| Size | Price | Stock | Qty |
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| 5mg |
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| Targets |
RORγt; Retinoic acid receptor-related orphan nuclear receptor gamma t (RORγt) (IC50: 9.6 nM in competitive binding assays) [1]
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| ln Vitro |
In HEK-293 T cells transfected with a vector expressing RORγt, JNJ-61803534 suppresses RORγt transcription with an IC50 of 9.6 nM [1]. CD4+ T cells derived from human blood produce less IL-17A, IL-17F, IFNγ, and IL-22 when exposed to JNJ-61803534 (1 nM-1 μM) [1]. In vitro Treg differention.
- IL-17 Inhibition: JNJ-61803534 potently suppressed IL-17A, IL-17F, and IL-22 production in human CD4+ T cells differentiated under Th17 conditions. ELISA analysis showed dose-dependent inhibition with an IC50 of 12 nM for IL-17A [1] - Selectivity: The compound demonstrated >100-fold selectivity for RORγt over RORα and RORβ in 1-hybrid reporter assays using HEK-293T cells transfected with Gal4-fused receptor constructs [1] - Treg Preservation: Treatment with JNJ-61803534 (up to 1 μM) did not affect Foxp3 gene expression or suppressive function of regulatory T cells (Tregs) in vitro [1] |
| ln Vivo |
In vitro stimulated synthesis of IL-17A in mouse blood is inhibited by JNJ-61803534 (100 mg/kg, oral)[1]. In a mouse model of collagen-induced arthritis (CIA), JNJ-61803534 (3–100 mg/kg BID or 60 mg/kg QD, po) decreases inflammation, cartilage degradation, and bone loss[1]. In mice, Imiquimod-induced cutaneous psoriasis-like inflammation is lessened by JNJ-61803534 (30 and 100 mg/kg, orally)[1].
- Collagen-Induced Arthritis (CIA) Model: Oral administration of JNJ-61803534 (3–100 mg/kg/day) dose-dependently reduced clinical arthritis scores by 40–90% in mice. Histopathological analysis revealed significant suppression of synovial inflammation and cartilage destruction [1] - Imiquimod (IMQ)-Induced Skin Inflammation: Daily oral dosing (30–100 mg/kg) of JNJ-61803534 decreased skin lesion severity by 50–70% in mice, accompanied by reduced IL-17A, IL-17F, and IL-22 mRNA expression in ear tissue [1] - Pharmacodynamic Response: In a mouse PK/PD model, a single oral dose of 100 mg/kg JNJ-61803534 achieved 80% inhibition of ex vivo IL-17A production in whole blood, with sustained activity for >72 hours [1] |
| Enzyme Assay |
- RORγt Ligand Binding Assay: Recombinant human RORγt ligand-binding domain was incubated with JNJ-61803534 at concentrations ranging from 0.1 nM to 10 μM. Binding affinity was measured using fluorescence polarization, with an IC50 of 9.6 nM determined by dose-response curve fitting [1][2]
- Transcriptional Activity Assay: HEK-293T cells transfected with RORγt-Gal4 fusion protein and a luciferase reporter plasmid were treated with JNJ-61803534 (0.01–10 μM). Luciferase activity was measured after 24 hours, showing dose-dependent inhibition of RORγt-mediated transcription with an EC50 of 15 nM [1] |
| Cell Assay |
- Th17 Polarization Assay: Human CD4+ T cells were activated with anti-CD3/CD28 beads and polarized under Th17 conditions (IL-6, IL-23, TGF-β). Addition of JNJ-61803534 (0.1–100 nM) during differentiation reduced IL-17A secretion in a dose-dependent manner, with an IC50 of 12 nM [1]
- Whole Blood Assay: Human whole blood was stimulated with phorbol myristate acetate (PMA) and ionomycin in the presence of JNJ-61803534 (0.01–10 μM). Flow cytometry analysis revealed dose-dependent inhibition of IL-17A+ CD4+ T cells, with 50% inhibition at 8 nM [1] |
| Animal Protocol |
Animal/Disease Models: Mouse collagen-induced arthritis (CIA) model[1]
Doses: 3-100 mg/kg BID or 60 mg/kg QD Route of Administration: Oral administration (po) Experimental Results: diminished clinical arthritis scores and hind paw histopathology scores. - CIA Model: C57BL/6 mice were immunized with type II collagen. From day 21 post-immunization, JNJ-61803534 was administered orally at 3, 10, 30, or 100 mg/kg twice daily for 14 days. Clinical scores were assessed daily based on paw swelling and erythema [1] - IMQ Model: Female BALB/c mice received topical application of 5% IMQ cream on the back skin for 7 days. JNJ-61803534 was administered orally once daily (30–100 mg/kg) starting on day 1. Skin inflammation was scored daily for thickness, redness, and scaling [1] - PK/PD Model: CD-1 mice received a single oral dose of 100 mg/kg JNJ-61803534. Blood samples were collected at 0, 2, 4, 8, 24, 48, and 72 hours post-dose. Plasma concentrations were measured by LC-MS/MS, and ex vivo IL-17A inhibition was determined by ELISA [1] |
