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Reagenzien und Instrumente für die Immunologie Zellbiologie und Molekularbiologie

Alpelisib [1217486-61-7]

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Katalog-Nummer HY-15244-5mg

Size : 5mg

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Telefonnummer : +1 850 650 7790

Marke : MedChemExpress

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Contact local distributor :

Telefonnummer : +1 850 650 7790

Beschreibung

Alpelisib (BYL-719) is a potent, selective, and orally active PI3Kα inhibitor. Alpelisib (BYL-719) shows efficacy in targeting PIK3CA-mutated cancer. Alpelisib (BYL-719) also inhibits p110α/p110γ/p110δ/p110β with IC₅₀s of 5/250/290/1200 nM, respectively. Antineoplastic activity^[1]^[2]^[3].

IC₅₀ & Target^[1]^[2]

p110α

5 nM (IC₅₀)

p110γ

250 nM (IC₅₀)

p110δ

290 nM (IC₅₀)

p110β

1200 nM (IC₅₀)

p110α-H1047R

4 nM (IC₅₀)

p110α-E545K

4 nM (IC₅₀)

Cellular Effect

Cell Line	Type	Value	Description	References
Kasumi 1	IC₅₀	0.44 μM Compound: Alpelisib	Antiproliferative activity against human Kasumi 1 cells assessed as cell growth inhibition incubated for 72 hrs by MTT assay Antiproliferative activity against human Kasumi 1 cells assessed as cell growth inhibition incubated for 72 hrs by MTT assay	[PMID: 37126967]
MCF7	IC₅₀	0.43 μM Compound: Alpelisib	Antiproliferative activity against human MCF7 cells assessed as inhibition of cell growth incubated for 72 hrs by CCK8 assay Antiproliferative activity against human MCF7 cells assessed as inhibition of cell growth incubated for 72 hrs by CCK8 assay	[PMID: 35834807]
MCF7	IC₅₀	530 nM Compound: 2; BYL719	Antiproliferation activity against human MCF7 cells assessed as reduction in cell viability incubated for 7 days by Cell-titer Glo reagent based assay Antiproliferation activity against human MCF7 cells assessed as reduction in cell viability incubated for 7 days by Cell-titer Glo reagent based assay	[PMID: 33356246]
MDA-MB-231	IC₅₀	62.9 μM Compound: Alpesilib	Antiproliferative activity against human MDA-MB-231 cells assessed as cell viability after 24 hrs Antiproliferative activity against human MDA-MB-231 cells assessed as cell viability after 24 hrs	[PMID: 33139111]
MGC-803	IC₅₀	0.43 μM Compound: Alpelisib	Antiproliferative activity against human MGC-803 cells assessed as inhibition of cell growth incubated for 72 hrs by CCK8 assay Antiproliferative activity against human MGC-803 cells assessed as inhibition of cell growth incubated for 72 hrs by CCK8 assay	[PMID: 35834807]
Rat1	IC₅₀	0.074 μM Compound: 8, NVP-BYL719	Inhibition of N-terminal myristoylated P110alpha (unknown origin)-mediated AKT phosphorylation at Ser473 expressed in rat Rat1 cells by ELISA Inhibition of N-terminal myristoylated P110alpha (unknown origin)-mediated AKT phosphorylation at Ser473 expressed in rat Rat1 cells by ELISA	[PMID: 23726034]
Rat1	IC₅₀	0.074 μM Compound: 1, BYL719	Inhibition of myristoylated human P110alpha expressed in Rat1 cells assessed as inhibition of Akt phosphorylation at Serine 473 by Western blot analysis Inhibition of myristoylated human P110alpha expressed in Rat1 cells assessed as inhibition of Akt phosphorylation at Serine 473 by Western blot analysis	[PMID: 26164189]
Rat1	IC₅₀	1.2 μM Compound: 8, NVP-BYL719	Inhibition of N-terminal myristoylated P110delta (unknown origin)-mediated AKT phosphorylation at Ser473 expressed in rat Rat1 cells by ELISA Inhibition of N-terminal myristoylated P110delta (unknown origin)-mediated AKT phosphorylation at Ser473 expressed in rat Rat1 cells by ELISA	[PMID: 23726034]
Rat1	IC₅₀	1.2 μM Compound: 1, BYL719	Inhibition of myristoylated human P110delta expressed in Rat1 cells assessed as inhibition of Akt phosphorylation at Serine 473 by Western blot analysis Inhibition of myristoylated human P110delta expressed in Rat1 cells assessed as inhibition of Akt phosphorylation at Serine 473 by Western blot analysis	[PMID: 26164189]
Rat1	IC₅₀	2.2 μM Compound: 8, NVP-BYL719	Inhibition of N-terminal myristoylated P110beta (unknown origin)-mediated AKT phosphorylation at Ser473 expressed in rat Rat1 cells by ELISA Inhibition of N-terminal myristoylated P110beta (unknown origin)-mediated AKT phosphorylation at Ser473 expressed in rat Rat1 cells by ELISA	[PMID: 23726034]
Rat1	IC₅₀	2.2 μM Compound: 1, BYL719	Inhibition of myristoylated human P110beta expressed in Rat1 cells assessed as inhibition of Akt phosphorylation at Serine 473 by Western blot analysis Inhibition of myristoylated human P110beta expressed in Rat1 cells assessed as inhibition of Akt phosphorylation at Serine 473 by Western blot analysis	[PMID: 26164189]
SJRH30	IC₅₀	7.6 μM Compound: BYL719	Antiproliferative activity against human Rh30 cells assessed as reduction in cell viability after 72 hrs by sulforhodamine B assay Antiproliferative activity against human Rh30 cells assessed as reduction in cell viability after 72 hrs by sulforhodamine B assay	[PMID: 33109399]
T47D	IC₅₀	0.1 μM Compound: Alpelisib	Antiproliferative activity against human T47D cells expressing PIK3CA mutant assessed as cell growth inhibition incubated for 72 hrs by MTT assay Antiproliferative activity against human T47D cells expressing PIK3CA mutant assessed as cell growth inhibition incubated for 72 hrs by MTT assay	[PMID: 37126967]
T47D	IC₅₀	420 nM Compound: 2; BYL719	Antiproliferation activity against human T47D cells assessed as reduction in cell viability incubated for 7 days by Cell-titer Glo reagent based assay Antiproliferation activity against human T47D cells assessed as reduction in cell viability incubated for 7 days by Cell-titer Glo reagent based assay	[PMID: 33356246]

