HY-10192-5mg | NVP-TAE 684 [761439-42-3] Clinisciences

Descripciòn

NVP-TAE 684 (TAE 684) is a highly potent and selective ALK inhibitor, which blocks the growth of ALCL-derived and ALK-dependent cell lines with IC₅₀ values between 2 and 10 nM^[1].

IC₅₀ & Target

IC50: 2-10 nM (ALK-dependent cell lines)^[1]

Cellular Effect

Cell Line	Type	Value	Description	References
BaF3	IC₅₀	0.001 μM Compound: 1, TAE684	Cytotoxicity against mouse BAF3 cells expressing Tel-ALK after 48 hrs by CellTiter-Glo assay Cytotoxicity against mouse BAF3 cells expressing Tel-ALK after 48 hrs by CellTiter-Glo assay	[PMID: 21572589]
BaF3	IC₅₀	0.02 μM Compound: 1, TAE684	Cytotoxicity against mouse BAF3 cells expressing EML4-ALK after 48 hrs by MTS assay Cytotoxicity against mouse BAF3 cells expressing EML4-ALK after 48 hrs by MTS assay	[PMID: 21572589]
BaF3	IC₅₀	0.06 μM Compound: 1, TAE684	Cytotoxicity against mouse BAF3 cells expressing ALK F1174L mutant coexpressing EML4 after 48 hrs by MTS assay Cytotoxicity against mouse BAF3 cells expressing ALK F1174L mutant coexpressing EML4 after 48 hrs by MTS assay	[PMID: 21572589]
BaF3	IC₅₀	0.08 μM Compound: 1, TAE684	Cytotoxicity against mouse BAF3 cells expressing ALK L1196M mutant coexpressing EML4 after 48 hrs by MTS assay Cytotoxicity against mouse BAF3 cells expressing ALK L1196M mutant coexpressing EML4 after 48 hrs by MTS assay	[PMID: 21572589]
BaF3	GI₅₀	1.1 μM Compound: 14; TAE684	Antiproliferative activity against mouse BAF3 cells after 72 hrs by CellTiter-Glo assay Antiproliferative activity against mouse BAF3 cells after 72 hrs by CellTiter-Glo assay	[PMID: 28850922]
BaF3	IC₅₀	1336 nM Compound: 4, TAE684	Cytotoxicity against mouse BAF3 cells after 2 to 3 days by luciferase reporter gene assay Cytotoxicity against mouse BAF3 cells after 2 to 3 days by luciferase reporter gene assay	[PMID: 23742252]
BaF3	IC₅₀	229.3 nM Compound: 18; TAE684	Cytotoxicity against mouse BaF3 cells expressing human EGFR C797S/del19 mutant assessed as inhibition of in cell viability measured after 72 hrs by CellTiter-Glo assay Cytotoxicity against mouse BaF3 cells expressing human EGFR C797S/del19 mutant assessed as inhibition of in cell viability measured after 72 hrs by CellTiter-Glo assay	[PMID: 33243531]
BaF3	IC₅₀	3 nM Compound: 1, TAE684	Cytotoxicity against mouse BAF3 cells expressing NPM-ALK after 48 hrs by CellTiter-Glo assay Cytotoxicity against mouse BAF3 cells expressing NPM-ALK after 48 hrs by CellTiter-Glo assay	[PMID: 21572589]
BaF3	IC₅₀	3.7 nM Compound: 4, TAE684	Inhibition of NPM-fused ALK (unknown origin) expressed in mouse BAF3 cells after 2 to 3 days by luciferase reporter gene assay Inhibition of NPM-fused ALK (unknown origin) expressed in mouse BAF3 cells after 2 to 3 days by luciferase reporter gene assay	[PMID: 23742252]
BaF3	IC₅₀	340.7 nM Compound: 18; TAE684	Cytotoxicity against mouse BaF3 cells expressing human EGFR C797S/T790M/del19 mutant assessed as inhibition of in cell viability measured after 72 hrs by CellTiter-Glo assay Cytotoxicity against mouse BaF3 cells expressing human EGFR C797S/T790M/del19 mutant assessed as inhibition of in cell viability measured after 72 hrs by CellTiter-Glo assay	[PMID: 33243531]
