Crizotinib (PF-02341066)

Pfizer辉瑞授权 目录号:S1068

Crizotinib (PF-02341066) Chemical Structure

Molecular Weight(MW): 450.34

Crizotinib (PF-02341066)是一种有效的c-MetALK抑制剂,在细胞试验中IC50分别为11 nM 和 24 nM。

规格 价格 库存 购买数量  
RMB 1812.55 现货
RMB 900.49 现货
RMB 1372.81 现货
RMB 4681.47 现货
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客户购买Selleck的此次产品后发表的文献73篇:

客户使用该产品的13个实验数据:

  • (c) Western blot analyses of p-Akt (Ser473) and p-S6RP (Ser235 and Ser236) in two RCT-E565 transplanted tumors treated with vehicle or PF02341066. Samples were isolated 4 h after the last dose from mice treated with PF02341066 for 3 d. (d) Responses of RCT-E565 transplanted tumors in athymic mice to PF02341066 or vehicle. Data are means ±s.e.m. (each group, n = 6). *P < 0.005, **P < 0.001 (Student,s t test).

    Nat Med 2011 17, 1116-1120. Crizotinib (PF-02341066) purchased from Selleck.

    Ba/F3 cells grown in the presence of IL-3, or Ba/F3 cells expressing native EML4-ALK (clone #2, #10, #101, and #155) and EML4-ALK L1196M (clone #216, #302, #303, and #355), were treated with CH5424802 or PF-02341066 for 48 hr, and then the viable cells were measured by the Cell Titer-Glo Luminescent Cell Viability Assay. IC50 values were determined by plotting the drug concentration versus percentage of cell growth inhibition. Data are shown as mean ±SD (n = 3).

     

     

    Cancer Cell 2011 19, 679–690. Crizotinib (PF-02341066) purchased from Selleck.

  • Mice bearing Ba/F3-EML4-ALK (clone #10) and EML4-ALK L1196M (clone #303) were administered vehicle, CH5424802 (60 mg/kg), or PF-02341066 (100 mg/kg) orally once daily for 8 days. Tumor volume for each dose group was measured. Data are shown as mean ± SD (n = 5). Parametric Dunnett’s test: ***p < 0.001; N.S., not significant, versus vehicle treatment at final day. For pharmacodynamic assay, mice bearing Ba/F3-EML4-ALK (clone #10) and -EML4-ALK L1196M (clone #303) were orally administered at single dose of vehicle, CH5424802 (60 mg/kg), or PF-02341066 (100 mg/kg), and the tumors were collected and lysed at 4 hr post-dosing. STAT3 and phosphorylated STAT3 (Tyr 705) were detected by immunoblot analysis using antibodies against each of them (n = 2 per group).

     

     

    Cancer Cell 2011 19, 679–690. Crizotinib (PF-02341066) purchased from Selleck.

    (A) Immunoblots of MPM cells treated with the indicated concentrations of crizotinib alone for 24 h with HGF stimulation.

    Sci Rep, 2016, 6:32992. Crizotinib (PF-02341066) purchased from Selleck.

  • Three MET amplified (Hs746t, SNU-5 and MKN45) and two non-amplified cell lines (MKN74 and NUGC-4) were incubated with or without 100nM crizotinib 24 hours, and total protein was extracted using RIPA lysis buffer. Total lysates were then analyzed by immunoblotting using anti-phospho-MET, anti-total-MET, and β-actin antibodies.

    Oncotarget, 2017, 8(31):51675-51687. Crizotinib (PF-02341066) purchased from Selleck.

    Viability of Ba/F3 cells stably expressing DCTN1-ALK or EML4-ALK cDNAs after treatment with crizotinib (C). Ba/F3 cells transduced with lentiviral cDNA or empty vector were subjected to the assay, and the number of cells was counted at 72 hours.

    Oncologist, 2017, 22(2):158-164. Crizotinib (PF-02341066) purchased from Selleck.

  • Combination of EGCG with c-MET inhibitor has enhanced inhibitory effects on the growth of OS cells. MG-63 and U-2OS cells were treated with crizotinib (0.05 mM) and/or EGCG (0.08 g/L) for 48 h, and the effects on cell apoptosis (b) were determined using flow cytometry. *P<0.05 versus the control; #P<0.05 versus crizotinib-treated groups or EGCG-treated groups

    Tumour Biol, 2016, 37(4):4373-82. Crizotinib (PF-02341066) purchased from Selleck.

