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.

Physicochemical Properties

Molecular Formula	C22H19N3O2S
Molecular Weight	389.470163583755
Exact Mass	389.12
Elemental Analysis	C, 67.84; H, 4.92; N, 10.79; O, 8.22; S, 8.23
CAS #	524923-88-4
PubChem CID	10110895
Appearance	Light yellow to yellow solid powder
LogP	4.85
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	5
Heavy Atom Count	28
Complexity	576
Defined Atom Stereocenter Count	0
SMILES	S1/C(=N/C2C=CC=CC=2)/N=C(C2C=CC=CC=2OC)N1C1C=CC=CC=1OC
InChi Key	XTHRTBCPBWJYRO-UHFFFAOYSA-N
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
Chemical Name	2,3-bis(2-methoxyphenyl)-N-phenyl-1,2,4-thiadiazol-5-imine
Synonyms	JNJ 10229570; JNJ-10229570; JNJ10229570; UNII-N9IX402L35
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	human MC1R ( IC50 = 270 nM ); human MC5R ( IC50 = 200 nM )
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].
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].
Animal Protocol	Mice: JNJ-10229570 (0.05%) or vehicle is topically applied for 30 days after human skin transplants onto SCID mice[1].
References	[1]. A melanocortin receptor 1 and 5 antagonist inhibits sebaceous gland differentiation and the production of sebum-specific lipids. J Dermatol Sci. 2011 Jul;63(1):23-32.

Solubility Data

Solubility (In Vitro)

DMSO: 62.5~78 mg/mL (160.5~200.3 mM

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.