BX-471 HCl | CAS# 288262-96-4 | CCR1 antagonist

MedKoo Cat#: 412191 | Name: BX-471 HCl

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Description:

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

BX-471, also known as ZK-811752, is a potent, selective non-peptide CCR1 antagonist (Ki = 1 nM for human CCR1). BX-471 exhibits 250-fold selectivity for CCR1 over CCR2, CCR5 and CXCR4. BX-471 was developed Berlex and its parent company, Schering AG. BX-471 is the lead in a series of non-peptide chemokine receptor 1 (CCR1) antagonists, for the potential treatment of autoimmune diseases, in particular multiple sclerosis (MS). In March 2000, BX-471 was undergoing phase I trials for the potential treatment of autoimmune diseases.

Chemical Structure

BX-471 HCl

CAS#288262-96-4 (HCl)

Theoretical Analysis

MedKoo Cat#: 412191

Name: BX-471 HCl

CAS#: 288262-96-4 (HCl)

Chemical Formula: C21H25Cl2FN4O3

Exact Mass: 434.1521

Molecular Weight: 471.35

Elemental Analysis: C, 53.51; H, 5.35; Cl, 15.04; F, 4.03; N, 11.89; O, 10.18

Price and Availability

Size	Price	Availability
25mg	USD 385.00	2 Weeks
50mg	USD 550.00	2 Weeks
100mg	USD 950.00	2 Weeks

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Related CAS #

217645-70-0 (free base) 288262-96-4 (HCl)

Synonym

BX-471 HCl; BX-471 hydrochloride, BX-471 free base; BX471; BX 471; ZK-811752; ZK 811752; ZK811752;

IUPAC/Chemical Name

(2R)-1-(((4-Chloro-2-(ureido)phenoxy)methyl)carbonyl)-2-methyl-4-(4-fluorobenzyl)piperazine hydrochloride

InChi Key

FRUCNQBAWUHKLS-PFEQFJNWSA-N

InChi Code

InChI=1S/C21H24ClFN4O3.ClH/c1-14-11-26(12-15-2-5-17(23)6-3-15)8-9-27(14)20(28)13-30-19-7-4-16(22)10-18(19)25-21(24)29;/h2-7,10,14H,8-9,11-13H2,1H3,(H3,24,25,29);1H/t14-;/m1./s1

SMILES Code

FC1=CC=C(C=C1)CN2C[C@@H](C)N(C(COC3=CC=C(Cl)C=C3NC(N)=O)=O)CC2.[H]Cl

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

>3 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

Instruction

View handling instruction

Preparing Stock Solutions

The following data is based on the product molecular weight 471.35 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

