Name: BIIB021
Brand: Selleck Chemicals
SKU: S1175
Rating: 5 (30 reviews)

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Controllo Qualità (Quality Control)

Lotto: Purezza: 99.89%

99.89

Target correlati	Akt Wnt/beta-catenin PKC ROCK Microtubule Associated Integrin Bcr-Abl Actin FAK Kinesin
Altro HSP Inibitori	Tanespimycin (17-AAG) Elesclomol (STA-4783) Luminespib (NVP-AUY922) Ganetespib (STA-9090) Alvespimycin (17-DMAG) Hydrochloride VER-155008 Onalespib (AT13387) Celastrol (Tripterine) Zelavespib (PU-H71) NVP-BEP800

Coltura cellulare, trattamento e concentrazione di lavoro
(Cell Culture, Treatment & Working Concentration)

Linee cellulari	Tipo di saggio	Concentrazione	Tempo di incubazione	Descrizione dell'attività	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
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Informazioni chimiche, conservazione e stabilità (Chemical Information, Storage & Stability)

Peso molecolare	318.76	Formula	C₁₄H₁₅ClN₆O	Conservazione (Dalla data di ricezione)	3 anni-20°Cpolvere
N. CAS	848695-25-0	Scarica SDF		Conservazione delle soluzioni stock	1 anno-80°Cin solvente 1 mese-20°Cin solvente
Sinonimi	CNF2024			Smiles	CC1=CN=C(C(=C1OC)C)CN2C=NC3=C2N=C(N=C3Cl)N

Solubilità (Solubility)

In vitro
Lotto:

DMSO : 64 mg/mL (200.77 mM)
(Il DMSO contaminato da umidità può ridurre la solubilità. Utilizzare DMSO fresco e anidro.)

Ethanol : 12 mg/mL

Water : Insoluble

Calcolatore di Molarità

Massa	Concentrazione	Volume	Peso molecolare
=	×	×

Calcolatore di Diluizione Calcolatore del Peso Molecolare

In vivo Lotto:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	30%propylene glycol 1 5%Tween80 2 65%D5W Validato dai laboratori Selleck. Se necessiti di modifiche a questa formulazione, contatta il nostro team di vendita per test personalizzati.	30.000mg/ml (94.11mM)	Taking the 1 mL working solution as an example, add 300 μL of 100 mg/ml clarified propylene glycol stock solution to 50 μL of Tween 80, mix evenly to clarify it; then continue to add 650 μL of D5W to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

Calcolatore di formulazione in vivo (Soluzione chiara)

Passo 1: Inserire le informazioni di seguito (Consigliato: Un animale aggiuntivo per tenere conto della perdita durante l'esperimento)

Dosaggio: mg/kg Peso medio degli animali: g Volume di dosaggio per animale:μL Numero di animali:

Passo 2: Inserire la formulazione in vivo (Questo è solo il calcolatore, non la formulazione. Contattateci prima se non c'è una formulazione in vivo nella sezione Solubilità.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Risultati del calcolo:

Concentrazione di lavoro: mg/ml;

Metodo per preparare il liquido master di DMSO: mg farmaco predissolto in μL DMSO ( Concentrazione del liquido master mg/mL, Vi preghiamo di contattarci prima se la concentrazione supera la solubilità del DMSO del lotto del farmaco. )

Metodo per preparare la formulazione in vivo: Prendere μL DMSO liquido master, quindi aggiungereμL PEG300, mescolare e chiarire, quindi aggiungereμL Tween 80, mescolare e chiarire, quindi aggiungere μL ddH₂O, mescolare e chiarire.

Metodo per preparare la formulazione in vivo: Prendere μL DMSO liquido master, quindi aggiungere μL Olio di mais, mescolare e chiarire.

Nota: 1. Si prega di assicurarsi che il liquido sia limpido prima di aggiungere il solvente successivo.
2. Assicurarsi di aggiungere il/i solvente/i in ordine. È necessario assicurarsi che la soluzione ottenuta, nell'aggiunta precedente, sia una soluzione limpida prima di procedere all'aggiunta del solvente successivo. Metodi fisici come il vortex, gli ultrasuoni o il bagno d'acqua calda possono essere utilizzati per facilitare la dissoluzione.

