| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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Purity: ≥98%
JNJ-10229570 is a novel, potent and selective antagonist of melanocortin receptor 1 (MC1R) and melanocortin receptor 5 (MC5R) with the potential to treat primary human sebaceous cells and for the treatment of acne and other sebaceous gland pathologies. JNJ-10229570 inhibits the lipid synthesis specific to sebum as well as the differentiation of sebaceous glands. Using IC50 values of 200 nM and 270 nM, respectively, JNJ-10229570 suppresses 125I-NDP-α-MSH binding to human MC1R and MC5R-expressing cells.
| Targets |
human MC1R ( IC50 = 270 nM ); human MC5R ( IC50 = 200 nM )
MC1R antagonist (IC₅₀ = 270 ± 120 nM) MC5R antagonist (IC₅₀ = 200 ± 50 nM) MC4R antagonist (IC₅₀ = 240 ± 170 nM)[1] |
|---|---|
| ln Vitro |
JNJ-10229570 inhibits the synthesis of sebaceous lipids in cultured primary human sebocytes in a dose-dependent manner. At IC50s of 270±120 and 200±50 nM, respectively, JNJ-7818369 inhibits the binding of 125I-NDP-α-MSH to human MC1R and MC5R expressing cells. The compound's free base form yields almost identical results. Both forms of the compound bind to MC4R equipotently, with IC50 values of 240±170 nM. Lipid granules are strongly inhibited in cells treated with JNJ-10229570 at 0.01 μM and completely inhibited at 0.05 μM [1].
JNJ-10229570 dose-dependently inhibited lipid production in primary human sebocytes induced by bovine pituitary extract (BPE) or cholera toxin (CT). At 0.01 μM, it significantly inhibited lipid granule formation, and complete inhibition was observed at 0.05–1 μM. It reduced squalene and cholesterol ester synthesis by ~58% and ~51%, respectively, while having minimal effect on triglycerides. Nile red assay showed ~40% reduction in total neutral lipid synthesis. It also reduced expression of the sebaceous differentiation marker epithelial membrane antigen (EMA) and decreased melanocortin 5 receptor (MC5R) mRNA expression in differentiated sebocytes.[1] |
| ln Vivo |
Topical application of JNJ-10229570 from human skins transplanted onto SCID mice leads to a significant reduction in the production of lipids specific to sebum, the size of the sebaceous glands, and the expression of the marker of sebaceous differentiation, epithelial-membrane antigen (EMA). Topical application of 0.05% JNJ-10229570 causes a noticeable decrease in newly-synthesised and steady-state sebum-specific lipids, while having less of an impact on cholesterol and triglycerides[1].
Topical application of 0.05% JNJ-10229570 on human skin xenografts transplanted onto SCID mice for 30 days significantly reduced sebum secretion, as shown by SEBUTAPE® analysis. HPTLC analysis of skin biopsies showed ~57% reduction in squalene, ~61% reduction in wax esters, and ~25% reduction in triglycerides. Histological examination revealed smaller sebaceous glands and reduced EMA staining, indicating inhibition of sebaceous cell differentiation.[1] |
| Enzyme Assay |
Radioligand binding assays were performed using cells overexpressing human MC1R, MC4R, or MC5R. The binding of ¹²⁵I-NDP-α-MSH was inhibited by JNJ-10229570 and its bromide salt form (JNJ-7818369), with IC₅₀ values calculated by non-linear least squares regression.[1]
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| Cell Assay |
Primary human sebocytes were cultured in three stages: growth, transition, and differentiation media, induced with BPE, CT, or forskolin. Cells were treated with JNJ-10229570 (0.01–1 μM) for 8 days. Lipid production was assessed by Nile red staining, HPTLC, and ¹⁴C-acetate labeling. Cytotoxicity was assessed using LDH assay, showing no toxicity up to 1 μM. Quantitative PCR was used to analyze melanocortin receptor expression.[1]
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| Animal Protocol |
Mice: JNJ-10229570 (0.05%) or vehicle is topically applied for 30 days after human skin transplants onto SCID mice[1].
Human facial skin was grafted onto male CB-17 SCID mice. After 3 months, xenografts were topically treated once daily, 5 days/week, for 30–34 days with 0.05% JNJ-10229570 or 5% flutamide dissolved in ethanol:propylene glycol (7:3). SEBUTAPE® was used to collect surface lipids. Biopsies were taken for HPTLC, histological (H&E), and immunohistochemical (EMA) analysis.[1] |
| References | |
| Additional Infomation |
JNJ-10229570 is a 2,3-diaryl-5-anilino-[1,2,4]thiadiazole compound that can act as a dual MC1R/MC5R antagonist. It can inhibit sebaceous cell differentiation and the production of sebum-specific lipids, suggesting its potential application value in the treatment of acne. It has no significant effect on MC1R-mediated skin pigmentation in melanocytes. [1]
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| Molecular Formula |
C22H19N3O2S
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|---|---|
| Molecular Weight |
389.470163583755
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| Exact Mass |
389.12
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| Elemental Analysis |
C, 67.84; H, 4.92; N, 10.79; O, 8.22; S, 8.23
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| CAS # |
524923-88-4
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| PubChem CID |
10110895
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
4.85
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
28
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| Complexity |
576
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S1/C(=N/C2C=CC=CC=2)/N=C(C2C=CC=CC=2OC)N1C1C=CC=CC=1OC
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| InChi Key |
XTHRTBCPBWJYRO-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H19N3O2S/c1-26-19-14-8-6-12-17(19)21-24-22(23-16-10-4-3-5-11-16)28-25(21)18-13-7-9-15-20(18)27-2/h3-15H,1-2H3
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| Chemical Name |
2,3-bis(2-methoxyphenyl)-N-phenyl-1,2,4-thiadiazol-5-imine
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| Synonyms |
JNJ 10229570; JNJ-10229570; JNJ10229570; UNII-N9IX402L35
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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: 62.5~78 mg/mL (160.5~200.3 mM
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.34 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. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.34 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5676 mL | 12.8380 mL | 25.6759 mL | |
| 5 mM | 0.5135 mL | 2.5676 mL | 5.1352 mL | |
| 10 mM | 0.2568 mL | 1.2838 mL | 2.5676 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT01492647 | Completed | Drug: JNJ 10229570-AAA 1.2% Drug: JNJ 10229570-AAA 3.6% |
Acne Vulgaris | Janssen Pharmaceutical K.K. | August 2011 | Phase 1 |
| NCT01494714 | Completed | Drug: JNJ 10229570-AAA 1.2% cream Drug: Petroleum jelly |
Healthy Volunteers | Janssen Pharmaceutical K.K. | August 2011 | Phase 1 |
| NCT01326780 | Completed | Drug: 1.2% JNJ 10229570-AAA Drug: 2.4% JNJ 10229570-AAA |
Acne Vulgaris | Bausch Health Americas, Inc. | March 31, 2011 | Phase 2 |
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