Neratinib

別名：HKI-272

製品コード：S2150 純度：99.94%

Neratinib is a highly selective HER2 and EGFR inhibitor with IC50 of 59 nM and 92 nM in cell-free assays; weakly inhibits KDR and Src, no significant inhibition to Akt, CDK1/2/4, IKK-2, MK-2, PDK1, c-Raf and c-Met. Phase 3.

CAS No. 698387-09-6

サイズ	価格(税別)	在庫状況
5mg	JPY 22000	国内在庫あり
25mg	JPY 55500	国内在庫あり
100mg	JPY 118500	国内在庫あり
1g	JPY 448500	国内在庫なし(納期7~10日)

代表番号: 045-509-1970\|電子メール：[email protected] よく尋ねられる質問

文献中Selleckの製品使用例（99）

製品安全説明書

現在のバッチを見る：純度： 99.94%

99.94

Neratinib関連製品

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関連化合物ライブラリー	Kinase Inhibitor Library Tyrosine Kinase Inhibitor Library PI3K/Akt Inhibitor Library Cell Cycle compound library Angiogenesis Related compound Library	もっと見る

シグナル伝達経路

HER2シグナル伝達経路

HER2阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	活性情報	PMID
SKBR	Growth Inhibition Assay	0.01-100 nM	3-7 d	inhibits cell growth in time and dose dependent manner	21487605
Sf9	Function assay		10 mins	Inhibition of human wild type EGFR expressed in Sf9 cells using [gamma32P]-ATP after 10 mins by scintillation counting, IC50 = 0.0025 μM.	24900643
Sf9	Function assay		10 mins	Inhibition of human EGFR T790M/L858R mutant expressed in Sf9 cells using [gamma32P]-ATP after 10 mins by scintillation counting, IC50 = 0.066 μM.	24900643
BAF3	Function assay		72 hrs	Inhibition of Tel-fused IGF1R (unknown origin) expressed in mouse BAF3 cells assessed as growth inhibition after 72 hrs by CellTiter-Glo assay, GI50 = 0.19 μM.	28282122
BAF3	Function assay		72 hrs	Inhibition of Tel-fused INSR (unknown origin) expressed in mouse BAF3 cells assessed as growth inhibition after 72 hrs by CellTiter-Glo assay, GI50 = 0.29 μM.	28282122
BAF3	Growth inhibition assay		72 hrs	Growth inhibition of mouse BAF3 cells after 72 hrs by CellTiter-Glo assay, GI50 = 1.9 μM.	28282122
SKBR3	Growth Inhibition Assay			IC50=0.0075 ± 0.005 μM	23816254
BT474	Growth Inhibition Assay			IC50=0.00323 ± 0.00075 μM	23816254
CAL-51	Growth Inhibition Assay			IC50=1.89 μM	24009064
KPL-1	Growth Inhibition Assay			IC50=1.89 μM	24009064
BT-549	Growth Inhibition Assay			IC50=1.14 μM	24009064
MDA-MB-157	Growth Inhibition Assay			IC50=1.12 μM	24009064
MDA-MB-231	Growth Inhibition Assay			IC50=1.00 μM	24009064
UACC-732	Growth Inhibition Assay			IC50=0.65 μM	24009064
HCC1143	Growth Inhibition Assay			IC50=0.54 μM	24009064
HCC1937	Growth Inhibition Assay			IC50=0.50 μM	24009064
HCC1395	Growth Inhibition Assay			IC50=0.49 μM	24009064
HCC1806	Growth Inhibition Assay			IC50=0.44 μM	24009064
MDA-MB-415	Growth Inhibition Assay			IC50=0.42 μM	24009064
MCF-7	Growth Inhibition Assay			IC50=0.41 μM	24009064
MDA-MB-436	Growth Inhibition Assay			IC50=0.41 μM	24009064
CAMA-1	Growth Inhibition Assay			IC50=0.37 μM	24009064
MDA-MB-468	Growth Inhibition Assay			IC50=0.33 μM	24009064
MDA-MB-435	Growth Inhibition Assay			IC50=0.33 μM	24009064
HCC38	Growth Inhibition Assay			IC50=0.25 μM	24009064
MDA-MB-134	Growth Inhibition Assay			IC50=0.17 μM	24009064
T-47D	Growth Inhibition Assay			IC50=0.16 μM	24009064
EFM-19	Growth Inhibition Assay			IC50=0.11 μM	24009064
HCC1187	Growth Inhibition Assay			IC50=0.10 μM	24009064
MDA-MB-453	Growth Inhibition Assay			IC50=0.09 μM	24009064
BT-20	Growth Inhibition Assay			IC50=0.07 μM	24009064
HCC70	Growth Inhibition Assay			IC50=0.03 μM	24009064
ZR-75-1	Growth Inhibition Assay			IC50=0.03 μM	24009064
SUM-190	Growth Inhibition Assay			IC50=0.01 μM	24009064
SUM-225	Growth Inhibition Assay			IC50=0.01 μM	24009064