In Vitro

Alpelisib (BYL-719) potently inhibits the 2 most common PIK3CA somatic mutations (H1047R, E545K; IC₅₀s~4 nM). Alpelisib potently inhibits Akt phosphorylation in cells transformed with PI3Kα (IC₅₀=74±15 nM) and shows significant reduced inhibitory activity in PI3Kβ or PI3Kδ isoforms transformed cells (≥15-fold compared with PI3Kα)^[2].
Alpelisib (BYL-719, 0-50 μM; 72 hours) inhibits the cell growth of osteosarcoma cell lines MG63, HOS, POS-1 and MOS-J in a dose-dependent manner^[3].
Alpelisib (BYL-719) significantly alters the distribution of cell cycle phases. Alpelisib (BYL-719, 25 μM; 18 hours) induces a cell cycle arrest in the G0/G1 phase of human and murine osteosarcoma cell lines^[3].

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

Cell Proliferation Assay^[3]

Cell Line:	MG63, HOS, POS-1, MOS-J
Concentration:	10, 20, 30, 40, 50 μM
Incubation Time:	72 hours
Result:	Inhibited the cell growth of all osteosarcoma cell lines tested in a dose-dependent manner with IC₅₀s of 6-15 µM and with IC₉₀s of 24-42 µM.

Cell Cycle Analysis^[3]

Cell Line:	MG63, HOS, POS-1, MOS-J
Concentration:	25 μM
Incubation Time:	18 hours
Result:	Induced a cell cycle arrest in the G0/G1 phase of human and murine osteosarcoma cell .

