BNC105P

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

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.

Price and Availability

BNC105P, purity > 98%, is not in stock, may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.

Chemical Structure

Theoretical Analysis

MedKoo Cat#: 205749Name: BNC105PCAS#: 945771-96-0 (sodium)Chemical Formula: C20H21O10PExact Mass: 452.08723Molecular Weight: 452.3485Elemental 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+]

Technical Data

Additional Information

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.   

References

1: Flynn BL, Gill GS, Grobelny DW, Chaplin JH, PaulD, Leske AF, Lavranos TC, Chalmers DK,  Charman SA, Kostewicz E,Shackleford DM, Morizzi J, Hamel E, Jung MK, Kremmidiotis G. Discoveryof 7-hydroxy-6-methoxy-2-methyl-3-(3,4,5-trimethoxybenzoyl)benzo[b]furan(BNC105), a tubulin polymerization inhibitor with potentantiproliferative 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 pharmacokineticevaluation of BNC105P: a phase I trial of a novel vascular disruptingagent and inhibitor of cancer cell proliferation. Clin Cancer Res. 2011Aug 1;17(15):5152-60. doi: 10.1158/1078-0432.CCR-11-0937. Epub 2011 Jun20. 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 tubulinpolymerization inhibitor that selectively disrupts tumor vasculature anddisplays single-agent antitumor efficacy. Mol Cancer Ther. 2010Jun;9(6):1562-73. doi: 10.1158/1535-7163.MCT-09-0815. Epub 2010 Jun 1.PubMed PMID: 20515948.