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BHPI

Cat No.:V5504 Purity: ≥98%
BHPI is an inhibitor (blocker/antagonist) of the nuclear receptor ER_alpha_, which can inhibit cancer/tumor cell protein synthesis and activate the unfolded protein response (UPR).
BHPI
BHPI Chemical Structure CAS No.: 56632-39-4
Product category: New15
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
5mg
10mg
50mg
Other Sizes
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Product Description
BHPI is an inhibitor (blocker/antagonist) of the nuclear receptor ER_alpha_, which can inhibit cancer/tumor cell protein synthesis and activate the unfolded protein response (UPR).
Biological Activity I Assay Protocols (From Reference)
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C21H17NO3
Molecular Weight
331.36458
Exact Mass
331.121
CAS #
56632-39-4
PubChem CID
3860640
Appearance
White to off-white solid powder
LogP
3.777
Hydrogen Bond Donor Count
3
Hydrogen Bond Acceptor Count
3
Rotatable Bond Count
2
Heavy Atom Count
25
Complexity
469
Defined Atom Stereocenter Count
0
InChi Key
FABLAHMQSQFDHR-UHFFFAOYSA-N
InChi Code
InChI=1S/C21H17NO3/c1-13-3-2-4-18-19(13)22-20(25)21(18,14-5-9-16(23)10-6-14)15-7-11-17(24)12-8-15/h2-12,23-24H,1H3,(H,22,25)
Chemical Name
3,3-bis(4-hydroxyphenyl)-7-methyl-1H-indol-2-one
HS Tariff Code
2934.99.9001
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO : ~120 mg/mL (~362.14 mM)
Solubility (In Vivo)
Solubility in Formulation 1: ≥ 3 mg/mL (9.05 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 30.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

Solubility in Formulation 2: ≥ 3 mg/mL (9.05 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 30.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 3.0179 mL 15.0893 mL 30.1787 mL
5 mM 0.6036 mL 3.0179 mL 6.0357 mL
10 mM 0.3018 mL 1.5089 mL 3.0179 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

Calculator

Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

  • Calculate the Mass of a compound required to prepare a solution of known volume and concentration
  • Calculate the Volume of solution required to dissolve a compound of known mass to a desired concentration
  • Calculate the Concentration of a solution resulting from a known mass of compound in a specific volume
An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
  • Enter 350.26 in the Molecular Weight (MW) box
  • Enter 10 in the Concentration box and choose the correct unit (mM)
  • Enter 5 in the Volume box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
  • Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
  • Enter 25 into the Concentration (End) box and select the correct unit (mM)
  • Enter 25 into the Volume (End) box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box
g/mol

Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:
  • To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.
Definitions of molecular mass, molecular weight, molar mass and molar weight:
  • Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
  • Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.
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Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

  • Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
  • Click the “Calculate” button
  • The answer appears in the Volume (to add to vial) box
In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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Calculation results

Working concentration mg/mL;

Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.

(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
             (2) Be sure to add the solvent(s) in order.

Biological Data
  • BHPI selectively inhibits proliferation of ERα+ cancer cells sensitive or resistant to drug therapy. BHPI inhibits proliferation of ERα+ (A) MCF-7 breast, (B) PEO4 ovarian, and (C) ECC-1 endometrial cancer cells with no effects on (D) counterpart ERα− cancer cells. Effects of BHPI on proliferation of drug-resistant cells: tamoxifen- and ICI-resistant (E) ZR-75-1 cells and (F) BT-474 breast cancer cells. (G) T47D cells treated with 1 μM BHPI or competitor antiestrogens (4-OHT, RAL, ICI) in the presence or absence of E2 and/or EGF. Proliferation of (H) cisplatin-resistant Caov-3 ovarian cancer cells and (I) multidrug-resistant OVCAR-3 ovarian cancer cells treated with BHPI, or the antiestrogens 4-OHT or ICI. Concentrations are as follows: E2, 1 nM (E, G, and H) or 10 nM (A–C, F, and I); EGF, 50 ng/mL (G); ICI, 1 μM (E, G, and H), 5 μM (I); 4-OHT, 1 μM (E, G, and H); RAL, 1 μM (G) “•” denotes cell number at day 0. Hatched bars denote antiestrogens (4-OHT, RAL, or ICI). Cell proliferation is expressed as mean ± SEM (n = 6). Andruska ND, et al. Estrogen receptor α inhibitor activates the unfolded protein response, blocks protein synthesis, and induces tumor regression. Proc Natl Acad Sci U S A. 2015 Apr 14;112(15):4737-42.
  • BHPI induces tumor regression in a mouse xenograft. Change in tumor cross-sectional area in mouse MCF-7 xenografts after 10 d of daily i.p. injections of either 15 mg/kg BHPI (blue) or vehicle control (red). Tumors had an average starting cross-sectional area of ∼45 mm2. For each tumor, area at day 0 was set to 0% change. Andruska ND, et al. Estrogen receptor α inhibitor activates the unfolded protein response, blocks protein synthesis, and induces tumor regression. Proc Natl Acad Sci U S A. 2015 Apr 14;112(15):4737-42.
  • BHPI selectively inhibits protein synthesis in ERα-positive cancer cells by activating PLCγ, depleting endoplasmic reticulum Ca2+, and activating the UPR. (A) Protein synthesis in BHPI-treated ERα+ and ERα− cells (n = 4). CHX, cycloheximide. (B) ERα is sufficient to make a cell sensitive to BHPI inhibition of protein synthesis. Protein synthesis in parental ERα− MCF10A cells and ERα-expressing MCF10AER IN9 cells (n = 4). (C) RNAi knockdown of ERα abolishes BHPI inhibition of protein synthesis. Protein synthesis in MCF10AER IN9 cells treated with noncoding (NC) siRNA or ERα siRNA SmartPool followed by 100 nM BHPI (n = 4). (D) Protein synthesis and immunoblot analysis of ERα protein levels in MCF10AER IN9 cells pretreated with 1 μM ICI for 24 h to degrade ERα, followed by treatment with 100 nM BHPI (n = 4). (E) Residual protein synthesis (untreated cells are set to 100%) after treatment with 1 μM BHPI in doxycycline-treated MCF7ERαHA cells expressing increasing levels of ERα (n = 6). Western blot shows ERα levels in each sample.Andruska ND, et al. Estrogen receptor α inhibitor activates the unfolded protein response, blocks protein synthesis, and induces tumor regression. Proc Natl Acad Sci U S A. 2015 Apr 14;112(15):4737-42.
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