    (A) VimPro-Fluc activity in spheroids after 72-h treatment with control modulators of epithelial-mesenchymal transition (EMT) normalized to spheroid viability and compared to vimentin protein expression using Western blot analysis. (B) Dose-response curves for both U0126 and axitinib control modulators of EMT. RLU, relative luminescence units.

    J Biomol Screen 2011 16, 141-154. Crizotinib (PF-02341066) purchased from Selleck.

  • Secondary assay development. The invasive potential of MDA-MB-231 spheroids was measured using modified Boyden chambers coated with Matrigel™. Invading cells were fixed, stained with DAPI, and quantified by fluorescence microscopy using 5 random fields per filter insert in triplicate. U0126, PF2341066, axitinib, and PKC412 inhibited the invasive potential of MDA-MB-231 spheroids by ~90% as compared to untreated spheroids (UT). ***p ≤ 0.001. IGF1R and dasatinib displayed no statistical difference as compared to UT MDA-MB-231 spheroids.

    J Biomol Screen 2011 16, 141-154. Crizotinib (PF-02341066) purchased from Selleck.

    Crizotinib impaired tumor vascularization. a-e Representative photomicrographs (40×) of CD31 staining in negative control and indicated LFD, HFD, vehicle (veh) and crizotinib (criz) treated groups. b CD31 was quantified on 5–6 randomly selected regions of n = 2 sections each from each mouse. N = 9–10 mice (a vs b, Veh vs Criz, P = 0.0138)

    Springerplus, 2016, 5:348. Crizotinib (PF-02341066) purchased from Selleck.

  • Inhibition of signaling pathway activation in lung tumor cell lines by kinase inhibitors. Lung tumor cells were cultured in 10% FBS until reaching ∼80% confluence and then the cells were starved in serum-free medium for overnight, followed by 4-hour treatment with the inhibitors. Cell lysates were then prepared and used for determination of the pathway activation signals by the CEER assay.

    Int J Proteomics 2011 2011, 215496. Crizotinib (PF-02341066) purchased from Selleck.

    Inhibition of anchorage-independent growth of lung tumor cell lines by selected inhibitors. Each selected cell line was treated with the indicated inhibitor at 0.1 μM and 1 μM concentrations for two weeks and cell colony size formation was scored under the Nikon inverted-phase microscope.

    Int J Proteomics 2011 2011, Article ID 215496. Crizotinib (PF-02341066) purchased from Selleck.

  • Western blot analysis of c-Met, MAPK and Akt. 0-100nM PF2341066 was added.

     

     

    Dr. Zhang of Tianjin Medical University. Crizotinib (PF-02341066) purchased from Selleck.

产品安全说明书

c-Met抑制剂选择性比较

生物活性

产品描述 Crizotinib (PF-02341066)是一种有效的c-MetALK抑制剂,在细胞试验中IC50分别为11 nM 和 24 nM。
靶点
c-Met [1]
(A549, MDA-MB-231, GTL-16, HT29, 786-O, Colo-205, A498 cells)
ALK [1]
(Karpas299 cells)
11 nM 24 nM
体外研究

