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| 5mg |
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| 25mg |
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Purity: ≥98%
BIIB021 (CNF2024; BIIB-021; CNF-2024; CNF 2024; BIIB 021) is an orally bioavailable and purine-based small-molecule inhibitor of HSP90 (heat shock protein 90) with potential anticancer activity. It inhibits HSP90 with a Ki and an EC50 of 1.7 nM and 38 nM, respectively. BIIB021 exhibits excellent in vivo antitumor efficacy in many tumor xenograft models such as N87, BT474, CWR22, U87, SKOV3 and Panc-1.
| ln Vitro |
BIIB021 binds to Hsp90's ATP-binding pocket and obstructs its chaperone activity, causing client protein degradation and inhibiting tumor growth. With an IC50 of 0.06-0.31 μM, BIIB021 inhibits the proliferation of tumor cells (BT474, MCF-7, N87, HT29, H1650, H1299, H69, and H82). Heat shock proteins Hsp70 and Hsp27 are expressed more frequently when BIIB021 is present, and it also causes the degradation of Hsp90 client proteins, such as HER-2, Akt, and Raf-1 [1]. With an IC50 of 0.24-0.8 μM, BIIB021 inhibits Hodgkin lymphoma cells (KM-H2, L428, L540, L540cy, L591, L1236, and DEV). In healthy persons' lymphocytes, BIIB021 exhibited minimal activity. Despite IκB deficiency, BIIB021 reduces the constitutive activity of NF-κB. Hodgkin lymphoma cells exposed to BIIB021 express more ligands for the activating NK cell receptor NKG2D, making them more susceptible to NK cell-mediated death [2]. By increasing the in vitro radiosensitivity of HNSCCA cell lines (UM11B and JHU12), BIIB021 also decreases the expression of important radioresponsive proteins, promotes G2 arrest, and increases cell death [3]. When it comes to adrenocortical cancer H295R, BIIB021 is far more active than 17-AAG. NQO1 deletion or Bcl-2 overexpression had no effect on BIIB021's cytotoxic action, and molecular damage was linked to decreased 17-AAG cell death but did not stop client loss. Additionally, 17-AAG-resistant cell lines (NIH-H69, MES SA Dx5, NCI-ADR-RES, Nalm6) exhibit the activity of BIIB021 [4].
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| ln Vivo |
In numerous tumor xenograft models, such as N87, BT474, CWR22, U87, SKOV3, and Panc-1, oral administration of BIIB021 inhibits tumor growth[1]. A dosage of 120 mg/kg of BIIB021 efficiently suppresses the growth of L540cy tumor[2]. Radiation's antitumor growth effect in JHU12 xenograft is markedly enhanced by BIIB021[3].
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| References |
[1]. Lundgren, Karen., et al. BIIB021, an orally available, fully synthetic small-molecule inhibitor of the heat shock protein Hsp90. Molecular Cancer Therapeutics (2009), 8(4), 921-929.
[2]. B?ll B, et al. Heat shock protein 90 inhibitor BIIB021 (CNF2024) depletes NF-kappaB and sensitizes Hodgkin's lymphoma cells for natural killer cell-mediated cytotoxicity. Clin Cancer Res. 2009 Aug 15;15(16):5108-16. [3]. Yin X, et al. BIIB021, a novel Hsp90 inhibitor, sensitizes head and neck squamous cell carcinoma to radiotherapy. Int J Cancer. 2010 Mar 1;126(5):1216-25 [4]. Zhang H, et al. BIIB021, a synthetic Hsp90 inhibitor, has broad application against tumors with acquired multidrug resistance. Int J Cancer. 2010 Mar 1;126(5):1226-34 |
| Molecular Formula |
C
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|---|---|
| Molecular Weight |
318.76
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| CAS # |
848695-25-0
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| Related CAS # |
1225041-97-3 (mesylate);848695-25-0;
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| SMILES |
NC1=NC(Cl)=C2N=CN(CC3=NC=C(C)C(OC)=C3C)C2=N1
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| InChi Key |
QULDDKSCVCJTPV-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C14H15ClN6O/c1-7-4-17-9(8(2)11(7)22-3)5-21-6-18-10-12(15)19-14(16)20-13(10)21/h4,6H,5H2,1-3H3,(H2,16,19,20)
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| Chemical Name |
[6-Chloro-9-(4-methoxy-3,5-dimethylpyridin-2-ylmethyl)-9H-purin-2-yl]amine
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| Synonyms |
CNF2024; BIIB-021; CNF-2024; CNF 2024; BIIB021; BIIB 021;
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| 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)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.84 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 25.0 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: ≥ 2.5 mg/mL (7.84 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. View More
Solubility in Formulation 3: 30% propylene glycol, 5% Tween 80, 65% D5W: 30 mg/mL |
| Preparing Stock Solutions | 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 | |
| 10 mM | 0.3137 mL | 1.5686 mL | 3.1372 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.
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.
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