INCB3284 mesylate | CAS#887401-93-6 | 887401-92-5 | hCCR2 Antagonist

MedKoo Cat#: 526773 | Name: INCB3284 mesylate

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

INCB3284 is a potent, selective, and orally bioavailable hCCR2 Antagonist. INCB3284 exhibited an IC50 of 3.7 nM in antagonism of monocyte chemoattractant protein-1 binding to hCCR2, an IC50 of 4.7 nM in antagonism of chemotaxis activity, an IC50 of 84 μM in inhibition of the hERG potassium current, a free fraction of 58% in protein binding, high selectivity over other chemokine receptors and G-protein-coupled receptors, and acceptable oral bioavailability in rodents and primates. In human clinical trials, INCB3284 exhibited a pharmacokinetic profile suitable for once-a-day dosing (T 1/2 = 15 h).

Chemical Structure

INCB3284 mesylate

CAS#887401-93-6 (mesylate);

Theoretical Analysis

MedKoo Cat#: 526773

Name: INCB3284 mesylate

CAS#: 887401-93-6 (mesylate);

Chemical Formula: C28H39F3N4O10S2

Exact Mass:

Molecular Weight: 712.75

Elemental Analysis: C, 47.18; H, 5.52; F, 8.00; N, 7.86; O, 22.45; S, 9.00

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 300.00	2 Weeks
10mg	USD 550.00	2 Weeks

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Related CAS #

887401-92-5 (free base).

Synonym

INCB3284; INCB 3284; INCB-3284; INCB3284 mesylate; INCB3284 dimesylate.

IUPAC/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

InChi Key

PNPNUHKICDECDH-FBLZNNLISA-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

SMILES Code

O[C@]1(C2=CN=C(OC)C=C2)CC[C@@H](N3C[C@H](NC(CNC(C4=CC(C(F)(F)F)=CC=C4)=O)=O)CC3)CC1.CS(=O)(O)=O.CS(=O)(O)=O

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

INCB 3284 dimesylate is a potent, selective and orally bioavailable human CCR2 antagonist, inhibiting monocyte chemoattractant protein-1 binding to hCCR2, with an IC50 of 3.7 nM. INCB 3284 dimesylate can be used in the research of acute liver failure.

In vitro activity:

INCB3284 is a potent hCCR2 antagonist with IC50 values of 3.7 nM in antagonism of MCP-1 binding to hCCR2 and 4.7 nM in antagonism of chemotaxis activity. It potently inhibited CCR2-mediated signaling events such as intracellular calcium mobilization and ERK phosphorylation with IC50 values of 6 and 2.6 nM, respectively. Cerep screens revealed that INCB3284 is a selective CCR2 inhibitor, showing no significant inhibitory activity at a concentration of 1 μM when tested against a panel of >50 ion channels, transporters, chemokine receptors including CCR1, CCR3, CCR5, CXCR3, and CXCR5, and additional GPCRs. Reference: ACS Med Chem Lett. 2011 Mar 31;2(6):450-4. https://pubmed.ncbi.nlm.nih.gov/24900329/

In vivo activity:

When resuscitation was performed until t = 300 minutes, INCB3284 reduced fluid requirements by 62% ± 6%, prevented from hemodynamic decompensation, reduced mortality from 50% with vehicle treatment to zero, and reduced overall tissue wet-weight/dry-weight ratios in rats. Reference: Crit Care Explor. 2022 May 18;4(5):e0701. https://pubmed.ncbi.nlm.nih.gov/35620770/

	Solvent	mg/mL	mM
Solubility
	DMF	11.0	15.43
	DMSO	57.2	80.24
	PBS (pH 7.2)	5.0	7.02
	Water	71.3	100.00