PF-2341066作用于mIMCD3小鼠和MDCK犬上皮细胞,作用于c-Met磷酸化作用时具有相似效果,IC50分别为5 nM 和20 nM。PF-2341066作用于表达c-Met ATP-结合位点突变型V1092I 或H1094R或 P-环突变 M1250T 的NIH3T3 细胞,具有相似的活性,且活力增高,IC50分别为19 nM,2 nM 和15 nM,而作用于表达野生型受体的NIH3T3 细胞时,IC50为13 nM。[1] 相反, 观察到PF-2341066作用于表达c-Met活化环突变型Y1230C 和Y1235D的细胞时,与作用于野生型受体相比,效果发生显著改变,IC50分别为127 nM 和92 nM。PF-2341066 作用于分别表达内源性c-Met 突变体R988C和 T1010I 的NCI-H69 和HOP92 细胞,也有效抑制c-Met 磷酸化, IC50分别为13 nM 和16 nM。与作用于c-Met相比,PF-2341066作用于VEGFR2 和PDGFRβ RTKs, 选择性高1000多倍,作用于IRK和Lck选择性高250多倍,作用于Tie2, TrkA,和TrkB选择性高40到60倍。PF-2341066 作用于RON和 Axl RTKs时选择性为20到30倍。相反,PF-2341066 作用于表达ALK RTK 的核磷蛋白 (NPM)- 间变性淋巴瘤激酶(ALK) 致癌融合突变体和 KARPAS299人间变性大细胞淋巴瘤(ALCL)细胞系时具有相近的IC50值,为24 nM。PF-2341066抑制c-Met依赖的癌细胞的肿瘤表现型,和内皮细胞的血管生成表现型。PF-2341066抑制人GTL-16胃癌细胞生长,IC50为9.7 nM。PF-2341066诱导 GTL-16细胞凋亡,IC50 为8.4 nM。PF-2341066 抑制HGF刺激的人NCI-H441肺癌细胞迁移和入侵,IC50分别为11 nM 和6.1 nM。PF-2341066抑制 MDCK细胞散射,IC50为16 nM。PF-2341066 抑制HGF-刺激的c-Met磷酸化,细胞存活,和Matrigel入侵,IC50分别为11 nM, 14 nM和35 nM。此外, PF-2341066抑制纤维蛋白胶中的血清刺激的 HMVEC分支小管形成 (形成血管)。[1] PF-2341066 作用于Karpas299 或SU-DHL-1 ALCL细胞,也有效抑制 NPM-ALK磷酸化,IC50 为24 nM。PF-2341066 有效抑制细胞增殖,伴随着使细胞周期停在G(1)-S期,且诱导 ALK阳性的 ALCL 细胞凋亡,IC50为30 nM, 但是作用于ALK阴性的淋巴瘤细胞则无效果。 [2] 此外, PF-2341066 抑制骨肉瘤的一些活动行为,及其肿瘤生长 (例如,增殖和存活)和转移 (例如,入侵和形成克隆)。[3]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
BAF3 M375TmN6fG:2b4jpZ{BCe3OjeR?= MXq0PEBp M1PO[WROW09? Mn21R5l1d3SxeHnjbZR6KGGpYXnud5QhdW:3c3WgRmFHOyClZXzsd{BmgHC{ZYPzbY5oKEGOSzDGNVE4PExibYX0ZY51KGOxZYjwdoV{e2mwZzDFUWw1KHerdHigTWM2OCCxZjCwMlYzKM7:TR?= NEK3S4czOTV5MkW4PS=>
BAF3 MkfBR5l1d3SxeHnjJGF{e2G7 M17JRlQ5KGh? MVjEUXNQ NHO4OnZEgXSxdH;4bYNqfHliYXfhbY5{fCCvb4Xz[UBDSUZ|IHPlcIx{KGW6cILld5NqdmdiQVzLJGwyOTl4TTDteZRidnRiY3;lfJBz\XO|aX7nJGVOVDRid3n0bEBKSzVyIH;mJFIvOiEQvF2= NGDLXIozOTV5MkW4PS=>
BAF3 NIfUPVdEgXSxdH;4bYMhSXO|YYm= MXi0PEBp MnHTSG1UVw>? NXTpXlNlS3m2b4TvfIlkcXS7IHHnZYlve3RibX;1d4UhSkGIMzDj[YxteyCneIDy[ZN{cW6pIFXNUFQuSUyNIIfpeIghUUN3MDDv[kAxNjJ6IN88US=> MoTNNlE2PzJ3OEm=
Kelly NFXDXJlEgXSxdH;4bYMhSXO|YYm= NH3UbG1FVVOR NITaTHBEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBM\WyueTDj[YxteyCneIDy[ZN{cW6pIFHMT{BHOTF5NFygcZV1[W62IIfpeIghUUN3MDDv[kAxNjR{IN88US=> NETTdlEzOTV5MkW4PS=>
