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MedKoo Cat#: 526774 | Name: INCB3344 free base
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Description:

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

INCB3344 is a potent and selective antagonist of CCR2 receptor with IC(50) values of 5.1 nM (hCCR2) and 9.5 nM (mCCR2) in binding antagonism and 3.8 nM (hCCR2) and 7.8 nM (mCCR2) in antagonism of chemotaxis activity. INCB3344 exhibited >100-fold selectivity over other homologous chemokine receptors, a free fraction of 24% in human serum and 15% in mouse serum, and an oral bioavailability of 47% in mice, suitable as a tool compound for target validation in rodent models.

Chemical Structure

INCB3344 free base
INCB3344 free base
CAS#1262238-11-8 (free base)

Theoretical Analysis

MedKoo Cat#: 526774

Name: INCB3344 free base

CAS#: 1262238-11-8 (free base)

Chemical Formula: C29H34F3N3O6

Exact Mass: 0.0000

Molecular Weight: 577.60

Elemental Analysis: C, 60.30; H, 5.93; F, 9.87; N, 7.28; O, 16.62

Price and Availability

Size Price Availability Quantity
5mg USD 450.00 2 Weeks
10mg USD 800.00 2 Weeks
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Related CAS #
709018-37-1 (isomers) 1262238-11-8 (free base)
Synonym
INCB3344; INCB-3344; INCB 3344.
IUPAC/Chemical Name
N-(2-(((3R,4R)-1-((1s,4S)-4-(benzo[d][1,3]dioxol-5-yl)-4-hydroxycyclohexyl)-4-ethoxypyrrolidin-3-yl)amino)-2-oxoethyl)-3-(trifluoromethyl)benzamide
InChi Key
MZEOSVPWMSEFPW-OXKSBSDWSA-N
InChi Code
InChI=1S/C29H34F3N3O6/c1-2-39-25-16-35(21-8-10-28(38,11-9-21)19-6-7-23-24(13-19)41-17-40-23)15-22(25)34-26(36)14-33-27(37)18-4-3-5-20(12-18)29(30,31)32/h3-7,12-13,21-22,25,38H,2,8-11,14-17H2,1H3,(H,33,37)(H,34,36)/t21-,22-,25-,28+/m1/s1
SMILES Code
O=C(NCC(N[C@@H]1CN([C@H]2CC[C@](O)(C3=CC=C(OCO4)C4=C3)CC2)C[C@H]1OCC)=O)C5=CC=CC(C(F)(F)F)=C5
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:
INCB3344 is a potent, selective and orally bioavailable CCR2 antagonist with IC50 values of 5.1 nM (hCCR2) and 9.5 nM (mCCR2) in binding antagonism and 3.8 nM (hCCR2) and 7.8 nM (mCCR2) in antagonism of chemotaxis activity.
In vitro activity:
In vitro, INCB3344 inhibits the binding of CCL2 to mouse monocytes with nanomolar potency (IC(50) = 10 nM) and displays dose-dependent inhibition of CCL2-mediated functional responses such as ERK phosphorylation and chemotaxis with similar potency. Reference: J Immunol. 2005 Oct 15;175(8):5370-8. https://pubmed.ncbi.nlm.nih.gov/16210643/
In vivo activity:
The number of F4/80 positive cells was substantially lower in INCB3344-treated mice than in vehicle-treated mice in both choroid- RPE flat mounts (Fig. 2A) and sections (Fig. 3A). Reference: PLoS One. 2011;6(12):e28933. https://pubmed.ncbi.nlm.nih.gov/22205983/
Solvent mg/mL mM
Solubility
DMSO 220.0 380.89
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 577.60 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.