In Vivo

Alpelisib has moderate terminal elimination half-life (t_1/2=2.9±0.2 h) for rat (1 mg/kg, iv) ^[1].
Alpelisib (BYL-719) (12.5 mg/kg and 50 mg/kg for C57Bl/6J mice; 50 mg/kg for female Rj:NMRI-nude mice; oral administration; daily) significantly reduces tumor volumes and deposition of ectopic bone matrix^[3].

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

Animal Model:	A 5-week-old female Rj:NMRI-nude mice with human HOS-MNNG osteosarcoma cells; A 5-week-old male C57Bl/6J mice with mouse MOS-J osteosarcoma cells^[3]
Dosage:	12.5 mg/kg and 50 mg/kg for C57Bl/6J mice; 50 mg/kg for female Rj:NMRI-nude mice
Administration:	Oral administration; daily; 22 or 29 days for C57Bl/6J mice or Rj:NMRI-nude mice
Result:	Significantly reduced tumor volumes and simultaneously reduced tumor growth.

Animal Model:	Female Sprague Dawley rats ^[1]
Dosage:	1 mg/kg (Pharmacokinetic Analysis)
Administration:	I.V.
Result:	t_1/2=2.9±0.2 hours.

Klinische Studie

Molekulargewicht

441.47

Formel

C₁₉H₂₂F₃N₅O₂S

CAS. Nr.

1217486-61-7

Appearance

Solid

Color

Off-white to light yellow

SMILES

CC(N=C(S1)NC(N2CCC[C@H]2C(N)=O)=O)=C1C3=CC(C(C)(C(F)(F)F)C)=NC=C3

Versand

Room temperature in continental US; may vary elsewhere.

Speicherung

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

Lösungsmittel & Löslichkeit

In Vitro:

DMSO : 83.33 mg/mL (188.76 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	2.2652 mL	11.3258 mL	22.6516 mL
5 mM	0.4530 mL	2.2652 mL	4.5303 mL
10 mM	0.2265 mL	1.1326 mL	2.2652 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.

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: 5% DMSO 40% PEG300 5% Tween-80 50% Saline
Solubility: ≥ 5 mg/mL (11.33 mM); Clear solution
Protocol 2

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: 2.08 mg/mL (4.71 mM); Suspended solution; Need ultrasonic

This protocol yields a suspended solution of 2.08 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 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 3

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.08 mg/mL (4.71 mM); Clear solution

This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 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.
Protocol 4

Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.08 mg/mL (4.71 mM); Clear solution

This protocol yields a clear solution of ≥ 2.08 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 (20.8 mg/mL) to 900 μL Corn oil, and mix evenly.

For the following dissolution methods, please prepare the working solution directly. It is recommended to prepare fresh solutions and use them promptly within a short period of time.
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: 0.5% Methyl cellulose/0.5% Tween-80 in Saline water
Solubility: 10 mg/mL (22.65 mM); Suspension solution; Need ultrasonic
Protocol 2

Add each solvent one by one: 1% CMC/0.5% Tween-80 in Saline water
Solubility: 10 mg/mL (22.65 mM); Suspension solution; Need ultrasonic

Reinheit & Dokumentation

Purity: 99.95%

Data Sheet (282 KB) SDS (393 KB)

COA (0 KB) HNMR (191 KB) Elemental Analysis Report (110 KB)

Handling Instructions (2659 KB)

Verweise

[1]. Furet P, et al. Discovery of NVP-BYL719 a potent and selective phosphatidylinositol-3 kinase alpha inhibitor selected for clinical evaluation. Bioorg Med Chem Lett. 2013 Jul 1;23(13):3741-8. [Content Brief]

[2]. Fritsch C, et al. Characterization of the novel and specific PI3Kα inhibitor NVP-BYL719 and development of the patient stratification strategy for clinical trials. Mol Cancer Ther. 2014 May;13(5):1117-29. [Content Brief]

[3]. Gobin B, et al. BYL719, a new α-specific PI3K inhibitor: single administration and in combination with conventional chemotherapy for the treatment of osteosarcoma. Int J Cancer. 2015 Feb 15;136(4):784-96. [Content Brief]

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Alpelisib [1217486-61-7]

Katalog-Nummer HY-15244-5mg

Contact local distributor :

Marke : MedChemExpress

Contact local distributor :

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