UACC-893	Growth Inhibition Assay			IC50<0.005 μM	24009064
UACC-812	Growth Inhibition Assay			IC50<0.005 μM	24009064
SK-BR-3	Growth Inhibition Assay			IC50<0.005 μM	24009064
MDA-MB-361	Growth Inhibition Assay			IC50<0.005 μM	24009064
MDA-MB-175	Growth Inhibition Assay			IC50<0.005 μM	24009064
HCC1954	Growth Inhibition Assay			IC50<0.005 μM	24009064
HCC1569	Growth Inhibition Assay			IC50<0.005 μM	24009064
EFM-192A	Growth Inhibition Assay			IC50<0.005 μM	24009064
BT-474	Growth Inhibition Assay			IC50<0.005 μM	24009064
MDAMB453	Growth Inhibition Assay			IC50=1.59 ± 0.179 μM	23816254
KB	Growth Inhibition Assay			IC50=4.13 ± 0.47 μM	22491935
KBv200	Growth Inhibition Assay			IC50=6.03 ± 0.64 μM	22491935
MCF-7	Growth Inhibition Assay			IC50=3.30 ± 0.41 μM	22491935
MCF-7/Adr	Growth Inhibition Assay			IC50= 2.88 ± 0.30 μM	22491935
MCF-7	Growth Inhibition Assay			IC50=3.02 ± 0.34 μM	22491935
MCF-7/FLV1000	Growth Inhibition Assay			IC50=7.09 ± 0.71 μM	22491935
HL60	Growth Inhibition Assay			IC50=2.26 ± 0.23 μM	22491935
HL60/Adr	Growth Inhibition Assay			IC50=1.42 ± 0.15 μM	22491935
HEK293/pcDNA3.1	Growth Inhibition Assay			IC50=5.29 ± 0.53 μM	22491935
HEK293/ABCB1	Growth Inhibition Assay			IC50=6.91 ± 0.70 μM	22491935
L858R(EGFR)	Cell Viability Assay			decreases cell viability in time and dose dependent manner	17311002
L858R/T790M(EGFR)	Cell Viability Assay			decreases cell viability in time and dose dependent manner	17311002
G776insV_G/C	Cell Viability Assay			decreases cell viability in time and dose dependent manner	17311002
wild-type	Cell Viability Assay			decreases cell viability in time and dose dependent manner	17311002
A775insYVMA	Cell Viability Assay			decreases cell viability in time and dose dependent manner	17311002
G776insV_G/L	Cell Viability Assay			decreases cell viability in time and dose dependent manner	17311002
P780insGSP	Cell Viability Assay			decreases cell viability in time and dose dependent manner	17311002
NCI-H1781	Growth Inhibition Assay			inhibits cell growth in time and dose dependent manner	16818618
HCC827	Growth Inhibition Assay			inhibits cell growth in time and dose dependent manner	16818618
H3255	Growth Inhibition Assay			inhibits cell growth in time and dose dependent manner	16818618
NCI-H1975	Growth Inhibition Assay			inhibits cell growth in time and dose dependent manner	16818618
A549	Growth Inhibition Assay			inhibits cell growth in time and dose dependent manner	16818618
3T3	Growth Inhibition Assay			IC50=700 ± 78 nM	15173008
3T3/neu	Growth Inhibition Assay			IC50=3 ± 0.14 nM	15173008
SK-Br-3	Growth Inhibition Assay			IC50=2 ± 0.18 nM	15173008
BT 474	Growth Inhibition Assay			IC50=2 ± 0.06 nM	15173008
A431	Growth Inhibition Assay			IC50=81 ± 9 nM	15173008
MDA-MB-435	Growth Inhibition Assay			IC50=960 ± 165 nM	15173008
SW620	Growth Inhibition Assay			IC50=690 ± 84 nM	15173008
SKBR3	Function assay			Inhibition of human Her2 in SKBR3 cells, EC50 = 0.002 μM.	18077425
BT474	Function assay			Inhibition of human Her2 in BT474 cells, EC50 = 0.002 μM.	18077425
A431	Function assay			Inhibition of human Her2 in A431 cells, EC50 = 0.081 μM.	18077425
SW620	Function assay			Inhibition of human Her2 in SW620 cells, EC50 = 0.69 μM.	18077425
BA/F3	Cytotoxicity assay			Cytotoxicity against mouse BA/F3 cells expressing EGFR L858R mutant, IC50 = 0.0035 μM.	19239229
BA/F3	Cytotoxicity assay			Cytotoxicity against mouse BA/F3 cells expressing EGFR L858R/T790M mutant, IC50 = 0.18 μM.	19239229
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生物活性