Recalculate based on batch purity %
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. Belkouch M, Dansereau MA, Réaux-Le Goazigo A, Van Steenwinckel J, Beaudet N, Chraibi A, Melik-Parsadaniantz S, Sarret P. The chemokine CCL2 increases Nav1.8 sodium channel activity in primary sensory neurons through a Gβγ-dependent mechanism. J Neurosci. 2011 Dec 14;31(50):18381-90. doi: 10.1523/JNEUROSCI.3386-11.2011. PMID: 22171040; PMCID: PMC6623900. 2. Brodmerkel CM, Huber R, Covington M, Diamond S, Hall L, Collins R, Leffet L, Gallagher K, Feldman P, Collier P, Stow M, Gu X, Baribaud F, Shin N, Thomas B, Burn T, Hollis G, Yeleswaram S, Solomon K, Friedman S, Wang A, Xue CB, Newton RC, Scherle P, Vaddi K. Discovery and pharmacological characterization of a novel rodent-active CCR2 antagonist, INCB3344. J Immunol. 2005 Oct 15;175(8):5370-8. doi: 10.4049/jimmunol.175.8.5370. PMID: 16210643. 3. Ito S, Nakashima H, Ishikiriyama T, Nakashima M, Yamagata A, Imakiire T, Kinoshita M, Seki S, Kumagai H, Oshima N. Effects of a CCR2 antagonist on macrophages and Toll-like receptor 9 expression in a mouse model of diabetic nephropathy. Am J Physiol Renal Physiol. 2021 Dec 1;321(6):F757-F770. doi: 10.1152/ajprenal.00191.2021. Epub 2021 Nov 1. PMID: 34719947. 4. Xie P, Kamei M, Suzuki M, Matsumura N, Nishida K, Sakimoto S, Sakaguchi H, Nishida K. Suppression and regression of choroidal neovascularization in mice by a novel CCR2 antagonist, INCB3344. PLoS One. 2011;6(12):e28933. doi: 10.1371/journal.pone.0028933. Epub 2011 Dec 19. PMID: 22205983; PMCID: PMC3242774.
In vitro protocol:
1. Belkouch M, Dansereau MA, Réaux-Le Goazigo A, Van Steenwinckel J, Beaudet N, Chraibi A, Melik-Parsadaniantz S, Sarret P. The chemokine CCL2 increases Nav1.8 sodium channel activity in primary sensory neurons through a Gβγ-dependent mechanism. J Neurosci. 2011 Dec 14;31(50):18381-90. doi: 10.1523/JNEUROSCI.3386-11.2011. PMID: 22171040; PMCID: PMC6623900. 2. Brodmerkel CM, Huber R, Covington M, Diamond S, Hall L, Collins R, Leffet L, Gallagher K, Feldman P, Collier P, Stow M, Gu X, Baribaud F, Shin N, Thomas B, Burn T, Hollis G, Yeleswaram S, Solomon K, Friedman S, Wang A, Xue CB, Newton RC, Scherle P, Vaddi K. Discovery and pharmacological characterization of a novel rodent-active CCR2 antagonist, INCB3344. J Immunol. 2005 Oct 15;175(8):5370-8. doi: 10.4049/jimmunol.175.8.5370. PMID: 16210643.
In vivo protocol:
1. Ito S, Nakashima H, Ishikiriyama T, Nakashima M, Yamagata A, Imakiire T, Kinoshita M, Seki S, Kumagai H, Oshima N. Effects of a CCR2 antagonist on macrophages and Toll-like receptor 9 expression in a mouse model of diabetic nephropathy. Am J Physiol Renal Physiol. 2021 Dec 1;321(6):F757-F770. doi: 10.1152/ajprenal.00191.2021. Epub 2021 Nov 1. PMID: 34719947. 2. Xie P, Kamei M, Suzuki M, Matsumura N, Nishida K, Sakimoto S, Sakaguchi H, Nishida K. Suppression and regression of choroidal neovascularization in mice by a novel CCR2 antagonist, INCB3344. PLoS One. 2011;6(12):e28933. doi: 10.1371/journal.pone.0028933. Epub 2011 Dec 19. PMID: 22205983; PMCID: PMC3242774.