Meccanismo d'azione (Mechanism of Action)

Targets/IC₅₀/Ki	HSP90 (Cell-free assay) 1.7 nM(Ki)
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. This compound inhibits tumor cell (BT474, MCF-7, N87, HT29, H1650, H1299, H69 and H82) proliferation with IC50 from 0.06-0.31 μM. It 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. This chemical inhibits Hodgkin's lymphoma cells (KM-H2, L428, L540, L540cy, L591, L1236 and DEV) with IC50 from 0.24-0.8 μM. It shows low activity in lymphocytes from healthy individuals. This compound inhibits the constitutive activity of NF-κB despite defective IκB. It 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. This chemical 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. It is considerably more active than 17-AAG against adrenocortical carcinoma H295R, both in vitro and in vivo. The cytotoxic activity of this compound 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. It is also active in 17-AAG resistant cell lines (NIH-H69, MES SA Dx5, NCI-ADR-RES, Nalm6 and etc.).
Saggio chinasico	Saggio di legame Hsp90
Saggio chinasico	Per le misurazioni di competizione per polarizzazione di fluorescenza, la sonda FITC-geldanamicina (20 nM) viene ridotta con 2 mM di TCEP a temperatura ambiente per 3 ore, dopodiché la soluzione viene aliquotata e conservata a -80 °C fino all'uso. Hsp90α umana ricombinante (0,8 nM) e FITC-geldanamicina ridotta (2 nM) vengono incubate in una micropiastra a 96 pozzetti a temperatura ambiente per 3 ore in presenza di tampone di saggio contenente 20 mM HEPES (pH 7,4), 50 mM KCl, 5 mM MgCl₂, 20 mM Na₂MoO₄, 2 mM DTT, 0,1 mg/mL BGG e 0,1% (v/v) CHAPS. Dopo questa preincubazione, questo composto in DMSO al 100% viene quindi aggiunto a concentrazioni finali da 0,2 nM a 10 μM (volume finale 100 μL, 2% DMSO). La reazione viene incubata per 16 ore a temperatura ambiente e la fluorescenza viene quindi misurata in un lettore di piastre Analyst, eccitazione = 485 nm, emissione = 535 nm. I controlli alti e bassi non contenevano questo composto chimico o non Hsp90, rispettivamente. I dati vengono adattati a una curva a quattro parametri e viene generata l'IC50.
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. This compound effectively inhibits growth of L540cy tumor at a dose of 120 mg/kg. It significantly enhances antitumor growth effect of radiation in JHU12 xenograft.
Riferimenti	[1] https://pubmed.ncbi.nlm.nih.gov/19372565/ [2] https://pubmed.ncbi.nlm.nih.gov/19671844/ [3] https://pubmed.ncbi.nlm.nih.gov/19662650/ [4] https://pubmed.ncbi.nlm.nih.gov/19676042/

Informazioni sullo studio clinico (Clinical Trial Information)

(dati da https://clinicaltrials.gov, aggiornato il 2024-05-22)

Numero NCT	Reclutamento	Condizioni	Sponsor/Collaboratori	Data di inizio	Fasi
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

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

BIIB021 HSP Inibitore

Peso molecolare: 318.76

Controllo Qualità (Quality Control)

Coltura cellulare, trattamento e concentrazione di lavoro
(Cell Culture, Treatment & Working Concentration)

Informazioni chimiche, conservazione e stabilità (Chemical Information, Storage & Stability)

Solubilità (Solubility)

Calcolatore di Molarità

Calcolatore di formulazione in vivo (Soluzione chiara)

Meccanismo d'azione (Mechanism of Action)

Informazioni sullo studio clinico (Clinical Trial Information)

BIIB021 HSP Inibitore

Peso molecolare: 318.76

Controllo Qualità (Quality Control)

Coltura cellulare, trattamento e concentrazione di lavoro (Cell Culture, Treatment & Working Concentration)

Informazioni chimiche, conservazione e stabilità (Chemical Information, Storage & Stability)

Solubilità (Solubility)

Calcolatore di Molarità

Calcolatore di formulazione in vivo (Soluzione chiara)

Meccanismo d'azione (Mechanism of Action)

Informazioni sullo studio clinico (Clinical Trial Information)

Coltura cellulare, trattamento e concentrazione di lavoro
(Cell Culture, Treatment & Working Concentration)