug). Few treatment discontinuations occurred due to AEs, and no myocardial infarction, stroke, or thromboembolic events occurred. Herpes zoster was rare.[3] |
| References |
[1]. Treatment of hair loss disorders with deuterated jak inhibitors. Patent WO2017192905A1. [2]. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019 Feb;53(2):211-216. [3]. Efficacy and safety of deuruxolitinib, an oral selective Janus kinase inhibitor, in adults with alopecia areata: Results from the Phase 3 randomized, controlled trial (THRIVE-AA1). J Am Acad Dermatol. 2024 Nov;91(5):880-888. |
| Additional Infomation |
Deuruxolitinib is a deuterated form of [ruxolitinib] that selectively inhibits Janus kinases (JAK) JAK1 and JAK2. Deuteration allows the drug to circumvent extensive oxidative metabolism around the cyclopentyl ring, which increases the duration of the pharmacological activity of deuruxolitinib. On July 26, 2024, deuruxolitinib was approved by the FDA for the treatment of severe alopecia areata. Alopecia areata is an autoimmune condition that attacks the hair follicles and leads to unpredictable hair loss in the scalp and other areas of the body. The Janus kinase (JAK) signal transducer and activator of transcription (STAT) pathway has been implicated in the pathophysiology of alopecia areata, as it regulates the expression of inflammatory mediators. Deuruxolitinib works to block the inflammatory responses caused by JAKs.
Deuruxolitinib is a Janus Kinase Inhibitor. The mechanism of action of deuruxolitinib is as a Janus Kinase Inhibitor, and Breast Cancer Resistance Protein Inhibitor, and Bile Salt Export Pump Inhibitor, and Organic Anion Transporter 3 Inhibitor, and Multidrug and Toxin Extrusion Transporter 2 K Inhibitor. |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.1806 mL | 15.9028 mL | 31.8056 mL | |
| 5 mM | 0.6361 mL | 3.1806 mL | 6.3611 mL | |
| 10 mM | 0.3181 mL | 1.5903 mL | 3.1806 mL |