2. Cell Cycle/DNA Damage Metabolic Enzyme/Protease Autophagy
  3. HSP Autophagy
  4. BIIB021

BIIB021 (CNF2024) est un inhibiteur de HSP90 qui est entièrement synthétique et oralement actif, avec un Ki et un EC50 de 1,7 nM et 38 nM, respectivement.

BIIB021 (CNF2024) is an orally active, fully synthetic inhibitor of HSP90 with a Ki and an EC50 of 1.7 nM and 38 nM, respectively.

For research use only. We do not sell to patients.

BIIB021 Chemical Structure

BIIB021 Chemical Structure

CAS No. : 848695-25-0

Size Price Stock Quantity
Free Sample (0.1 - 0.5 mg)   Apply Now  
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO
ready for reconstitution
 USD 66 In-stock
Solution
10 mM * 1 mL in DMSO USD 66 In-stock
Solid
5 mg USD 49 In-stock
10 mg USD 79 In-stock
25 mg USD 142 In-stock
50 mg USD 214 In-stock
100 mg USD 300 In-stock
200 mg   Get quote  
500 mg   Get quote  

* Please select Quantity before adding items.

This product is a controlled substance and not for sale in your territory.

Customer Review

Based on 3 publication(s) in Google Scholar

BIIB021 Related Antibodies

Top Publications Citing Use of Products

View All HSP Isoform Specific Products:

View All Isoforms
HSP40 HSP70 HSP90 HSP105 HSF1 HSP HSPA5

  • Biological Activity

  • Protocol

  • Purity & Documentation

  • References

  • Customer Review

Description

BIIB021 (CNF2024) is an orally active, fully synthetic inhibitor of HSP90 with a Ki and an EC50 of 1.7 nM and 38 nM, respectively[1].

IC50 & Target

HSP90

1.7 nM (Ki)

HSP90

38 nM (EC50)

In Vitro

BIIB021 binds in the ATP-binding pocket of Hsp90, interferes with Hsp90 chaperone function, and results in client protein degradation and tumor growth inhibition. BIIB021 inhibits tumor cell (BT474, MCF-7, N87, HT29, H1650, H1299, H69 and H82) proliferation with IC50 from 0.06-0.31 μM. BIIB021 induces the degradation of Hsp90 client proteins including HER-2, Akt, and Raf-1 and up-regulated expression of the heat shock proteins Hsp70 and Hsp27[1].
BIIB021 inhibits Hodgkin's lymphoma cells (KM-H2, L428, L540, L540cy, L591, L1236 and DEV) with IC50 from 0.24-0.8 μM. BIIB021 shows low activity in lymphocytes from healthy individuals. BIIB021 inhibits the constitutive activity of NF-κB despite defective IκB. BIIB021 induces the expression of ligands for the activating NK cell receptor NKG2D on Hodgkin's lymphoma cells resulting in an increased susceptibility to NK cell-mediated killing[2].
BIIB021 enhances the in vitro radiosensitivity of HNSCCA cell lines (UM11B and JHU12) with a corresponding reduction in the expression of key radioresponsive proteins, increases apoptotic cells and enhances G2 arrest[3].
BIIB021 is considerably more active than 17-AAG against adrenocortical carcinoma H295R. The cytotoxic activity of BIIB021 is not influenced by loss of NQO1 or Bcl-2 overexpression, molecular lesions that do not prevent client loss but are nonetheless associated with reduced cell killing by 17-AAG. BIIB021 is also active in 17-AAG resistant cell lines (NIH-H69, MES SA Dx5, NCI-ADR-RES, Nalm6)[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

BIIB021 Related Antibodies
In Vivo

Oral administration of BIIB021 leads to tumor growth inhibition in many tumor xenograft models including N87, BT474, CWR22, U87, SKOV3 and Panc-1[1].
BIIB021 effectively inhibits growth of L540cy tumor at a dose of 120 mg/kg[2]. BIIB021 significantly enhances antitumor growth effect of radiation in JHU12 xenograft[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
Molecular Weight

318.76

Formula

C14H15ClN6O
CAS No.
Appearance

Solid

Color

White to off-white

SMILES

ClC1=C2C(N(C=N2)CC3=C(C(OC)=C(C=N3)C)C)=NC(N)=N1
Shipping

Room temperature in continental US; may vary elsewhere.
Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 2 years
-20°C 1 year
Solvent & Solubility
In Vitro: 

DMSO : ≥ 45 mg/mL (141.17 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

*"≥" means soluble, but saturation unknown.

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 3.1372 mL 15.6858 mL 31.3716 mL
5 mM 0.6274 mL 3.1372 mL 6.2743 mL
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

  • Molarity Calculator

  • Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass
=
Concentration
×
Volume
×
Molecular Weight *

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start)

C1

×
Volume (start)

V1

=
Concentration (final)

C2

×
Volume (final)

V2

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

  • Protocol 1

    Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% Saline

    Solubility: ≥ 2.5 mg/mL (7.84 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

    Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
  • Protocol 2

    Add each solvent one by one:  10% DMSO    90% Corn Oil

    Solubility: ≥ 2.5 mg/mL (7.84 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

g

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO +
% 
+
%
Tween-80 +
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration: mg/mL
Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
 If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Purity & Documentation

Purity: 99.19%

COA (251 KB) LCMS (266 KB)

Handling Instructions (2659 KB)
References
Kinase Assay
[1]