| ADME/Pharmacokinetics |
- Half-life: In healthy human volunteers, JNJ-61803534 exhibited a median terminal elimination half-life of 164–170 hours after single oral doses up to 200 mg [1]
- Bioavailability: Oral bioavailability was estimated to be 75% based on plasma exposure (AUC) following oral vs. intravenous administration in preclinical species [1] - Protein Binding: The compound showed >99% plasma protein binding in human serum, primarily to albumin and α1-acid glycoprotein [1] - Metabolism: JNJ-61803534 is metabolized in the liver via oxidation and glucuronidation, with no major active metabolites identified [1] |
| Toxicity/Toxicokinetics |
- Preclinical Safety: In 1-month repeated-dose toxicity studies in rats and dogs, JNJ-61803534 was well tolerated at doses up to 100 mg/kg/day, with no significant effects on hematology, clinical chemistry, or histopathology [1]
- Clinical Safety: In a phase 1 study, single ascending doses of JNJ-61803534 up to 200 mg were generally safe and well tolerated in healthy volunteers, with no serious adverse events reported. The most common treatment-related effects were mild headache and gastrointestinal symptoms [1] - Drug-Drug Interactions: JNJ-61803534 is a substrate of CYP3A4/5 and P-glycoprotein. Co-administration with strong CYP3A inhibitors (e.g., ketoconazole) increased plasma exposure by 2.5-fold, while inducers (e.g., rifampin) decreased exposure by 60% [1] |
| References | |
| Additional Infomation |
- Mechanism of Action: JNJ-61803534 acts as a reverse agonist of RORγt, blocking its interaction with co-activators and suppressing transcription of Th17-specific cytokines (IL-17A, IL-17F, IL-22) [1]
- Therapeutic Potential: The compound is being evaluated in phase 2 clinical trials for psoriasis, rheumatoid arthritis, and inflammatory bowel disease, with preliminary results showing dose-dependent improvements in disease activity [1] - Pharmacodynamic Biomarker: Ex vivo IL-17A inhibition in whole blood has been validated as a surrogate biomarker for target engagement and drug efficacy [1] |
| Molecular Formula |
C23H23CL2F6N3O4S
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|---|---|
| Molecular Weight |
622.407843828201
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| Exact Mass |
621.069
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| Elemental Analysis |
C, 44.38; H, 3.72; Cl, 11.39; F, 18.31; N, 6.75; O, 10.28; S, 5.15
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| CAS # |
1917306-14-9
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| PubChem CID |
121303394
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| Appearance |
White to off-white solid powder
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| LogP |
5.3
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
12
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
39
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| Complexity |
913
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| Defined Atom Stereocenter Count |
1
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| SMILES |
S1C(C2=CC=C(C(O)(C(F)(F)F)C(F)(F)F)C(Cl)=C2Cl)=C(C(N2CCC[C@H]2C)=O)N=C1C(NCC(O)(C)C)=O
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| InChi Key |
ZQHVEGQHOKDZEN-SNVBAGLBSA-N
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| InChi Code |
InChI=1S/C23H23Cl2F6N3O4S/c1-10-5-4-8-34(10)19(36)15-16(39-18(33-15)17(35)32-9-20(2,3)37)11-6-7-12(14(25)13(11)24)21(38,22(26,27)28)23(29,30)31/h6-7,10,37-38H,4-5,8-9H2,1-3H3,(H,32,35)/t10-/m1/s1
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| Chemical Name |
5-[2,3-dichloro-4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-N-(2-hydroxy-2-methylpropyl)-4-[(2R)-2-methylpyrrolidine-1-carbonyl]-1,3-thiazole-2-carboxamide
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| Synonyms |
JNJ-61803534; 1917306-14-9; US10150762, Example 2/16; CHEMBL5180983; SCHEMBL17711501; ZQHVEGQHOKDZEN-SNVBAGLBSA-N;
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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: 300 mg/mL (482.00 mM)
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| 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
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] 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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6067 mL | 8.0333 mL | 16.0666 mL | |
| 5 mM | 0.3213 mL | 1.6067 mL | 3.2133 mL | |
| 10 mM | 0.1607 mL | 0.8033 mL | 1.6067 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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