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 712.75 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Xi S, Zheng X, Li X, Jiang Y, Wu Y, Gong J, Jie Y, Li Z, Cao J, Sha L, Zhang M, Chong Y. Activated Hepatic Stellate Cells Induce Infiltration and Formation of CD163+ Macrophages via CCL2/CCR2 Pathway. Front Med (Lausanne). 2021 Feb 5;8:627927. doi: 10.3389/fmed.2021.627927. PMID: 33614685; PMCID: PMC7893116. 2. Xue CB, Feng H, Cao G, Huang T, Glenn J, Anand R, Meloni D, Zhang K, Kong L, Wang A, Zhang Y, Zheng C, Xia M, Chen L, Tanaka H, Han Q, Robinson DJ, Modi D, Storace L, Shao L, Sharief V, Li M, Galya LG, Covington M, Scherle P, Diamond S, Emm T, Yeleswaram S, Contel N, Vaddi K, Newton R, Hollis G, Friedman S, Metcalf B. Discovery of INCB3284, a Potent, Selective, and Orally Bioavailable hCCR2 Antagonist. ACS Med Chem Lett. 2011 Mar 31;2(6):450-4. doi: 10.1021/ml200030q. PMID: 24900329; PMCID: PMC4018154. 3. DeSantis AJ, Weche M, Enten GA, Gao X, Majetschak M. The Chemokine (C-C Motif) Receptor 2 Antagonist INCB3284 Reduces Fluid Requirements and Protects From Hemodynamic Decompensation During Resuscitation From Hemorrhagic Shock. Crit Care Explor. 2022 May 18;4(5):e0701. doi: 10.1097/CCE.0000000000000701. PMID: 35620770; PMCID: PMC9119637. 4. McMillin M, Frampton G, Thompson M, Galindo C, Standeford H, Whittington E, Alpini G, DeMorrow S. Neuronal CCL2 is upregulated during hepatic encephalopathy and contributes to microglia activation and neurological decline. J Neuroinflammation. 2014 Jul 10;11:121. doi: 10.1186/1742-2094-11-121. PMID: 25012628; PMCID: PMC4128607.

In vitro protocol:

In vivo protocol:

1. DeSantis AJ, Weche M, Enten GA, Gao X, Majetschak M. The Chemokine (C-C Motif) Receptor 2 Antagonist INCB3284 Reduces Fluid Requirements and Protects From Hemodynamic Decompensation During Resuscitation From Hemorrhagic Shock. Crit Care Explor. 2022 May 18;4(5):e0701. doi: 10.1097/CCE.0000000000000701. PMID: 35620770; PMCID: PMC9119637. 2. McMillin M, Frampton G, Thompson M, Galindo C, Standeford H, Whittington E, Alpini G, DeMorrow S. Neuronal CCL2 is upregulated during hepatic encephalopathy and contributes to microglia activation and neurological decline. J Neuroinflammation. 2014 Jul 10;11:121. doi: 10.1186/1742-2094-11-121. PMID: 25012628; PMCID: PMC4128607.

1: McMillin M, Frampton G, Thompson M, Galindo C, Standeford H, Whittington E, Alpini G, DeMorrow S. Neuronal CCL2 is upregulated during hepatic encephalopathy and contributes to microglia activation and neurological decline. J Neuroinflammation. 2014 Jul 10;11:121. doi: 10.1186/1742-2094-11-121. PubMed PMID: 25012628; PubMed Central PMCID: PMC4128607. 2: Zhou X, Chen K, Lei H, Sun Z. Klotho gene deficiency causes salt-sensitive hypertension via monocyte chemotactic protein-1/CC chemokine receptor 2-mediated inflammation. J Am Soc Nephrol. 2015 Jan;26(1):121-32. doi: 10.1681/ASN.2013101033. Epub 2014 Jun 5. PubMed PMID: 24904083; PubMed Central PMCID: PMC4279730. 3: Xue CB, Feng H, Cao G, Huang T, Glenn J, Anand R, Meloni D, Zhang K, Kong L, Wang A, Zhang Y, Zheng C, Xia M, Chen L, Tanaka H, Han Q, Robinson DJ, Modi D, Storace L, Shao L, Sharief V, Li M, Galya LG, Covington M, Scherle P, Diamond S, Emm T, Yeleswaram S, Contel N, Vaddi K, Newton R, Hollis G, Friedman S, Metcalf B. Discovery of INCB3284, a Potent, Selective, and Orally Bioavailable hCCR2 Antagonist. ACS Med Chem Lett. 2011 Mar 31;2(6):450-4. doi: 10.1021/ml200030q. eCollection 2011 Jun 9. PubMed PMID: 24900329; PubMed Central PMCID: PMC4018154.