1: Chu HX, Kim HA, Lee S, Broughton BR, Drummond GR, Sobey CG. Evidence of CCR2-independent transmigration of Ly6C(hi) monocytes into the brain after permanent cerebral ischemia in mice. Brain Res. 2016 Apr 15;1637:118-27. doi: 10.1016/j.brainres.2016.02.030. Epub 2016 Feb 24. PubMed PMID: 26921777. 2: Moore JP, Vinh A, Tuck KL, Sakkal S, Krishnan SM, Chan CT, Lieu M, Samuel CS, Diep H, Kemp-Harper BK, Tare M, Ricardo SD, Guzik TJ, Sobey CG, Drummond GR. M2 macrophage accumulation in the aortic wall during angiotensin II infusion in mice is associated with fibrosis, elastin loss, and elevated blood pressure. Am J Physiol Heart Circ Physiol. 2015 Sep;309(5):H906-17. doi: 10.1152/ajpheart.00821.2014. Epub 2015 Jun 12. PubMed PMID: 26071547. 3: Chu HX, Broughton BR, Kim HA, Lee S, Drummond GR, Sobey CG. Evidence That Ly6C(hi) Monocytes are Protective in Acute Ischemic Stroke by Promoting M2 Macrophage Polarization. Stroke. 2015 Jul;46(7):1929-37. doi: 10.1161/STROKEAHA.115.009426. Epub 2015 May 21. PubMed PMID: 25999385. 4: Zweemer AJ, Bunnik J, Veenhuizen M, Miraglia F, Lenselink EB, Vilums M, de Vries H, Gibert A, Thiele S, Rosenkilde MM, IJzerman AP, Heitman LH. Discovery and mapping of an intracellular antagonist binding site at the chemokine receptor CCR2. Mol Pharmacol. 2014 Oct;86(4):358-68. doi: 10.1124/mol.114.093328. Epub 2014 Jul 14. PubMed PMID: 25024169. 5: Zhao R, Pei GX, Cong R, Zhang H, Zang CW, Tian T. PKC-NF-κB are involved in CCL2-induced Nav1.8 expression and channel function in dorsal root ganglion neurons. Biosci Rep. 2014 Jun 18;34(3). pii: e00111. doi: 10.1042/BSR20140005. PubMed PMID: 24724624; PubMed Central PMCID: PMC4062041. 6: Shahlaei M, Fassihi A, Papaleo E, Pourfarzam M. Molecular dynamics simulation of chemokine receptors in lipid bilayer: a case study on C-C chemokine receptor type 2. Chem Biol Drug Des. 2013 Nov;82(5):534-45. doi: 10.1111/cbdd.12179. Epub 2013 Aug 10. PubMed PMID: 23930622. 7: Dauvergne C, Molet J, Reaux-Le Goazigo A, Mauborgne A, Mélik-Parsadaniantz S, Boucher Y, Pohl M. Implication of the chemokine CCL2 in trigeminal nociception and traumatic neuropathic orofacial pain. Eur J Pain. 2014 Mar;18(3):360-75. doi: 10.1002/j.1532-2149.2013.00377.x. Epub 2013 Aug 5. PubMed PMID: 23918315. 8: Zweemer AJ, Nederpelt I, Vrieling H, Hafith S, Doornbos ML, de Vries H, Abt J, Gross R, Stamos D, Saunders J, Smit MJ, Ijzerman AP, Heitman LH. Multiple binding sites for small-molecule antagonists at the CC chemokine receptor 2. Mol Pharmacol. 2013 Oct;84(4):551-61. doi: 10.1124/mol.113.086850. Epub 2013 Jul 22. PubMed PMID: 23877010. 9: Chan CT, Moore JP, Budzyn K, Guida E, Diep H, Vinh A, Jones ES, Widdop RE, Armitage JA, Sakkal S, Ricardo SD, Sobey CG, Drummond GR. Reversal of vascular macrophage accumulation and hypertension by a CCR2 antagonist in deoxycorticosterone/salt-treated mice. Hypertension. 