JNJ-49095397 (RV568) is an inhaled narrow-spectrum kinase inhibitor (NSKI) that can inhibit the α and γ isoforms of p38 MAPK. JNJ-49095397 also inhibits the SRC kinase family, especially hematopoietic kinase (HCK), showing strong anti-inflammatory effects and may be utilized in the research of chronic obstructive pulmonary disease (COPD) and asthma.

Physicochemical Properties

Molecular Formula	C34H36N6O4
Exact Mass	592.279
CAS #	1220626-82-3
PubChem CID	45109868
Appearance	Off-white to gray solid powder
Density	1.2±0.1 g/cm3
Boiling Point	738.0±60.0 °C at 760 mmHg
Flash Point	400.1±32.9 °C
Vapour Pressure	0.0±2.4 mmHg at 25°C
Index of Refraction	1.627
LogP	6.5
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	10
Heavy Atom Count	44
Complexity	937
Defined Atom Stereocenter Count	0
InChi Key	RTDCVLCTBQDLBW-UHFFFAOYSA-N
InChi Code	InChI=1S/C34H36N6O4/c1-22-10-12-24(13-11-22)40-31(19-29(39-40)34(2,3)4)38-33(42)36-27-14-15-28(26-9-7-6-8-25(26)27)44-20-23-16-17-35-30(18-23)37-32(41)21-43-5/h6-19H,20-21H2,1-5H3,(H,35,37,41)(H2,36,38,42)
Chemical Name	N-[4-[[4-[[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxymethyl]pyridin-2-yl]-2-methoxyacetamide
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	p38α p38γ Haematopoietic Kinase (HCK)
ln Vitro	In PBMCs and d-U937 cells, JNJ-49095397 (RV568) (1 pg-1 μg/mL; 4 h) suppresses the production of CXCL8 triggered by LPS [1]. TNFα-induced production of interleukin (IL)-6 and CXCL8 is inhibited in a concentration-dependent manner by JNJ-49095397 (1 μg-1 g/mL; 4 h) [1].
ln Vivo	A mouse model of LPS-induced neutrophil buildup shows anti-inflammatory effect when JNJ-49095397 (RV568) (1–20 μg/mouse; intratracheal; once) is administered[1].
Animal Protocol	Animal/Disease Models: Nonfasted Balb/c mice, LPS-induced neutrophil accumulation model[1] Doses: 1, 4 and 20 μg/mouse Route of Administration: Intracheal administration, 2, 8 or 12 h prior to LPS inhalation Experimental Results: Prevented the accumulation of neutrophils in the BAL fluid. Dramatically inhibited neutrophil accumulation when administered up to 8 h prior to LPS inhalation.
References	[1]. RV568, a narrow-spectrum kinase inhibitor with p38 MAPK-α and -γ selectivity, suppresses COPD inflammation. Eur Respir J. 2017 Oct 26;50(4):1700188.

Solubility Data

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.)