1: Feng S, Ju L, Shao Z, Grzanna M, Jia L, Liu M. Therapeutic Effect of C-C Chemokine Receptor Type 1 (CCR1) Antagonist BX471 on Allergic Rhinitis. J Inflamm Res. 2020 Jul 21;13:343-356. doi: 10.2147/JIR.S254717. PMID: 32801828; PMCID: PMC7398876. 2: Blázquez-Prieto J, López-Alonso I, Amado-Rodríguez L, Batalla-Solís E, González-López A, Albaiceta GM. Exposure to mechanical ventilation promotes tolerance to ventilator-induced lung injury by Ccl3 downregulation. Am J Physiol Lung Cell Mol Physiol. 2015 Oct 15;309(8):L847-56. doi: 10.1152/ajplung.00193.2015. Epub 2015 Aug 21. PMID: 26472813. 3: Gilchrist A, Gauntner TD, Fazzini A, Alley KM, Pyen DS, Ahn J, Ha SJ, Willett A, Sansom SE, Yarfi JL, Bachovchin KA, Mazzoni MR, Merritt JR. Identifying bias in CCR1 antagonists using radiolabelled binding, receptor internalization, β-arrestin translocation and chemotaxis assays. Br J Pharmacol. 2014 Nov;171(22):5127-38. doi: 10.1111/bph.12835. PMID: 24990525; PMCID: PMC4253460. 4: Ji HJ, Hu JF, Chen NH. [Advances in the study of small molecule antagonists of chemokine receptors as anti-asthma agents]. Yao Xue Xue Bao. 2011 Nov;46(11):1286-90. Chinese. PMID: 22260017. 5: Shahlaei M, Madadkar-Sobhani A, Fassihi A, Saghaie L. Exploring a model of a chemokine receptor/ligand complex in an explicit membrane environment by molecular dynamics simulation: the human CCR1 receptor. J Chem Inf Model. 2011 Oct 24;51(10):2717-30. doi: 10.1021/ci200261f. Epub 2011 Sep 28. PMID: 21910472. 6: Lebre MC, Vergunst CE, Choi IY, Aarrass S, Oliveira AS, Wyant T, Horuk R, Reedquist KA, Tak PP. Why CCR2 and CCR5 blockade failed and why CCR1 blockade might still be effective in the treatment of rheumatoid arthritis. PLoS One. 2011;6(7):e21772. doi: 10.1371/journal.pone.0021772. Epub 2011 Jul 1. PMID: 21747955; PMCID: PMC3128605. 7: Yang X, Walton W, Cook DN, Hua X, Tilley S, Haskell CA, Horuk R, Blackstock AW, Kirby SL. The chemokine, CCL3, and its receptor, CCR1, mediate thoracic radiation-induced pulmonary fibrosis. Am J Respir Cell Mol Biol. 2011 Jul;45(1):127-35. doi: 10.1165/rcmb.2010-0265OC. Epub 2010 Sep 24. PMID: 20870892; PMCID: PMC3145066. 8: Reuss R, Schreiber V, Klein A, Infante-Duarte C, Filippi M, Pabst W, Pohl C, Oschmann P. No significant effect of orally administered chemokine receptor 1 antagonist on intercellular adhesion molecule-3 expression in relapsing-- remitting multiple sclerosis patients. Mult Scler. 2010 Mar;16(3):366-9. doi: 10.1177/1352458509358188. Epub 2010 Jan 19. PMID: 20086017. 9: Djamali A, Samaniego M. Fibrogenesis in kidney transplantation: potential targets for prevention and therapy. Transplantation. 2009 Nov 27;88(10):1149-56. doi: 10.1097/TP.0b013e3181bcccea. PMID: 19935366; PMCID: PMC2784657. 10: Vandemeulebroecke M, Lembcke J, Wiesinger H, Sittner W, Lindemann S. Assessment of QT(c)-prolonging potential of BX471 in healthy volunteers. A 'thorough QT study' following ICH E14 using various QT(c) correction methods. Br J Clin Pharmacol. 2009 Sep;68(3):435-46. doi: 10.1111/j.1365-2125.2009.03460.x. PMID: 19740402; PMCID: PMC2766484. 11: Lange-Sperandio B, Trautmann A, Eickelberg O, Jayachandran A, Oberle S, Schmidutz F, Rodenbeck B, Hömme M, Horuk R, Schaefer F. Leukocytes induce epithelial to mesenchymal transition after unilateral ureteral obstruction in neonatal mice. Am J Pathol. 2007 Sep;171(3):861-71. doi: 10.2353/ajpath.2007.061199. Epub 2007 Aug 3. PMID: 17675578; PMCID: PMC1959504. 12: He M, Horuk R, Bhatia M. Treatment with BX471, a nonpeptide CCR1 antagonist, protects mice against acute pancreatitis-associated lung injury by modulating neutrophil recruitment. Pancreas. 2007 Mar;34(2):233-41. doi: 10.1097/mpa.0b013e31802e7598. PMID: 17312463. 13: Bayes M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2006 Dec;28(10):719-40. PMID: 17235418. 14: He M, Horuk R, Moochhala SM, Bhatia M. Treatment with BX471, a CC chemokine receptor 1 antagonist, attenuates systemic inflammatory response during sepsis. Am J Physiol Gastrointest Liver Physiol. 2007 Apr;292(4):G1173-80. doi: 10.1152/ajpgi.00420.2006. Epub 2007 Jan 18. Erratum in: Am J Physiol Gastrointest Liver Physiol. 2012 Jan;302(1):G194. PMID: 17234893. 15: Bedke J, Kiss E, Schaefer L, Behnes CL, Bonrouhi M, Gretz N, Horuk R, Diedrichs-Moehring M, Wildner G, Nelson PJ, Gröne HJ. Beneficial effects of CCR1 blockade on the progression of chronic renal allograft damage. Am J Transplant. 2007 Mar;7(3):527-37. doi: 10.1111/j.1600-6143.2006.01654.x. Epub 2007 Jan 4. PMID: 17229070. 16: Zipp F, Hartung HP, Hillert J, Schimrigk S, Trebst C, Stangel M, Infante- Duarte C, Jakobs P, Wolf C, Sandbrink R, Pohl C, Filippi M; CCR1 Antagonist Study Group. Blockade of chemokine signaling in patients with multiple sclerosis. Neurology. 2006 Nov 28;67(10):1880-3. doi: 10.1212/01.wnl.0000244420.68037.86. PMID: 17130431. 17: Menu E, De Leenheer E, De Raeve H, Coulton L, Imanishi T, Miyashita K, Van Valckenborgh E, Van Riet I, Van Camp B, Horuk R, Croucher P, Vanderkerken K. Role of CCR1 and CCR5 in homing and growth of multiple myeloma and in the development of osteolytic lesions: a study in the 5TMM model. Clin Exp Metastasis. 2006;23(5-6):291-300. doi: 10.1007/s10585-006-9038-6. Epub 2006 Nov 3. PMID: 17086356. 18: Vaidehi N, Schlyer S, Trabanino RJ, Floriano WB, Abrol R, Sharma S, Kochanny M, Koovakat S, Dunning L, Liang M, Fox JM, de Mendonça FL, Pease JE, Goddard WA 3rd, Horuk R. Predictions of CCR1 chemokine receptor structure and BX 471 antagonist binding followed by experimental validation. J Biol Chem. 2006 Sep 15;281(37):27613-20. doi: 10.1074/jbc.M601389200. Epub 2006 Jul 12. PMID: 16837468. 19: Horuk R. BX471: a CCR1 antagonist with anti-inflammatory activity in man. Mini Rev Med Chem. 2005 Sep;5(9):791-804. doi: 10.2174/1389557054867057. PMID: 16178722. 20: Kranz H, Wagner T. Effects of formulation and process variables on the release of a weakly basic drug from single unit extended release formulations. Eur J Pharm Biopharm. 2006 Jan;62(1):70-6. doi: 10.1016/j.ejpb.2005.07.003. Epub 2005 Sep 8. PMID: 16154330.