Balixafortide

• CAT Number: I003930
• CAS Number: 1051366-32-5
• Molecular Formula: C80H112N22O21S2
• Molecular Weight: 1782.029
• Purity: ≥95%
• Target: CXCR4 inhibitor
• Solubility: Soluble in DMSO, soluble in water.
• Storage: 0 - 4 °C for short term or -20 °C for long term
• InChI: InChI=1S/C80H112N22O21S2/c1-42(82)65(108)98-59-39-124-125-40-60(99-70(113)55(34-45-16-22-49(105)23-17-45)93-66(109)51(10-5-29-87-80(84)85)91-74(117)61-11-6-30-100(61)76(119)43(2)89-71(114)58(38-103)97-73(59)116)72(115)94-54(33-44-14-20-48(104)21-15-44)68(111)90-52(26-27-64(83)107)67(110)92-53(9-3-4-28-81)77(120)102-32-8-13-63(102)78(121)101-31-7-12-62(101)75(118)95-56(35-46-18-24-50(106)25-19-46)69(112)96-57(79(122)123)36-47-37-86-41-88-47/h14-25,37,41-43,51-63,103-106H,3-13,26-36,38-40,81-82H2,1-2H3,(H2,83,107)(H,86,88)(H,89,114)(H,90,111)(H,91,117)(H,92,110)(H,93,109)(H,94,115)(H,95,118)(H,96,112)(H,97,116)(H,98,108)(H,99,113)(H,122,123)(H4,84,85,87)/t42-,43-,51-,52-,53-,54-,55-,56-,57-,58-,59-,60-,61-,62-,63-/m0/s1
• InChIKey: UUTLJGUXRVWOSI-YYXAXUJHSA-N
• SMILES: CC1C(=O)N2CCCC2C(=O)NC(C(=O)NC(C(=O)NC(CSSCC(C(=O)NC(C(=O)N1)CO)NC(=O)C(C)N)C(=O)NC(CC3=CC=C(C=C3)O)C(=O)NC(CCC(=O)N)C(=O)NC(CCCCN)C(=O)N4CCCC4C(=O)N5CCCC5C(=O)NC(CC6=CC=C(C=C6)O)C(=O)NC(CC7=CNC=N7)C(=O)O)CC8=CC=C(C=C8)O)CCCNC(=N)N

Balixafortide, also known as POL6326, is an orally bioavailable inhibitor of CXC chemokine receptor 4 (CXCR4) with receptor binding and hematopoietic stem cell-mobilization activities. CXCR4 inhibitor POL6326 binds to the chemokine receptor CXCR4, thereby preventing the binding of stromal derived factor-1 (SDF-1 or CXCL12) to the CXCR4 receptor and subsequent receptor activation. This may induce the mobilization of hematopoietic stem and progenitor cells from the bone marrow into blood. CXCR4, a chemokine receptor belonging to the G protein-coupled receptor (GPCR) gene family, plays an important role in chemotaxis and angiogenesis and is upregulated in several tumor cell types.

Reference

1:J Transl Med. 2017 Jan 3;15(1):2. doi: 10.1186/s12967-016-1107-2. Mobilization of hematopoietic stem cells with the novel CXCR4 antagonist POL6326 (balixafortide) in healthy volunteers-results of a dose escalation trial.Karpova D,Bräuninger S,Wiercinska E,Krämer A,Stock B,Graff J,Martin H,Wach A,Escot C,Douglas G,Romagnoli B,Chevalier E,Dembowski K,Hooftman L,Bonig H, PMID: 28049490 PMCID: PMC5209880 DOI: 10.1186/s12967-016-1107-2 Abstract: BACKGROUND: Certain disadvantages of the standard hematopoietic stem and progenitor cell (HSPC) mobilizing agent G-CSF fuel the quest for alternatives. We herein report results of a Phase I dose escalation trial comparing mobilization with a peptidic CXCR4 antagonist POL6326 (balixafortide) vs. G-CSF.METHODS: Healthy male volunteer donors with a documented average mobilization response to G-CSF received, following ≥6 weeks wash-out, a 1-2 h infusion of 500-2500 µg/kg of balixafortide. Safety, tolerability, pharmacokinetics and pharmacodynamics were assessed.RESULTS: Balixafortide was well tolerated and rated favorably over G-CSF by subjects. At all doses tested balixafortide mobilized HSPC. In the dose range between 1500 and 2500 µg/kg mobilization was similar, reaching 38.2 ± 2.8 CD34 + cells/µL (mean ± SEM). Balixafortide caused mixed leukocytosis in the mid-20 K/µL range. B-lymphocytosis was more pronounced, whereas neutrophilia and monocytosis were markedly less accentuated with balixafortide compared to G-CSF. At the 24 h time point, leukocytes had largely normalized.CONCLUSIONS: Balixafortide is safe, well tolerated, and induces efficient mobilization of HSPCs in healthy male volunteers. Based on experience with current apheresis technology, the observed mobilization at doses ≥1500 µg/kg of balixafortide is predicted to yield in a single apheresis a standard dose of 4× 10E6 CD34+ cells/kg from most individuals donating for an approximately weight-matched recipient. Exploration of alternative dosing regimens may provide even higher mobilization responses. Trial Registration European Medicines Agency (EudraCT-Nr. 2011-003316-23) and clinicaltrials.gov (NCT01841476).