BX-471

• CAS: 217645-70-0
• Catalog Number: ACM217645700
• Category: Antagonists
• Molecular Weight: 434.89
• Molecular Formula: C21H24ClFN4O3
• Description: 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.
• Synonyms: BX471; BX 471; BX-471; ZK811752; ZK 811752; ZK-811752
• IUPAC Name: (R)-1-(5-chloro-2-(2-(4-(4-fluorobenzyl)-2-methylpiperazin-1-yl)-2-oxoethoxy)phenyl)urea
• Canonical SMILES: C[C@H]1N(C(COC2=CC=C(Cl)C=C2NC(N)=O)=O)CCN(CC3=CC=C(F)C=C3)C1
• InChI: InChI=1S/C21H24ClFN4O3/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)/t14-/m1/s1
• InChI Key: XQYASZNUFDVMFH-CQSZACIVSA-N
• Solubility: Soluble in DMSO, not in water
• Appearance: Solid powder
• Shelf Life: >2 years if stored properly
• Storage: Dry, dark and at 0-4 °C for short term (days to weeks) or -20 °C for long term (months to years).
• Alternative CAS: 217645-70-0 (free base); 288262-96-4 (HCl)
• Biological Target: Bx471 is a selective non-peptide CCR1 antagonist with Ki of 1 nM and exhibits 250-fold selectivity for CCR1 over CCR2, CCR5 and CXCR4.
• Drug Formulation: This drug may be formulated in DMSO
• Elemental Analysis: C, 58.00; H, 5.56; Cl, 8.15; F, 4.37; N, 12.88; O, 11.04
• Exact Mass: 434.1521
• HS Tariff Code: 2934.99.9001
• In Vitro Activity: Several well-studied CCR1 antagonists including AZD4818, BX471, CCX354, CP-481715, MLN-3897 and PS899877 were compared for their ability to inhibit binding of [125I]-CCL3 in vitro using membranes prepared from RPMI 8226 cells, a human multiple myeloma cell line that endogenously expresses CCR1. Using membranes from HEK_CCR1Gqi5 cells, it was confirmed that AZD-4818, BX471, CCX354, CP481715 and PS899877 are all potent inhibitors of [125I]-CCL3 binding Figure1;Table2). The compounds were then examined using membranes from RPMI 8226 cells (Figure 2, Table2;). Two compounds were equally potent with membranes from either cell line (BX471, PS899877). With HEK_CCR1 membranes it was found that MLN3879 > CCX354 ≥ AZD4818 > CP481715 = BX471 > PS899877 while with membranes from RPMI 8226 cells it was found that MLN3879 > BX471 > CP481715 ≥ PS899877 > AZD4818 > CCX354. Incubation of cells with AZD-4818, BX471, CCX354, MLN-3897 or PS899877 reduced CCL3-mediated receptor internalization and led to a dose-dependent recovery of surface CCR1 (Table 3; Figure2) although they all required higher concentrations than what was needed to block binding of I-CCL3. There appears to be biased antagonism with BX471, showing preference for reducing myeloma cell migration and β-arrestin translocation over CCR1 internalization or β-arrestin translocation.; Reference: Br J Pharmacol. 2014 Nov; 171(22): 5127-5138. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4253460/
• In Vivo Activity: In this study, the anti-inflammatory effect of BX471 was examined on ovalbumin (OVA)-induced AR mice model. The experiment utilized 30 female BALB/c mice, divided equally into three treatment groups: the normal group, the vehicle control group, and the BX471-treated group. The number of sneezes and the number of nasal-rubbing behaviors were different significantly between the normal group, the vehicle control group, and the BX471-treated group. As shown in Figure 2A, the number of sneezes significantly increased in the vehicle control group (20.9±1.5) compared with that of the normal group (1.1±0.7) during the 15 min period after the challenge (p<0.001). The number of sneezes in the BX471-treated group during the 15 min period after the challenge was 9.5±1.8, which was significantly attenuated compared with that of the vehicle control group (p<0.001) (Figure 2A); the number of nasalrubbing behaviors of the BX471-treated group was 107.6±14.0, which was significantly lower than that of the vehicle control group (p<0.05) (Figure 2B). The symptom scores indicate that BX471 treatment alleviated the symptoms of AR in mice. The BX471-treated group showed significantly lower levels of TNF-α in serum than the vehicle control group. Serum TNF-α levels were significantly (p<0.01) reduced in BX471 group compared with the vehicle control group (Figure 3B). The serum concentration of TNF-α in the vehicle control group was 27.54±4.39 pg/mL, whereas in the BX471-treated group that was 12.08±1.11 pg/mL (Figure 3B). Additionally, nasal expression levels of IL-4, IL-5, IL-13 were also significantly lower in BX471-treated group compared with the vehicle control group (Figure 5). Fold expression of IL-4 in the vehicle control group was 452.9±85.3 fold, whereas in the BX471treated group it was 38.5±15.7 fold (p<0.001). Overall, present study demonstrates that BX471 represents a promising therapeutic strategy against AR.; Reference: J Inflamm Res. 2020; 13: 343-356. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7398876/
• Shipping: 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.
• Stock Solution Storage: 0-4 °C for short term (days to weeks), or -20 °C for long term (months).