SH-SY5Y M3THfWN6fG:2b4jpZ{BCe3OjeR?= NEDtTmlFVVOR Mlf3R5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gV2guW1l3WTDj[YxteyCneIDy[ZN{cW6pIFHMT{BHOTF5NFygcZV1[W62IIfpeIghUUN3MDDv[kAxNjV|IN88US=> M4\QVFIyPTd{NUi5
SMS-KCN MlLGR5l1d3SxeHnjJGF{e2G7 NVHwOmJ2TE2VTx?= Mm\ZR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gV21UNUuFTjDj[YxteyCneIDy[ZN{cW6pIFHMT{BTOTJ5NWGgcZV1[W62IIfpeIghUUN3MDDv[kAxNjlzIN88US=> MWOyNVU4OjV6OR?=
BAF3 NH;yRpNEgXSxdH;4bYMhSXO|YYm= MX20PEBp MnvrSG1UVw>? NWLJNlFVS3m2b4TvfIlkcXS7IHHnZYlve3RibX;1d4UhSkGIMzDj[YxteyCneIDy[ZN{cW6pIGTlcE1CVEtid3n0bEBKSzVyIH;mJFAvOTlizszN MX2yNVU4OjV6OR?=
3T3 NFvBTGFHfW6ldHnvckBCe3OjeR?= MVqxJIg> Mm\xSG1UVw>? MmDDTY5pcWKrdHnvckBw\iCUT16gZZN{\XO|ZXSgZZMh\3Kxd4ToJIZi[3Sxcj3pcoR2[2WmIHH1eI9xcG:|cHjvdplt[XSrb36ge4l1cCCLQ{WwJI9nKDBwMEig{txO NV[5VnV5OjF6MUK0NVQ>
3T3-E MoToSpVv[3Srb36gRZN{[Xl? MXOxJIg> MmDWSG1UVw>? NHzFZ4JKdmirYnn0bY9vKG:oIGTJSVIh[XO|ZYPz[YQh\3Kxd4ToJIZi[3Sxcj3pcoR2[2WmIHH1eI9xcG:|cHjvdplt[XSrb36ge4l1cCCLQ{WwJI9nKDBwNES4JO69VQ>? MUmyNVgyOjRzNB?=
A549 NVi3dIVTU2mwYYPlJGF{e2G7 NIHrNWgyKGh? NEHrR5BFVVOR NGTWNIlKdmirYnn0bY9vKG:oIHj1cYFvKHKnY3;tZolv[W62IHOtUWVVKGurbnHz[UBmgHC{ZYPz[YQh[XO|ZYPz[YQh[XNiaX7obYJqfGmxbjDv[kBJT0ZvaX7keYNm\CCjdYTvdIhwe3Cqb4L5cIF1cW:wIIfpeIghUUN3MDDv[kAxNjByODFOwG0> Mlr3NlE5OTJ2MUS=
BAF3-BCL M4O3PGZ2dmO2aX;uJGF{e2G7 MkDDNUBp NVv0W2t{TE2VTx?= MnzoTY5pcWKrdHnvckBw\iCDQlygZZN{\XO|ZXSgZZMh\3Kxd4ToJIZi[3Sxcj3pcoR2[2WmIHH1eI9xcG:|cHjvdplt[XSrb36ge4l1cCCLQ{WwJI9nKDFwMUW5JO69VQ>? M1nRZVIyQDF{NEG0
HEK293 NXLic|ZqTnWwY4Tpc44hSXO|YYm= Mn;6NUBp Ml;SSG1UVw>? NXrnOWpbUW6qaXLpeIlwdiCxZjDBXGwh[XO|ZYPz[YQh[XNiZ4Lve5RpKG[jY4Tvdk1qdmS3Y3XkJIF2fG:yaH;zdIhwenmuYYTpc44hf2m2aDDJR|UxKG:oIECuNlk1KM7:TR?= NFfpTnEzOThzMkSxOC=>
HEK293 Mn;BSpVv[3Srb36gRZN{[Xl? M1jCW|EhcA>? MVfEUXNQ MUDJcohq[mm2aX;uJI9nKEmUIHHzd4V{e2WmIHHzJIdzd3e2aDDmZYN1d3JvaX7keYNm\CCjdYTvdIhwe3Cqb4L5cIF1cW:wIIfpeIghUUN3MDDv[kAzNjh6NzFOwG0> NE\4VlIzOThzMkSxOC=>
Jurkat NEGx[ohHfW6ldHnvckBCe3OjeR?= MkTENUBp MVTEUXNQ NV7obWdEUW6qaXLpeIlwdiCxZjDMR2sh[XO|ZYPz[YQh[XNiZ4Lve5RpKG[jY4Tvdk1qdmS3Y3XkJIF2fG:yaH;zdIhwenmuYYTpc44hf2m2aDDJR|UxKG:oIEKuO|QyKM7:TR?= NUT1T405OjF6MUK0NVQ>
KARPAS299 NIfKcmdMcW6jc3WgRZN{[Xl? MV:xJIg> M1PmUGROW09? M2Lz[mlvcGmkaYTpc44hd2ZiQVzLJIF{e2W|c3XkJIF{KGe{b4f0bEBn[WO2b4KtbY5lfWOnZDDheZRweGixc4Doc5J6dGG2aX;uJJdqfGhiSVO1NEBw\iByLkCyJO69VQ>? M1XLclIyQDF{NEG0