BaF3	IC₅₀	43.7 nM Compound: 4, TAE684	Inhibition of TEL-fused insulin receptor (unknown origin) expressed in mouse BAF3 cells after 2 to 3 days by luciferase reporter gene assay Inhibition of TEL-fused insulin receptor (unknown origin) expressed in mouse BAF3 cells after 2 to 3 days by luciferase reporter gene assay	[PMID: 23742252]
HEK293	IC₅₀	21.9 nM Compound: TAE684	Inhibition of LRRK2 G2019S and A2016T mutant expressed in HEK293 cells using nictide and ATP as substrate Inhibition of LRRK2 G2019S and A2016T mutant expressed in HEK293 cells using nictide and ATP as substrate	[PMID: 22335897]
HEK293	IC₅₀	6.1 nM Compound: TAE684	Inhibition of LRRK2 G2019S mutant expressed in HEK293 cells using nictide and ATP as substrate Inhibition of LRRK2 G2019S mutant expressed in HEK293 cells using nictide and ATP as substrate	[PMID: 22335897]
HEK293	IC₅₀	7.8 nM Compound: TAE684	Inhibition of wild-type LRRK2 expressed in HEK293 cells using nictide and [gamma32]ATP as substrate Inhibition of wild-type LRRK2 expressed in HEK293 cells using nictide and [gamma32]ATP as substrate	[PMID: 22335897]
HEK293	IC₅₀	93.3 nM Compound: TAE684	Inhibition of LRRK2 A2016T mutant expressed in HEK293 cells using nictide and ATP as substrate Inhibition of LRRK2 A2016T mutant expressed in HEK293 cells using nictide and ATP as substrate	[PMID: 22335897]
KARPAS-299	IC₅₀	< 10 nM Compound: TAE-684	Decrease in ALK phosphorylation in human Karpas299 cells after 4 hrs Decrease in ALK phosphorylation in human Karpas299 cells after 4 hrs	[PMID: 17185414]
KARPAS-299	IC₅₀	13 nM Compound: 2, NVP-TAE684	Antiproliferative activity against ALK-dependent human KARPAS299 cells after 72 hrs Antiproliferative activity against ALK-dependent human KARPAS299 cells after 72 hrs	[PMID: 24900831]
KARPAS-299	IC₅₀	14 nM Compound: 7; TAE684	Antiproliferative activity against human ALK-positive KARPAS299 cells assessed as reduction in cell viability measured after 72 hrs by CellTiter 96 aqueous one solution cell proliferation assay Antiproliferative activity against human ALK-positive KARPAS299 cells assessed as reduction in cell viability measured after 72 hrs by CellTiter 96 aqueous one solution cell proliferation assay	[PMID: 27144831]
KARPAS-299	IC₅₀	2 nM Compound: TAE-684	Antiproliferative activity against human Karpas299 cells assessed as luciferase expression after 72 hrs Antiproliferative activity against human Karpas299 cells assessed as luciferase expression after 72 hrs	[PMID: 17185414]
KARPAS-299	IC₅₀	2.4 nM Compound: 4, TAE684	Cytotoxicity against human KARPAS299 cells after 2 to 3 days by luciferase reporter gene assay Cytotoxicity against human KARPAS299 cells after 2 to 3 days by luciferase reporter gene assay	[PMID: 23742252]
KARPAS-299	IC₅₀	3 nM Compound: TAE-684	Induction of apoptosis in human Karpas299 cells by annexin V assay Induction of apoptosis in human Karpas299 cells by annexin V assay	[PMID: 17185414]
NCI-H1975	GI₅₀	0.72 μM Compound: 14; TAE684	Growth inhibition of human NCI-H1975 cells after 72 hrs by CellTiter-Glo assay Growth inhibition of human NCI-H1975 cells after 72 hrs by CellTiter-Glo assay	[PMID: 28850922]
SU-DHL-1	IC₅₀	2 nM Compound: TAE-684	Antiproliferative activity against human SUDHL1 cells assessed as luciferase expression after 72 hrs Antiproliferative activity against human SUDHL1 cells assessed as luciferase expression after 72 hrs	[PMID: 17185414]

