Home Cytoskeletal Signaling HSP (HSP90) inhibitor BIIB021 For research use only.

BIIB021

Synonyms: CNF2024

BIIB021 (CNF2024) is an orally available, fully synthetic small-molecule inhibitor of HSP90 with Ki and EC50 of 1.7 nM and 38 nM, respectively. Phase 2.

BIIB021 Chemical Structure

BIIB021 Chemical Structure

CAS No. 848695-25-0

Purity & Quality Control

BIIB021 Related Products

Signaling Pathway

HSP (HSP90) Signaling Pathways

HSP (HSP90) Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
MCF7 Function assay Inhibition of HSP90-mediated client protein HER2 degradation in human MCF7 cells, IC50=0.038μM 20055425
BT474 Function assay Binding affinity to Hsp90 nucleotide binding domain in human BT474 cells, IC50=0.14μM 20608738
MCF7 Function assay Inhibition of HSP90alpha in human MCF7 cells assessed as degradation of Her-2, EC50=0.038μM 22938030
NCI-H295 Cytotoxicity assay 120 mg/kg 5 days Cytotoxicity against human NCI-H295 cells overexpressing PGP xenografted in athymic mouse assessed as inhibition of tumor growth at 120 mg/kg, po qd for 5 days per week for 4 weeks 22938030
Sf9 Function assay 3 hrs Binding affinity to human N-terminal polyHis-tagged HSP90alpha (D9 to E236) alpha-helix conformation expressed in insect sf9 cells after 3 hrs by fluorescence polarization assay, Ki=0.002μM 24332488
Sf9 Function assay 3 hrs Binding affinity to human N-terminal polyHis-tagged HSP90beta (D9 to E236) expressed in insect sf9 cells after 3 hrs by fluorescence polarization assay, Ki=0.004μM 24332488
NCI-H1299 Function assay 12 hrs Reduction in oxygen consumption rate in human NCI-H1299 cells incubated for 12 hrs 25383915
HeLa Function assay 10 uM 6 hrs Inhibition of HSP90 in human HeLa cells assessed as induction of chk1 degradation at 10 uM after 6 hrs by Western blot method 28816449
HeLa Function assay 10 uM 6 hrs Inhibition of HSP90 in human HeLa cells assessed as induction of Akt degradation at 10 uM after 6 hrs by Western blot method 28816449
HeLa Function assay 10 uM 6 hrs Inhibition of HSP90 in human HeLa cells assessed as induction of HSP70 protein expression at 10 uM after 6 hrs by Western blot method 28816449
PC3 Function assay 10 uM 6 hrs Inhibition of HSP90 in human PC3 cells assessed as induction of chk1 degradation at 10 uM after 6 hrs by Western blot method 28816449
PC3 Function assay 10 uM 6 hrs Inhibition of HSP90 in human PC3 cells assessed as induction of Akt degradation at 10 uM after 6 hrs by Western blot method 28816449
PC3 Function assay 10 uM 6 hrs Inhibition of HSP90 in human PC3 cells assessed as induction of HSP70 protein expression at 10 uM after 6 hrs by Western blot method 28816449
TC32 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells 29435139
SJ-GBM2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells 29435139
NB-EBc1 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells 29435139
SK-N-SH qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells 29435139
NB1643 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells 29435139
LAN-5 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells 29435139
Rh18 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells 29435139
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells 29435139
Rh41 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells 29435139
HCT116 Antiproliferative assay 48 hrs Antiproliferative activity against human HCT116 cells after 48 hrs by sulforhodamine B assay, GI50=0.15μM 29567459
A549 Antiproliferative assay 48 hrs Antiproliferative activity against human A549 cells after 48 hrs by sulforhodamine B assay, GI50=0.33μM 29567459
NCI-H1975 Antiproliferative assay 48 hrs Antiproliferative activity against human NCI-H1975 cells after 48 hrs by sulforhodamine B assay, GI50=0.38μM 29567459
HL60 Antiproliferative assay 48 hrs Antiproliferative activity against human HL60 cells after 48 hrs by sulforhodamine B assay, GI50=0.59μM 29567459
HL60 Function assay 1 uM 24 hrs Inhibition of HSP90 in human HL60 cells assessed as induction of HSP70 expression at 1 uM after 24 hrs by Western blot analysis 29567459
HL60 Function assay 1 uM 24 hrs Inhibition of HSP90 in human HL60 cells assessed as downregulation of phosphorylated Akt expression at 1 uM after 24 hrs by Western blot analysis 29567459
HL60 Function assay 1 uM 24 hrs Inhibition of HSP90 in human HL60 cells assessed as downregulation of phosphorylated STAT3 expression at 1 uM after 24 hrs by Western blot analysis 29567459
HL60 Function assay 1 uM 24 hrs Inhibition of HDAC in human HL60 cells assessed as upregulation of acetyl-alpha-tubulin levels at 1 uM after 24 hrs by Western blot analysis 29567459
HL60 Function assay 1 uM 24 hrs Inhibition of HDAC in human HL60 cells assessed as upregulation of acetylated histone H3 levels at 1 uM after 24 hrs by Western blot analysis 29567459
MCF7 Antiproliferative assay Antiproliferative activity against human MCF7 cells, IC50=0.31μM 31663736
Click to View More Cell Line Experimental Data

Biological Activity

Description BIIB021 (CNF2024) is an orally available, fully synthetic small-molecule inhibitor of HSP90 with Ki and EC50 of 1.7 nM and 38 nM, respectively. Phase 2.
Targets
HSP90 [1]
(Cell-free assay)
1.7 nM(Ki)
In vitro
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 enhanced the in vitro radiosensitivity of HNSCCA cell lines (UM11B and JHU12) with a corresponding reduction in the expression of key radioresponsive proteins, increased apoptotic cells and enhance G2 arrest. [3] BIIB021 is considerably more active than 17-AAG against adrenocortical carcinoma H295R, both in vitro and in vivo. 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 and etc.). [4]
Kinase Assay Hsp90 Binding Assay
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 contained no BIIB021 or no Hsp90, respectively. The data are fit to a four-parameter curve and IC50 is generated.
Cell Research Cell lines BT474, MCF-7, N87, HT29, H1650, H1299, H69 and H82 cells
Concentrations 3 nM - 1 μM
Incubation Time 5 days
Method 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 viabilit
In Vivo
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]
Animal Research Animal Models N87, BT474, CWR22, U87, SKOV3 and Panc-1 tumor models in BALB/c and athymic mice
Dosages 31, 62.5, and 125 mg/kg
Administration Orally administered once daily
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT01017198 Completed
Advanced Solid Tumors
Biogen
 November 2009 Phase 1
NCT01004081 Completed
Breast Cancer
Biogen
 November 2009 Phase 2
NCT00618735 Completed
Advanced Solid Tumors
Biogen
 February 2008 Phase 1
NCT00618319 Completed
GIST
Biogen
 February 2008 Phase 2

Chemical Information & Solubility

Molecular Weight 318.76 Formula

C14H15ClN6O
CAS No. 848695-25-0 SDF Download BIIB021 SDF
Smiles CC1=CN=C(C(=C1OC)C)CN2C=NC3=C2N=C(N=C3Cl)N
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 64 mg/mL ( (200.77 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 12 mg/mL

Water : Insoluble


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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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