INCB 3284 dimesylate is a potent and specific human CCR2 antagonist that can inhibit/disrupts the binding of monocyte chemoattractant protein 1 to hCCR2 with IC50 of 3.7 nM. INCB 3284 dimesylate may be utilized in study/research of acute liver failure.

Physicochemical Properties

Molecular Formula	C26H31N4O4F3.2[CH4O3S]
Molecular Weight	712.7532
Exact Mass	712.205
CAS #	887401-93-6
Related CAS #	INCB 3284;887401-92-5
PubChem CID	11679268
Appearance	Colorless to light yellow ointment
LogP	4.749
Hydrogen Bond Donor Count	5
Hydrogen Bond Acceptor Count	15
Rotatable Bond Count	7
Heavy Atom Count	47
Complexity	883
Defined Atom Stereocenter Count	1
SMILES	O=C(NCC(N[C@H]1CN([C@H]2CC[C@](C3=CC=C(OC)N=C3)(O)CC2)CC1)=O)C4=CC=CC(C(F)(F)F)=C4.CS(=O)(O)=O.CS(=O)(O)=O
InChi Key	PNPNUHKICDECDH-SEBNIYPMSA-N
InChi Code	InChI=1S/C26H31F3N4O4.2CH4O3S/c1-37-23-6-5-19(14-30-23)25(36)10-7-21(8-11-25)33-12-9-20(16-33)32-22(34)15-31-24(35)17-3-2-4-18(13-17)26(27,28)29;2*1-5(2,3)4/h2-6,13-14,20-21,36H,7-12,15-16H2,1H3,(H,31,35)(H,32,34);2*1H3,(H,2,3,4)/t20-,21?,25?;;/m1../s1
Chemical Name	N-(2-(((R)-1-((1r,4R)-4-hydroxy-4-(6-methoxypyridin-3-yl)cyclohexyl)pyrrolidin-3-yl)amino)-2-oxoethyl)-3-(trifluoromethyl)benzamide dimethanesulfonate
Synonyms	INCB3284 mesylateINCB3284 INCB3284 dimesylate INCB 3284 INCB-3284
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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
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

ln Vitro	With an IC50 of 3.7 nM, INCB 3284 dimesylate, an orally accessible, five-selective human CCR2 antagonist, prevents monocyte chemoattractant protein-1 from binding to hCCR2. Moreover, INCB 3284 demonstrated an IC50 of 84 μM when it came to suppressing hERG potassium currents and 4.7 nM when it came to opposing chemotactic activity. At a dose of 1 μM, INCB 3284 did not exhibit any effect on GPCRs, including CCR1, CCR3, CCR5, CXCR3, and CXCR5. Furthermore, with IC50 values of 6 and 2.6 nM, respectively, INCB 3284 can potently block CCR2-mediated signal transduction processes, such as intracellular calcium mobilization and ERK phosphorylation [1].
ln Vivo	By blocking CCR2, INCB 3284 (1 mg/kg/day, i.p.) lessens microglial activation and liver damage in mice given AOM. INCB 3284 was also found to dramatically decrease proinflammatory cytokine production, G protein signaling pathway activity, and the ratio of pERK1/2 to tERK1/2 in cortical lysates of mice given azoxymethane [2].
References	[1]. Discovery of INCB3284, a Potent, Selective, and Orally Bioavailable hCCR2 Antagonist. ACS Med Chem Lett. 2011 Mar 31;2(6):450-4. [2]. Neuronal CCL2 is upregulated during hepatic encephalopathy and contributes to microglia activation and neurological decline. J Neuroinflammation. 2014 Jul 10;11:121.

Solubility Data

Solubility (In Vitro)

DMSO : ≥ 83.3 mg/mL (~116.87 mM)

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	1.4030 mL	7.0151 mL	14.0302 mL
	5 mM	0.2806 mL	1.4030 mL	2.8060 mL
	10 mM	0.1403 mL	0.7015 mL	1.4030 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.