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MedKoo CAT#: 205749
CAS#: 945771-96-0 (sodium)
Description: BNC105P is a benzofuran-based vascular disrupting agent (VDA) prodrug with potential anti-vascular and antineoplastic activities. Upon administration vascular disrupting agent BNC105P, the disodium phosphate ester of BNC105, is rapidly converted to BNC105; in activated endothelial cells, BNC105 binds to tubulin and inhibits its polymerization, which may result in a blockage of mitotic spindle formation, cell cycle arrest, and disruption of the tumor vasculature. Hypoxic conditions ensue, depriving tumor cells of nutrients and resulting in tumor cell apoptosis. In addition to its VDA activity, this agent has a direct cytotoxic effect on tumor cells by inhibiting tubulin polymerization. BNC105 is not a substrate for the multidrug-resistance P-glycoprotein (Pgp) transporter.
MedKoo Cat#: 205749
CAS#: 945771-96-0 (sodium)
Chemical Formula: C20H21O10P
Exact Mass: 452.08723
Molecular Weight: 452.3485
Elemental Analysis: C, 53.10; H, 4.68; O, 35.37; P, 6.85
Related CAS #: 945771-96-0 (sodium) 945772-45-2 (free acid)
Synonym: BNC105P; BNC 105P; BNC-105P
IUPAC/Chemical Name: sodium 6-methoxy-2-methyl-3-(3,4,5-trimethoxybenzoyl)benzofuran-7-yl phosphate
InChi Key: VVIPLWCZZYERCA-UHFFFAOYSA-L
InChi Code: InChI=1S/C20H21O10P.2Na/c1-10-16(17(21)11-8-14(26-3)19(28-5)15(9-11)27-4)12-6-7-13(25-2)20(18(12)29-10)30-31(22,23)24;;/h6-9H,1-5H3,(H2,22,23,24);;/q;2*+1/p-2
SMILES Code: O=P([O-])([O-])OC1=C(OC(C)=C2C(C3=CC(OC)=C(OC)C(OC)=C3)=O)C2=CC=C1OC.[Na+].[Na+]
BNC105P is the disodium phosphate ester prodrug of BNC105, a tubulin polymerization inhibitor (TPI) that exhibits a high degree of selectivity for tumor endothelial cells. BNC105P disrupts the vasculature within solid tumors in mice and acts as a direct antiproliferative, suppressing tumor cell growth in culture. BNC105P shows evidence of good efficacy in mice-bearing xenografts of several human-tumor types, causing the regression of tumors, and in some cases tumor clearance. Evaluations in preclinical models of cancer have shown that BNC105P is more potent and displays a significantly improved therapeutic index compared with other VDAs in development . BNC105P achieves >95% vascular disruption as early as 3 hours post administration in tumor bearing mice when dosed at 10 mg/kg. This dose is well tolerated as a Day 1, Day 8 dose in a 21-day treatment cycle. (source: Clin Cancer Res. 2011 Aug 1;17(15):5152-60.).
BNC105P and BNC-105 are analogues of CA4 and CA4P their structures are showed as the following:
Source: Clin Cancer Res. 2011 Aug 1;17(15):5152-60.
1: Flynn BL, Gill GS, Grobelny DW, Chaplin JH, Paul D, Leske AF, Lavranos TC, Chalmers DK, Charman SA, Kostewicz E, Shackleford DM, Morizzi J, Hamel E, Jung MK, Kremmidiotis G. Discovery of 7-hydroxy-6-methoxy-2-methyl-3-(3,4,5-trimethoxybenzoyl)benzo[b]furan (BNC105), a tubulin polymerization inhibitor with potent antiproliferative and tumor vascular disrupting properties. J Med Chem. 2011 Sep 8;54(17):6014-27. doi: 10.1021/jm200454y. Epub 2011 Aug 5. PubMed PMID: 21774499; PubMed Central PMCID: PMC3172808.
2: Rischin D, Bibby DC, Chong G, Kremmidiotis G, Leske AF, Matthews CA, Wong SS, Rosen MA, Desai J. Clinical, pharmacodynamic, and pharmacokinetic evaluation of BNC105P: a phase I trial of a novel vascular disrupting agent and inhibitor of cancer cell proliferation. Clin Cancer Res. 2011 Aug 1;17(15):5152-60. doi: 10.1158/1078-0432.CCR-11-0937. Epub 2011 Jun 20. PubMed PMID: 21690571.
3: Kremmidiotis G, Leske AF, Lavranos TC, Beaumont D, Gasic J, Hall A, O'Callaghan M, Matthews CA, Flynn B. BNC105: a novel tubulin polymerization inhibitor that selectively disrupts tumor vasculature and displays single-agent antitumor efficacy. Mol Cancer Ther. 2010 Jun;9(6):1562-73. doi: 10.1158/1535-7163.MCT-09-0815. Epub 2010 Jun 1. PubMed PMID: 20515948.