In Vitro

TAE684 inhibits the proliferation of Ba/F3 NPM-ALK cells with an IC₅₀ of 3 nM, without affecting the survival of parental Ba/F3 cells at concentrations up to 1 μM. TAE684 inhibits STAT3 and STAT5 phosphorylation in a dose-dependent manner in both Ba/F3 NPM-ALK and Karpas-299 cells. TAE684 induces apoptosis and G1 phase arrest in NPM-ALK-expressing Ba/F3 cells and ALCL patient cell lines^[1].
NVP-TAE684 markedly reduces cell survival in both sensitive H3122 and H3122 CR cells, but has little to no effect on the viability of other, non-ALK-dependent cancer cell lines. NVP-TAE684 treatment of H3122 CR cells suppresses phosphorylation of ALK, AKT, and ERK and induces marked apoptosis.
TAE684 potently suppresses the survival of Ba/F3 cells expressing the EML4-ALK L1196M mutant^[2].
Neurite outgrowth induced by expression of the mALKR1279Q mutant is completely inhibited at 30 nM NVP-TAE684, which is comparable with the response seen with activated wt mALK^[3].

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

In Vivo

NVP-TAE684 suppresses lymphomagenesis in two independent models of ALK-positive ALCL and induces regression of established Karpas-299 lymphomas. TAE684 displays appreciable bioavailability and half-life in vivo.
TAE684 (1, 3, and 10 mg/kg. p.o.) significantly delays in lymphoma development and shows 100- to 1,000-fold reduction in luminescence signal. The TAE684- (10 mg/kg) treated group appeares healthy and does not display any signs of compound- or disease-related toxicity^[1].

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

Peso molecular

614.20

Fòrmula

C₃₀H₄₀ClN₇O₃S

No. CAS

761439-42-3

Appearance

Solid

Color

Light yellow to yellow

SMILES

O=S(C1=CC=CC=C1NC2=NC(NC3=CC=C(N4CCC(N5CCN(CC5)C)CC4)C=C3OC)=NC=C2Cl)(C(C)C)=O

Envío

Room temperature in continental US; may vary elsewhere.

Almacenamiento

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	2 years
	-20°C	1 year

Solvente y solubilidad

In Vitro:

DMSO : 7.69 mg/mL (12.52 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	1.6281 mL	8.1407 mL	16.2813 mL
5 mM	0.3256 mL	1.6281 mL	3.2563 mL
10 mM	0.1628 mL	0.8141 mL	1.6281 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.

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This equation is commonly abbreviated as: C₁V₁ = C₂V₂

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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: ≥ 0.77 mg/mL (1.25 mM); Clear solution

This protocol yields a clear solution of ≥ 0.77 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (7.7 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% (20% SBE-β-CD in Saline)
Solubility: ≥ 0.77 mg/mL (1.25 mM); Clear solution

This protocol yields a clear solution of ≥ 0.77 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (7.7 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.

In Vivo Dissolution Calculator

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Method for preparing stock solution: mg drug dissolved in μL DMSO (Stock solution concentration: mg/mL).

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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.