製品説明

Targets

HER2 ^[1] (Cell-free assay)	EGFR ^[1] (Cell-free assay)	KDR ^[1] (Cell-free assay)	Src ^[1] (Cell-free assay)
59 nM	92 nM	800 nM	1.4 μM

In Vitro
In vitro	Neratinib weakly inhibits tyrosine kinases KDR and Src with IC50 of 0.8 μM and 1.4 μM, respectively, being 14- and 24-fold less active compared with HER2. Neratinib displays no activity against other serine-threonine kinases such as Akt, cyclin D1/cdk4, cyclin E/cdk2, cyclin B1/cdk1, IKK-2, MK-2, PDK1, c-Raf, and Tpl-2, as well as the tyrosine kinase c-Met. Neratinib selectively inhibits the proliferation of 3T3 cells transfected with the HER2 (3T3/neu), as well as two other HER-2-overexpressing SK-Br-3 and BT474 cells with IC50 values of 2-3 nM, displaying >230-fold potency compared with non-transfected 3T3 cells as well as MDA-MB-435 and SW620 which are EGFR- and HER2-negative. Neratinib also inhibits the proliferation of EGFR-dependent A431 cells with an IC50 of 81 nM. Neratinib reduces HER2 receptor autophosphorylation in BT474 cells with an IC50 of 5 nM, and EGF-dependent phosphorylation of EGFR in A431 cells with IC50 of 3 nM. Blocking of HER-2 by Neratinib results in inhibition of downstream MAPK and Akt pathways with IC50 of 2 nM, more potently than Trastuzumab. Neratinib inhibits the cyclin D1 expression and the phosphorylation of the Rb-susceptibility gene production in BT474 cells with IC50 of 9 nM, leading to G1-S arrest and ultimately decreased cell proliferation. ^[1]
Kinase Assay	Cell-free autophosphorylation assay using time-resolved fluorometry
Kinase Assay	Neratinib is prepared as 10 mg/mL stocks in DMSO and diluted in 25 mM HEPES (pH 7.5; 0.002 ng/mL-20 μg/mL). Purified recombinant COOH-terminal fragments of HER2 (amino acids 676-1255) or epidermal growth factor receptor (EGFR) (amino acids 645-1186) [diluted in 100 mM HEPES (pH 7.5) and 50% glycerol] is incubated with increasing concentrations of Neratinib in 4 mM HEPES (pH 7.5), 0.4 mM MnCl₂, 20 μM sodium vanadate, and 0.2 mM DTT for 15 minutes at room temperature in 96-well ELISA plates. The kinase reaction is initiated by the addition of 40 μM ATP and 20 mM MgCl₂ and allowed to proceed for 1 hour at room temperature. Plates are washed, and phosphorylation is detected using Europium-labeled anti-phospho-tyrosine antibodies (15 ng/well). After washing and enhancement steps, signal is detected using a Victor2 fluorescence reader (excitation wavelength 340 nm, emission wavelength 615 nm). The concentration of Neratinib that inhibits receptor phosphorylation by 50% (IC50) is calculated from inhibition curves.
細胞実験	細胞株	3T3, 3T3/neu, A431, BT474, SK-Br-3, MDA-MB-435, and SW480
	濃度	Dissolved in DMSO, final concentrations 0.5 ng/mL-5 μg/mL
	反応時間	2 or 6 days
	実験の流れ	Cells are exposed to various concentrations of Neratinib for 2, or 6 days. Cell proliferation is determined using sulforhodamine B, a protein binding dye. Briefly, cells are fixed with 10% trichloroacetic acid and washed extensively with water. Cells are then stained with 0.1% sulforhodamine B and washed in 5% acetic acid. Protein-associated dye is solubilized in 10 mM Tris, and absorbance is measured at 450 nM. The concentration of Neratinib that inhibits cell proliferation by 50% (IC50) is determined from inhibition curves.
実験結果図	Methods	Biomarkers	結果図	PMID
	Western blot	p-ERBB2 / ERBB2 / p-ERBB3 / ERBB3 / p-EGFR / p-90RSK pHER2 / HER2 / pAKT / AKT / pERK / ERK		30118499
	Growth inhibition assay	Cell viability		30118499

In Vivo
In Vivo	Oral administration of Neratinib significantly inhibits the growth of 3T3/neu xenografts, with inhibition of 34%, 53%, 98%, and 98% at dose of 10, 20, 40, and 80 mg/kg/day, respectively. Consistent with the inhibition of HER-2 phosphorylation by 84% within 1 hour of administration at 40 mg/kg/day, Neratinib inhibits the growth of BT474 xenografts by 70-82%, 67%, and 93% at dose of 5, 10, and 40 mg/kg/day, respectively. Neratinib is also effective against SK-OV-3 xenografts with inhibition of 31% and 85% at 5 and 60 mg/kg/day, respectively. Neratinib is less potent against EGFR-dependent A431 xenografts than HER-2-dependent tumors, with 32% and 44% inhibition at 5 and 20 mg/kg/day, respectively. Neratinib displays little activity against MCF-7 and MX-1 xenografts expressing low levels of HER-2 and EGFR, with only 28% inhibition at 80 mg/kg/day, suggesting that Neratinib has selective activity for cells expressing HER-2 or EGFR. ^[1]
動物実験	動物モデル	Female athymic (nude) mice implanted s.c. with 3T3/neu, BT474, MCF-7, or SK-OV-3 cells
	投与量	~80 mg/kg/day
	投与経路	Gavage

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-05-22)
NCT05388149	Recruiting	Breast Cancer\|HER2-positive Breast Cancer	University Health Network Toronto	December 6 2022	Phase 2
NCT05252988	Recruiting	Early-stage Breast Cancer\|HER2 Positive Breast Cancer\|Hormone Receptor Positive	Spanish Breast Cancer Research Group\|Puma Biotechnology Inc.\|Pierre Fabre Laboratories	August 31 2022	Phase 2
NCT04856475	Withdrawn	Breast Cancer\|Brain Metastases	Jules Bordet Institute	November 24 2021	Phase 2
NCT04781374	Withdrawn	Metastatic Prostate Adenocarcinoma\|Castration-resistant Prostate Cancer\|Prostate Cancer\|Prostate Cancer Metastatic	Beth Israel Deaconess Medical Center\|Puma Biotechnology Inc.\|Dana-Farber Cancer Institute	May 21 2021	Phase 2

参考
[1] Rabindran SK, et al. Cancer Res, 2004, 64(11), 3958-3965.

参考

[1] Rabindran SK, et al. Cancer Res, 2004, 64(11), 3958-3965.

化学情報

分子量	557.04	化学式	C₃₀H₂₉ClN₆O₃
CAS No.	698387-09-6	SDF	Download Neratinib SDFをダウンロードする
Smiles	CCOC1=C(C=C2C(=C1)N=CC(=C2NC3=CC(=C(C=C3)OCC4=CC=CC=N4)Cl)C#N)NC(=O)C=CCN(C)C
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1年-80°Cin solvent
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1个月-20°Cin solvent

In vitro
Batch:

DMSO : 6 mg/mL ( (10.77 mM)；吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Water : Insoluble

Ethanol : Insoluble

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機

実験計算

モル濃度計算器

質量	濃度	体積	分子量
=	×	×

希釈計算器分子量計算器

投与溶液組成計算機(クリア溶液)

ステップ１：実験データを入力してください。（実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します）

投与量 mg/kg 動物平均体重 g 投与体積（動物毎）μL 動物数匹

ステップ２：投与溶媒の組成を入力してください。（ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください）

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

計算結果：

投与溶媒濃度： mg/ml;

DMSOストック溶液調製方法： mg 試薬を μL DMSOに溶解する（濃度 mg/mL, 注：濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法：Take μL DMSOストック溶液に μL PEG300，を加え、完全溶解後μL Tween 80，を加えて完全溶解させた後 μL ddH₂O，を加え完全に溶解させます。

投与溶媒調製方法：μL DMSOストック溶液に μL Corn oil，を加え、完全溶解。

注意：１.ストック溶液に沈殿、混濁などがないことをご確認ください；
２.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

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