BNC-105
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MedKoo CAT#: 204760

CAS#: 945771-74-4

Description: BNC105 is a novel compound being developed by Bionomics as a Vascular Disrupting Agent (VDA) for treatment of cancer. VDAs are drugs that disrupt the blood vessels that nourish tumours. BNC105 acts as a tubulin polymerization inhibitor and displays 80-fold higher potency against endothelial cells than that of CA4P. CA4P is a VDA currently under evaluation in phase III clinical trials. BNC105 is more potent and offers a wider therapeutic window. CA4P produces 90% vascular disruption at its no observed adverse event level (NOAEL), whereas BNC105 causes 95% vascular disruption at 1/8th of its NOAEL. Tissue distribution analysis of BNC105 in tumor-bearing mice showed that while the drug is cleared from all tissues 24 hours after administration, it is still present at high concentrations within the solid tumor mass. Furthermore, BNC105 treatment causes tumor regressions with complete tumor clearance in 20% of treated animals.

Chemical Structure

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BNC-105
CAS# 945771-74-4
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 204760
Name: BNC-105
CAS#: 945771-74-4
Chemical Formula: C20H20O7
Exact Mass: 372.12
Molecular Weight: 372.370
Elemental Analysis: C, 64.51; H, 5.41; O, 30.08

Price and Availability

Size Price Availability Quantity
10mg USD 190 Ready to ship
25mg USD 350 Ready to ship
50mg USD 550 Ready to ship
100mg USD 950 Ready to ship
200mg USD 1450 Ready to ship
500mg USD 2450 Ready to ship
1g USD 3850 2 Weeks
2g USD 6450 2 Weeks
Bulk inquiry

Synonym: BCN105; BCN-105; BCN 105.

IUPAC/Chemical Name: (7-hydroxy-6-methoxy-2-methylbenzofuran-3-yl)(3,4,5-trimethoxyphenyl)methanone

InChi Key: RADMJHVVIZTENA-UHFFFAOYSA-N

InChi Code: InChI=1S/C20H20O7/c1-10-16(12-6-7-13(23-2)18(22)19(12)27-10)17(21)11-8-14(24-3)20(26-5)15(9-11)25-4/h6-9,22H,1-5H3

SMILES Code: O=C(C1=C(C)OC2=C(O)C(OC)=CC=C12)C3=CC(OC)=C(OC)C(OC)=C3

Appearance: Beige fluffy 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, not in water

Shelf Life: >2 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: BNC105 is a novel compound being developed by Bionomics as a Vascular Disrupting Agent (VDA) for treatment of cancer. VDAs are drugs that disrupt the blood vessels that nourish tumours.   BNC105 acts as a tubulin polymerization inhibitor and displays 80-fold higher potency against endothelial cells that are actively proliferating or are engaged in the formation of in vitro capillaries compared with nonproliferating endothelial cells or endothelium found in stable capillaries. This selectivity was not observed with CA4, a VDA currently under evaluation in phase III clinical trials. BNC105 is more potent and offers a wider therapeutic window. CA4 produces 90% vascular disruption at its no observed adverse event level (NOAEL), whereas BNC105 causes 95% vascular disruption at 1/8th of its NOAEL. Tissue distribution analysis of BNC105 in tumor-bearing mice showed that while the drug is cleared from all tissues 24 hours after administration, it is still present at high concentrations within the solid tumor mass. Furthermore, BNC105 treatment causes tumor regressions with complete tumor clearance in 20% of treated animals. (source: Mol Cancer Ther. 2010 Jun;9(6):1562-73. Epub 2010 Jun 1.)   According to Bonomics's website, BNC105 has several important properties that make it superior to VDAs being developed by other companies: including (1) BNC105 has a higher therapeutic index, meaning that that there is a larger window between its effective dose and the dose at which toxic effects are observed (in mice the therapeutic index for BNC105 is 26 times greater than that for Combretastatin A4 (CA4), another VDA in development). (2) BNC105 has a "dual mode" of operation. In addition to its effect as a VDA, BNC105 has a direct cytotoxic effect upon tumour cells.  (3) BNC105 to inhibit tumour growth as a single agent, an effect not seen with combretastatin.  It also effectively combines with radiation therapy and with other cytotoxic agents to generate a greater anti-tumour response. (4)  BNC105 is selectively retained within tumours.(5) BNC105 does not appear to be affected by the multidrug resistance gene, P-glycoprotein which affects the bioavailability of many anticancer agents by causing secretion of the drug out of cells. (source: http://www.bionomics.com.au/page.php?section=103).   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.         

Biological target: BNC105 is a tubulin polymerization inhibitor with potent antiproliferative and tumor vascular disrupting properties.
In vitro activity: BNC105 exhibits an EC50 for chromatin condensation of <20 nmol/L, while vinblastine and CA4 demonstrated EC50 ≥ 100 nmol/L. The ability of these drugs to impact the biomarkers phospho-JNK and Noxa correlated with apoptosis. BNC105 was ∼10x more potent than vinblastine and CA4 to activate JNK and Noxa and induce apoptosis (Fig. 1A). Reference: Cancer Biol Ther. 2016 Mar; 17(3): 291–299. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4847999/
In vivo activity: BNC105 is more potent and offers a wider therapeutic window. CA4 produces 90% vascular disruption at its no observed adverse event level (NOAEL), whereas BNC105 causes 95% vascular disruption at 1/8th of its NOAEL. Tissue distribution analysis of BNC105 in tumor-bearing mice showed that while the drug is cleared from all tissues 24 hours after administration, it is still present at high concentrations within the solid tumor mass. Furthermore, BNC105 treatment causes tumor regressions with complete tumor clearance in 20% of treated animals. Reference: J Med Chem. 2011 Sep 8; 54(17): 6014–6027. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3172808/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 25.0 67.14

Preparing Stock Solutions

The following data is based on the product molecular weight 372.37 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.

Recalculate based on batch purity %
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
Formulation protocol: 1. Bates D, Feris EJ, Danilov AV, Eastman A. Rapid induction of apoptosis in chronic lymphocytic leukemia cells by the microtubule disrupting agent BNC105. Cancer Biol Ther. 2016;17(3):291-9. doi: 10.1080/15384047.2016.1139245. Epub 2016 Jan 30. PMID: 26891146; PMCID: PMC4847999. 2. 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. PMID: 21774499; PMCID: PMC3172808. 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. PMID: 20515948.
In vitro protocol: 1. Bates D, Feris EJ, Danilov AV, Eastman A. Rapid induction of apoptosis in chronic lymphocytic leukemia cells by the microtubule disrupting agent BNC105. Cancer Biol Ther. 2016;17(3):291-9. doi: 10.1080/15384047.2016.1139245. Epub 2016 Jan 30. PMID: 26891146; PMCID: PMC4847999.
In vivo protocol: 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. PMID: 21774499; PMCID: PMC3172808. 2. 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. PMID: 20515948.

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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. 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. 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. Epub 2010 Jun 1. PubMed PMID: 20515948.