Pureza y Documentación

Purity: 99.27%

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SDS (393 KB)

COA (251 KB) LCMS (94 KB)

Instrucciones de manejo (2659 KB)

Referencias

[1]. Galkin AV, et al. Identification of NVP-TAE684, a potent, selective, and efficacious inhibitor of NPM-ALK. Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):270-5. [Content Brief]

[2]. Katayama R, et al. Therapeutic strategies to overcome PF-02341066 resistance in non-small cell lung cancers harboring the fusion oncogene EML4-ALK. Proc Natl Acad Sci U S A. 2011 May 3;108(18):7535-40. [Content Brief]

[3]. Schonherr C, Activating ALK mutations found in neuroblastoma are inhibited by PF-02341066 and NVP-TAE684. Biochem J. 2011 Dec 15;440(3):405-13. [Content Brief]

Ensayo celular ^[1]	Luciferase-expressing Karpas-299, SU-DHL-1, and Ba/F3 cells and transformed Ba/F3 stably expressing NPM-ALK, BCR-ABL, or TEL-kinase fusion constructs are plated in 384-well plates (25,000 cells per well) and incubated with serial dilutions of TAE684 or DMSO for 2-3 days. Luciferase expression is used as a measure of cell proliferation/survival and is evaluated with the Bright-Glo Luciferase Assay System. ICsub>50 values are generated by using XLFit software. MCE no ha confirmado la precisión de estos métodos independientemente. Son solo para referencia.
Administraciòn de animales ^[1]	For in vivo compound efficacy studies, treatment is initiated 72 h after tail vein injection of 1×10⁶ Karpas-299-, Ba/F3 NPM-ALK- or BCR-ABL-expressing cells into female Fox Chase SCIDBeige mice. Mice (n=10 per group) are administered either TAE684 resuspended in 10% 1-methyl-2-pyrrolidinone/90% PEG 300 solution at 1, 3, and 10 mg/kg once daily for 3 weeks or the vehicle solution at the same dosing schedule. Disease progression and compound efficacy is monitored weekly with bioluminescence imaging. To determine the efficacy of TAE684 on established disease, dosing is initiated on day 12, at which time the disease confirmed to be widespread by bioluminescence imaging. For analysis of downstream molecular effects in vivo, mice with established lymphomas are administered vehicle solution or TAE684 (10 mg/kg) for 3 days. At the end of treatment, mice are killed, and lymph nodes are extracted for immunoblotting and histological analysis. MCE no ha confirmado la precisión de estos métodos independientemente. Son solo para referencia.
Referencias	[1]. Galkin AV, et al. Identification of NVP-TAE684, a potent, selective, and efficacious inhibitor of NPM-ALK. Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):270-5. [Content Brief] [2]. Katayama R, et al. Therapeutic strategies to overcome PF-02341066 resistance in non-small cell lung cancers harboring the fusion oncogene EML4-ALK. Proc Natl Acad Sci U S A. 2011 May 3;108(18):7535-40. [Content Brief] [3]. Schonherr C, Activating ALK mutations found in neuroblastoma are inhibited by PF-02341066 and NVP-TAE684. Biochem J. 2011 Dec 15;440(3):405-13. [Content Brief]

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg

DMSO	1 mM	1.6281 mL	8.1407 mL	16.2813 mL	40.7034 mL
	5 mM	0.3256 mL	1.6281 mL	3.2563 mL	8.1407 mL
	10 mM	0.1628 mL	0.8141 mL	1.6281 mL	4.0703 mL

NVP-TAE 684 Related Classifications

Protein Tyrosine Kinase/RTK Apoptosis
Anaplastic lymphoma kinase (ALK) Apoptosis

NVP-TAE 684 [761439-42-3]

Referencia HY-10192-5mg

Contact local distributor :

Marca : MedChemExpress

Contact local distributor :

Calculadora de molaridad

Calculadora de dilución

Complete Stock Solution Preparation Table

NVP-TAE 684 Related Classifications

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Usted podría estar interesado también en los siguientes productos:

NVP-TAE 684 [761439-42-3]

Referencia HY-10192-5mg

Contact local distributor :

Marca : MedChemExpress

Contact local distributor :

NVP-TAE 684 Related Antibodies

Calculadora de molaridad

Calculadora de dilución

Complete Stock Solution Preparation Table

NVP-TAE 684 Related Classifications

Keywords:

Usted podría estar interesado también en los siguientes productos: