HER2

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研究领域

抑制剂选择性比较
溶解性比较

目录号	产品目录	溶解度(25°C)
目录号	产品目录	水	DMSO	酒精
S1028	Lapatinib (GW-572016) Ditosylate	<1 mg/mL	100 mg/mL	<1 mg/mL
S1011	Afatinib (BIBW2992)	<1 mg/mL	97 mg/mL	15 mg/mL
S2150	Neratinib (HKI-272)	<1 mg/mL	5 mg/mL	<1 mg/mL
S1019	Canertinib (CI-1033)	<1 mg/mL	2 mg/mL	9 mg/mL
S2111	Lapatinib	<1 mg/mL	100 mg/mL	<1 mg/mL
S5241	Lapatinib ditosylate monohydrate	-1 mg/mL	100 mg/mL	-1 mg/mL
S1167	CP-724714	<1 mg/mL	94 mg/mL	94 mg/mL
S2192	Sapitinib (AZD8931)	<1 mg/mL	40 mg/mL	<1 mg/mL
S1194	CUDC-101	<1 mg/mL	20 mg/mL	<1 mg/mL
S2216	Mubritinib (TAK 165)	<1 mg/mL	13 mg/mL	<1 mg/mL
S1056	AC480 (BMS-599626)	<1 mg/mL	113 mg/mL	20 mg/mL
S1486	AEE788 (NVP-AEE788)	<1 mg/mL	88 mg/mL	<1 mg/mL
S2752	HER2-Inhibitor-1	<1 mg/mL	100 mg/mL	3 mg/mL
S2784	TAK-285	<1 mg/mL	110 mg/mL	54 mg/mL
S2816	Tyrphostin AG 879	<1 mg/mL	36 mg/mL	3 mg/mL
S8362	Irbinitinib (ARRY-380, ONT-380)	<1 mg/mL	96 mg/mL	15 mg/mL
S2250	(-)-Epigallocatechin Gallate	23 mg/mL	72 mg/mL	83 mg/mL
S7810	Afatinib (BIBW2992) Dimaleate	<1 mg/mL	100 mg/mL	<1 mg/mL
S7358	Poziotinib (HM781-36B)	<1 mg/mL	98 mg/mL	<1 mg/mL

HER2抑制剂（21）
新HER2产品

产品目录	产品描述	文献引用	实验数据
A2007	Trastuzumab (anti-HER2) Trastuzumab (anti-HER2)曲妥珠单抗是人源重组的抗体抑制剂，与HER2的胞外区域相结合。 MW:145.53 KD。
A2008	Pertuzumab (anti-HER2) Pertuzumab (anti-HER2)是一种人源单价克隆抗体，抑制HER2二聚化、破坏HER2与其他HER家族成员结合的能力。MW: 148 KD。
S1028	Lapatinib (GW-572016) Ditosylate Lapatinib (GW-572016) Ditosylate是一种有效的EGFR 和 ErbB2抑制剂，在无细胞试验中IC50分别为10.8和9.2 nM。	Cancer Cell, 2012, 21(4):488-503 Gut, 2015, 10.1136/gutjnl-2014-309026 Sci Transl Med, 2015, 7(284):284ra57	Combination of NVP-AEW541 and lapatinib cooperatively inhibits the growth of NVP-AEW541 resistant murine rhabdomyosarcoma primary cell cultures with Igf1r/Her2 complexes. Cell viability assay for Naïve, untreated (U20325; A) and NVP-AEW541 innately resistant mouse rhabdomyosarcoma primary culture (U44676; B) treated with varying concentrations of NVP-AEW541, lapatinib, or a combination of both. Naïve cells (U20325) were sensitive to NVP-AEW541, but lapatinib had no cooperativity. In contrast, NVP-AEW541 at moderate doses increased cell growth in resistant cell cultures (U44676). However, this paradoxical effect was reduced by the addition of lapatinib, although lapatinib treatment alone had very little effect. C, the NVP-AEW541 resistant primary tumor cell line (U44676) was treated with DMSO, 5 μmol/L lapatinib, 5 μmol/L NVP-AEW541, and a combination of 5 μmol/L NVP-AEW541+lapatinib for 25 minutes and Western blot analysis was done on lysates for p-Igf1r and p-Her2.
S1011	Afatinib (BIBW2992) Afatinib (BIBW2992)不可逆地抑制EGFR/ErbB，包括EGFR(wt)，EGFR(L858R)，EGFR(L858R/T790M)，ErbB2（HER2）和ErbB4（HER4），在无细胞试验中IC50分别为0.5 nM，0.4 nM，10 nM，14 nM和1 nM。	Nature, 2016, 534(7609):647-51 Cancer Discov, 2015, 5(7):713-22 Cancer Discov, 2013, 3(2):168-81	Immunoblot analysis of serum starved H2030 cells pre-treated with 500 nM or 1 µM of gefitinib, crizotinib, CP-724714, or afatinib for 12 hr, followed by stimulation with EGF, HGF, NRG1, or their combination (50 ng/ml) for 10 min.
S2150	Neratinib (HKI-272) Neratinib (HKI-272)是一种高度选择性的HER2和EGFR抑制剂，在无细胞试验中IC50分别为59 nM 和 92 nM；微弱抑制KDR和Src，对Akt，CDK1/2/4，IKK-2，MK-2，PDK1，c-Raf和c-Met没有显著的抑制作用。Phase 3。	Cancer Discov, 2012, 2(5):458-71 Cancer Discov, 2013, 3(2):168-81 Cancer Discov, 2013, 3(2):224-37	Differential sensitivity of EGFR-mutant glioma and lung cancer cell lines to the irreversible EGFR inhibitors HKI-272 and CI-1033. C, HKI-272 is more potent than CI-1033 in blocking EGFR phosphorylation in SKMG3 cells with EGFR EC mutation. SKMG3 cells were treated with the indicated doses of CI-1033 or HKI-272, and whole lysates were analyzed by immunoblot with the indicated antibodies.
S1019	Canertinib (CI-1033) Canertinib (CI-1033)是一种泛ErbB抑制剂，作用于EGFR和ErbB2，IC50分别为1.5 nM和9.0 nM，但对PDGFR，FGFR，InsR，PKC，和CDK1/2/4等均无抑制活性。Phase 3。	Cancer Discov, 2012, 2(5):458-71 Cancer Lett, 2014, 344(1):90-100 J Exp Clin Cancer Res, 2018, 37(1):80
S2111	Lapatinib Lapatinib，以 Lapatinib Ditosylate的形式使用，是一种有效的EGFR和ErbB2抑制剂，在无细胞试验中IC50分别为10.2和9.8 nM。	Nature, 2016, 538(7626):477-482 Cancer Cell, 2015, 27(3):397-408 Cancer Cell, 2012, 21(4):488-503	Sensitivity to the ErbB1/ErbB2 inhibitor lapatinib is highest for cancer cells from late-stage tumors in culture (mean ± SEM, p = 0.04 or 0.02 as indicated, Student’s t test; values represent the averages of four experiments, each done in triplicate with primary cells from independent mice).
S5241^New	Lapatinib ditosylate monohydrate Lapatinib ditosylate is a dual tyrosine kinase inhibitor which interrupts the HER2/neu and epidermal growth factor receptor (EGFR) pathways, used for treatment of solid tumours such as breast and lung cancer.
S1167	CP-724714 CP-724714是一种有效的，选择性HER2/ErbB2抑制剂，IC50为10 nM，无细胞试验中比作用于EGFR，InsR，IRG-1R，PDGFR，VEGFR2，Abl，Src，c-Met等选择性高640多倍。Phase 2。	Cancer Res, 2014, 74(1):341-52 Cell Death Dis, 2014, 5:e1194 J Biol Chem, 2016, 291(16):8453-64	For MTT assays, cells (2,000 ~ 5,000 cells/well) were subcultured into 96-well plates according to their growth properties. Cell proliferation was assayed at 72 hr after treatment of CP-724714 by adding 20 μl of 5 mg/ml 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) solution per 100 μl of growth medium. After incubating for 3-4 h at 37°C, the media were removed and 150 µl/well of MTT solvent (either absolute DMSO or isopropanol containing 4 μM HCl and 0.1% Nonidet-40) was added to dissolve the formazan.
S2192	Sapitinib (AZD8931) Sapitinib (AZD8931)是一种可逆的，ATP竞争性EGFR，ErbB2和ErbB3抑制剂，无细胞试验中IC50分别为4 nM，3 nM和4 nM，作用于NSCLC细胞比Gefitinib或Lapatinib更有效，作用于ErbB家族比作用于MNK1和Flt选择性强100倍。Phase 2。	Gut, 2015, 10.1136/gutjnl-2014-309026 Clin Cancer Res, 2014, 20(17):4559-73 Clin Cancer Res, 2015, 10.1158/1078-0432.CCR-14-2701	Western blot analysis confirm suppression of the biomarker p-EGFR upon treatment with EGFR TKIs in U-CH1 and UM-Chor1. Cells were serum-starved overnight before they were treated with a range of concentrations of the EGFR inhibitors for 4 h and then EGF-spiked (50 ng/ml) for 15 min. Endogenous controls (non-serum-starved, non-EGF-spiked), untreated controls (serum-starved, non-EGF-spiked) and vehicle controls (serum-starved, treated with 2.5% DMSO, EGF-spiked) were included. Phospho-EGFR was measured by western blot.
S1194	CUDC-101 CUDC-101是一种有效的，多靶点抑制剂，作用于HDAC，EGFR和HER2，IC50分别为4.4 nM， 2.4 nM，和15.7 nM，且抑制I/II型HDACs，但是对III型， Sir-type HDACs没有抑制作用。Phase 1。	J Chem Inf Model, 2014, 54(3):881-93 ACS Med Chem Lett, 2013, 4(9):858-62 Bioorg Med Chem, 2015, 10.1016/j.bmc.2014.12.066	(a) Decay-corrected microPET/CT scan of MDA-MB-231 tumor bearing mice (n = 4) at 2, 4, and 24 h after i.v. injection of [64Cu]7. The image obtained with coinjection of CUDC-101 (20 mg/kg body weight) is shown for a 24 h blockade. Tumors are indicated by arrows. (b) Decay-corrected region-of interest (ROI) analysis on microPET images of the tumor uptake of [64Cu]7 with or without coinjection of CUDC-101 (20 mg/kg body weight). , P < 0.05; *, P < 0.01.
S2216	Mubritinib (TAK 165) Mubritinib (TAK 165)是一种有效的HER2/ErbB2抑制剂，在BT-474细胞中IC50为6 nM；而在BT-474细胞系中对EGFR，FGFR，PDGFR，JAK1，Src和Blk没有抑制作用。Phase 1。	Br J Pharmacol, 2012, 166(3):858-76 Cell Death Dis, 2013, 4:e810 Cellular Signalling, 2016, 19;28(6):652-662	(d,e) HL60 and NB4 cell flow cytometric cycle proportion assay. The cells were treated with the indicated concentrations of TAK165 for 3 days. (f) A western blot analysis of c-myc, p21 and p27 protein in HL60 and NB4 cells. The cells were treated with the indicated concentrations of TAK165 for 3 days.
S1056	AC480 (BMS-599626) AC480 (BMS-599626)是一种选择性的，高效效的HER1和HER2抑制剂，IC50分别为20 nM和30 nM。比对HER4效果强8倍左右，而比对VEGFR2， c-Kit， Lck， MET等的作用强100倍以上。Phase 1。	Cancer Cell, 2012, 22(5):656-67 J Cell Mol Med, 2013, 17(5):648-56 Asian J Androl, 2016, 10.4103/1008-682X	RCH-ACV cells were treated with ponatinib(50 nM), PCI-32765(50 nM), or BMS-599626(500 nM) over a time course, and whole-cell extracts were subjected to immunoblot analysis for total or phospho-AKT.
S1486	AEE788 (NVP-AEE788) AEE788 (NVP-AEE788)是一种有效的EGFR和HER2/ErbB2抑制剂，IC50分别为2 nM和6 nM，对VEGFR2/KDR， c-Abl， c-Src，和Flt-1作用效果稍弱，对Ins-R， IGF-1R， PKCα和CDK1没有抑制作用。Phase 1/2。	Prostate, 2013, 73(13):1453-61 PLoS One, 2015, 10(4):e0123623 Int J Clin Exp Pathol, 2013, 6(10):2082-91	EGFR-SGLT1 interaction is irresponsive to modulators of EGFR’s tyrosine kinase. A: Immunoprecipitation coupled Western blot analysis ofinteractionsbetween EGFR-HA and SGLT1-FlaginHEK293 cells treatedwith EGF or AEE788. EGFR, total EGFR; pEGFR, phosphorylated EGFR; IP, immunoprecipitation; IB, immunoblot. Input, expression levels of indicated exogenous proteinsin HEK293 whole celllysates used for the IP.
S2752	HER2-Inhibitor-1 HER2-Inhibitor-1是ARRY-380的类似物。ARRY-380是一种有效的，选择性的HER2抑制剂，IC50为8 nM，等效作用于截短的p95-HER2，作用于HER2比作用于EGFR选择性高500倍。		confluent 10cm plates, 24hour FBS starvation, then treatment with compounds at 10nM for 30mins, followed by 5 minutes of 0.05ug/ml of EGF. Pellet was sonicated (setting 5, 5 seconds, twice), then quenched with 2XGSB. Loaded 10ul on AnyKD BioRad gel (20mins at 250V), transfered with BioRad Turbo system for 15 minutes (1.5A, 25V). Blocked with 5% milk for 1 hour at RT. Rocked overnight at 1:1000 in 5% BSA with primary Abs; Anti-rabbit secondary Ab at 1:2000 in 5% milk for 1 hour, developed with Thermo Femto Kit.
S2784	TAK-285 TAK-285是一种新型，HER2和EGFR(HER1)双重抑制剂，IC50分别为17 nM和23 nM，作用于HER1/2比作用于HER4选择性高10倍以上，对MEK1/5， c-Met， Aurora B， Lck， CSK等作用效果稍弱。Phase 1。
S2816	Tyrphostin AG 879 Tyrphostin AG 879有效抑制HER2/ErbB2，IC50为1 μM，作用于ErbB2比作用于PDGFR和EGFR选择性高100到500倍。	Br J Pharmacol, 2015, 10.1111/bph.13127	Identification of tyrphostin AG879 as a Kv4.2 channel inhibitor. (A) Chemical structure of AG879. (B) Effect of AG879 on Kv4.2 channels in CHO-K1 cells. AG879 10 μM reduced the Kv4.2-mediated peak current by 31.27 ± 2.4%. The Kv4.2 channel currents were recorded by a depolarization to +40 mV for 300 ms from a holding potential −80 mV. (C) Inhibition by AG879 3, 10 and 20 μM of Kv4.2/KChIP2 co-expressed channels. (D) Concentration-dependent inhibition by AG879 of Kv4.2/KChIP2 channel shown by measuring peak and integral currents. Concentration–response curves for AG879 were fitted to the Hill equation. (E) Reversible inhibition of Kv4.2 by AG879. Maximal inhibition occurred ∼5 min after drug application. (F) Concentration-dependent inhibition by AG879 of Kv4.3 channels.
S8362	Irbinitinib (ARRY-380, ONT-380) ARRY-380 (ONT-380)是一种具有口服活性、可逆的、ATP竞争性的的ErbB2（HER2）小分子抑制剂。在细胞实验中，ARRY-380对ErbB-2和p95 HER2的IC50s分别为8 nM和7 nM，对HER2的选择性是对EGFR的500倍。具有潜在的抗肿瘤活性。	Front Oncol, 2018, 8:425 Mol Biol Cell, 2015, 26(18):3165-77
S2250	(-)-Epigallocatechin Gallate (-)-Epigallocatechin Gallate是从绿茶中分离的一种有效的抗氧化剂Polyphenol flavonoid。抑制telomerase和DNA methyltransferase，阻滞EGF受体和HER-2受体的激活，抑制脂肪酸合成酶以及谷氨酸脱氢酶的活性。	J Nutr Biochem, 2013, 24(11):1953-62 J Cell Mol Med, 2017, 10.1111/jcmm.13169 PLoS One, 2013, 8(8): e69519	(a) Huh7 cells were incubated with HCVcc of JFH-1 for 2 h before overlaying with 1% agarose dissolved in culture medium or with AR3A anti-E2 neutralizing antibodies, in the presence of 20 μg/ml SZA. EGCG (50 μM) was introduced as a positive control. At 48 h post-infection, infected cells were quantified by IF. Nuclei were stained with DAPI. (b) Numbers of cells per positive colony were determined in 15 foci.
S7810	Afatinib (BIBW2992) Dimaleate Afatinib (BIBW2992) Dimaleate 不可逆地抑制 EGFR/HER2，包括 EGFR(wt)，EGFR(L858R)，EGFR(L858R/T790M) 和 HER2，IC50 分别为0.5 nM，0.4 nM，10 nM 和 14 nM；活性比对Gefitinib抵抗型L858R-T790M EGFR突变体高100倍。	Cancer Discov, 2017, 7(6):575-585 Cancer Discov, 2013, 3(2):168-81 Gut, 2015, 10.1136/gutjnl-2014-309026	(F) Stably transduced MCF10A cells were treated with the indicated drugs at 100 nM for 4 h in EGF- and serum-free media. Cell lysates were subjected to immunoblot analyses with the indicated antibodies.
S7358	Poziotinib (HM781-36B) Poziotinib (HM781-36B)是一种不可逆的泛-HER抑制剂，对HER1，HER2，和HER4的IC50分别为3.2 nM，5.3 nM和23.5 nM。

研究领域

产品类型

HER2

信号通路图

研究领域