For fluorescence polarization competition measurements, the FITC-geldanamycin probe (20 nM) is reduced with 2 mM TCEP at room temperature for 3 hours, after which the solution is aliquoted and stored at -80°C until used. Recombinant human Hsp90α (0.8 nM) and reduced FITC-geldanamycin (2 nM) are incubated in a 96-well microplate at room temperature for 3 hours in the presence of assay buffer containing 20 mM HEPES (pH 7.4), 50 mM KCl, 5 mM MgCl2, 20 mM Na2MoO4, 2 mM DTT, 0.1 mg/mL BGG, and 0.1% (v/v) CHAPS. Following this preincubation, BIIB021 in 100% DMSO is then added to final concentrations of 0.2 nM to 10 μM (final volume 100 μL, 2% DMSO). The reaction is incubated for 16 hours at room temperature and fluorescence is then measured in an Analyst plate reader, excitation=485 nm, emission=535 nm. High and low controls contain no BIIB021 or no Hsp90, respectively. The data are fit to a four-parameter curve and IC50 is generated.

MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Assay
[1]

A modified tetrazolium salt assay is used to measure the IC50. Tumor cells are added to 96-well plates and propagated for 24 hours before BIIB021 addition. BIIB021 is added to the plated cells. DMSO (0.03-0.003%) is included as a vehicle control. After incubation phenazine methosulfate (stock concentration 1 mg/mL) and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (stock concentration 2 mg/mL) are mixed at a ratio of 1:20 and added to each well of a 96-well plate. Reduction of 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt gives rise to a soluble formazan product that is secreted into the culture medium. After 4 hours incubation, the formazan product is quantitated spectrophotometrically at a wavelength of 490 nm. Data are acquired using SOFTmaxPRO software, and 100% viability is defined as the A490 of DMSO-treated cells stained with 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (the mean A490 of cells treated with DMSO at a range of 0.03-0.003%). Percent viability of each sample is calculated from the A490 values as follows: % viability=(A490 nm sample/A490 nm DMSO-treated cells × 100). The IC50 is defined as the concentration that gives rise to 50% inhibition of cell viability.

MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration
[1]

BALB/c and athymic mice are obtained from Harlan Sprague-Dawley at age 6 to 8 weeks. The mice are maintained in sterilized cages in a ventilated caging system with a 12 h light/12 h dark photoperiod at temperature of 21°C to 23°C and a relative humidity of 50±5%. Irradiated pelleted food and autoclaved deionized water are provided ad libitum. Animals are identified by the use of individually numbered ear tags. N87 tumor fragments (appr 2 mm3) are implanted s.c. in the right flank of the animal. BIIB021 is administered to animals bearing N87 stomach carcinoma tumors at doses of 31, 62.5, and 125 mg/kg, once daily, from Monday to Friday, for 5 weeks. Tumor dimensions are measured using calipers and tumor volumes are calculated using the equation for an ellipsoid sphere (l×w2)/2=mm3, where l and w refer to the larger and smaller dimensions collected at each measurement, respectively. Tumor volumes are measured and animals are weighed and monitored for toxicity at least twice weekly. P values are calculated using the two-tailed Student's t test to assess the difference in tumor volumes between control and treated groups. P<0.05 is considered significant.

MCE has not independently confirmed the accuracy of these methods. They are for reference only.
References

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 3.1372 mL 15.6858 mL 31.3716 mL 78.4289 mL
5 mM 0.6274 mL 3.1372 mL 6.2743 mL 15.6858 mL
10 mM 0.3137 mL 1.5686 mL 3.1372 mL 7.8429 mL
15 mM 0.2091 mL 1.0457 mL 2.0914 mL 5.2286 mL
20 mM 0.1569 mL 0.7843 mL 1.5686 mL 3.9214 mL
25 mM 0.1255 mL 0.6274 mL 1.2549 mL 3.1372 mL
30 mM 0.1046 mL 0.5229 mL 1.0457 mL 2.6143 mL
40 mM 0.0784 mL 0.3921 mL 0.7843 mL 1.9607 mL
50 mM 0.0627 mL 0.3137 mL 0.6274 mL 1.5686 mL
60 mM 0.0523 mL 0.2614 mL 0.5229 mL 1.3071 mL
80 mM 0.0392 mL 0.1961 mL 0.3921 mL 0.9804 mL
100 mM 0.0314 mL 0.1569 mL 0.3137 mL 0.7843 mL
  • No file chosen (Maximum size is: 1024 Kb)
  • If you have published this work, please enter the PubMed ID.
  • Your name will appear on the site.

BIIB021 Related Classifications

Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

BIIB021848695-25-0CNF2024BIIB 021BIIB-021CNF 2024CNF-2024HSPAutophagyHeat shock proteinsInhibitorinhibitorinhibit

Your Recently Viewed Products:

Inquiry Online

Your information is safe with us. * Required Fields.

Product Name

  

Salutation

Applicant Name *

 

Email Address *

Phone Number *

 

Organization Name *

Department *

 

Requested quantity *

Country or Region *

      

Remarks

Bulk Inquiry

Inquiry Information

Product Name:
BIIB021
Cat. No.:
HY-10212
Quantity:
MCE Japan Authorized Agent:

Customer Review

Thank You for Your Feedback!

Request for HNMR Report

Please fill out this form to request the QC report. We will send it to your Email address shortly.

Your information is safe with us. * Required Fields.

Product Name

  

Lot #

Applicant Name *

 

Email Address *

Phone Number

 

Department *

Organization Name *

 

Country or Region *

Remarks

Request for HNMR Report

We have received your request and will respond to you as soon as possible.