2012 Nov;60(5):1207-12. doi: 10.1161/HYPERTENSIONAHA.112.201251. Epub 2012 Oct 1. PubMed PMID: 23033370. 10: Xie P, Kamei M, Suzuki M, Matsumura N, Nishida K, Sakimoto S, Sakaguchi H, Nishida K. Suppression and regression of choroidal neovascularization in mice by a novel CCR2 antagonist, INCB3344. PLoS One. 2011;6(12):e28933. doi: 10.1371/journal.pone.0028933. Epub 2011 Dec 19. PubMed PMID: 22205983; PubMed Central PMCID: PMC3242774. 11: Belkouch M, Dansereau MA, Réaux-Le Goazigo A, Van Steenwinckel J, Beaudet N, Chraibi A, Melik-Parsadaniantz S, Sarret P. The chemokine CCL2 increases Nav1.8 sodium channel activity in primary sensory neurons through a Gβγ-dependent mechanism. J Neurosci. 2011 Dec 14;31(50):18381-90. doi: 10.1523/JNEUROSCI.3386-11.2011. PubMed PMID: 22171040. 12: Van Steenwinckel J, Reaux-Le Goazigo A, Pommier B, Mauborgne A, Dansereau MA, Kitabgi P, Sarret P, Pohl M, Mélik Parsadaniantz S. CCL2 released from neuronal synaptic vesicles in the spinal cord is a major mediator of local inflammation and pain after peripheral nerve injury. J Neurosci. 2011 Apr 13;31(15):5865-75. doi: 10.1523/JNEUROSCI.5986-10.2011. PubMed PMID: 21490228. 13: Xue CB, Wang A, Meloni D, Zhang K, Kong L, Feng H, Glenn J, Huang T, Zhang Y, Cao G, Anand R, Zheng C, Xia M, Han Q, Robinson DJ, Storace L, Shao L, Li M, Brodmerkel CM, Covington M, Scherle P, Diamond S, Yeleswaram S, Vaddi K, Newton R, Hollis G, Friedman S, Metcalf B. Discovery of INCB3344, a potent, selective and orally bioavailable antagonist of human and murine CCR2. Bioorg Med Chem Lett. 2010 Dec 15;20(24):7473-8. doi: 10.1016/j.bmcl.2010.10.020. Epub 2010 Oct 13. PubMed PMID: 21036044. 14: Shin N, Baribaud F, Wang K, Yang G, Wynn R, Covington MB, Feldman P, Gallagher KB, Leffet LM, Lo YY, Wang A, Xue CB, Newton RC, Scherle PA. Pharmacological characterization of INCB3344, a small molecule antagonist of human CCR2. Biochem Biophys Res Commun. 2009 Sep 18;387(2):251-5. doi: 10.1016/j.bbrc.2009.06.135. Epub 2009 Jul 1. PubMed PMID: 19576173. 15: Dansereau MA, Gosselin RD, Pohl M, Pommier B, Mechighel P, Mauborgne A, Rostene W, Kitabgi P, Beaudet N, Sarret P, Melik-Parsadaniantz S. Spinal CCL2 pronociceptive action is no longer effective in CCR2 receptor antagonist-treated rats. J Neurochem. 2008 Jul;106(2):757-69. doi: 10.1111/j.1471-4159.2008.05429.x. Epub 2008 Apr 17. PubMed PMID: 18419759. 16: Brodmerkel CM, Huber R, Covington M, Diamond S, Hall L, Collins R, Leffet L, Gallagher K, Feldman P, Collier P, Stow M, Gu X, Baribaud F, Shin N, Thomas B, Burn T, Hollis G, Yeleswaram S, Solomon K, Friedman S, Wang A, Xue CB, Newton RC, Scherle P, Vaddi K. Discovery and pharmacological characterization of a novel rodent-active CCR2 antagonist, INCB3344. J Immunol. 2005 Oct 15;175(8):5370-8. PubMed PMID: 16210643.