PAE NETHe3pHfW6ldHnvckBCe3OjeR?= MVuxJIg> NEKxRmVFVVOR MnfsTY5pcWKrdHnvckBw\iCWUlvCJIF{e2W|c3XkJIF{KGe{b4f0bEBn[WO2b4KtbY5lfWOnZDDheZRweGixc4Doc5J6dGG2aX;uJJdqfGhiSVO1NEBw\iByLkO5PUDPxE1? M{DPfVIyQDF{NEG0
BAF3 MonESpVv[3Srb36gRZN{[Xl? MlXRNk0{KGR? M4HmOGROW09? NV3qdZBSUW6qaXLpeIlwdiCxZjDUSWwu\nW|ZXSgbY5{fWyrbjDy[YNmeHSxcjDlfJBz\XO|ZXSge4l1cCCLQ{WwJI9nKDFwNkSzJO69VQ>? M3;Q[VI{PzR{MkWy
KARPAS299 M{TYfGN6fG:2b4jpZ{BCe3OjeR?= NFjNNXYzNTNiZB?= NYDvN2dsTE2VTx?= M1zuOGlEPTB;MD6wOlQzKM7:TR?= MVmyN|c1OjJ3Mh?=
EBC1 MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVS3NkBp M4\jPWROW09? MnT6TWM2OD1yLkCyN{DPxE1? M4jWXlI{QTl|M{K4
HCT116 NF;MeolIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4DKcVczKGh? NH7oe21FVVOR NUX1WYZOUUN3ME2xOE45OiEQvF2= Mo\oNlM6QTN|Mki=
MCF7 MVfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHX4ZVQ4OiCq MmG4SG1UVw>? NHLGd|ZKSzVyPUmuOVgh|ryP NYTxbJJtOjN7OUOzNlg>
MDA-MB-231 NWPMTlNGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mn\wO|IhcA>? MnXDSG1UVw>? NU\0XVhbUUN3ME2xNE45KM7:TR?= NUe1b5NpOjN7OUOzNlg>
MKN45 NYrrUpU2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXnPN|J{PzJiaB?= NYPU[3piTE2VTx?= NILKb5VKSzVyPUCuNFE{KM7:TR?= NUHtNZNyOjN7OUOzNlg>
NCI-H441 M1mwTWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVi3NkBp NFHxeJRFVVOR M{CxOWlEPTB;MUeuNlUh|ryP NHzwSZIzOzl7M{OyPC=>
NCI-H661 Mm\KS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXS3NkBp M{HQRWROW09? MkLLTWM2OD1zMT60O{DPxE1? NFTGb4YzOzl7M{OyPC=>
SK-MEL-28 NILMUGJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXrsZoFCPzJiaB?= NYXLcmNGTE2VTx?= MYnJR|UxRTFyLkm3JO69VQ>? NXLT[lRFOjN7OUOzNlg>
SKOV3 NF\vN25Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYe3NkBp M3fqW2ROW09? M3rLRmlEPTB;MUKuPFUh|ryP NUPRUo1ZOjN7OUOzNlg>
SNU5 NWrWVYY2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVe3NkBp MWnEUXNQ NH\zW3NKSzVyPUCuNFE3KM7:TR?= MVuyN|k6OzN{OB?=
NCI-H2228 NF33TYVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MV23NkBp NIf6e5NFVVOR NWqxfFJkUW6qaXLpeIlwdiCxZjDBUGsu\nW|aX;uJIRzcX[nbjDj[YxtKHC{b3zp[oVz[XSrb36ge4l1cCCLQ{WwJI9nKDBwMUG4JO69VQ>? MUKyOFQ{OjlyOR?=
NCI-H3122 NEjPNlNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1;SPVczKGh? M33DZmROW09? MW\Jcohq[mm2aX;uJI9nKEGOSz3meZNqd25iZILpeoVvKGOnbHygdJJwdGmoZYLheIlwdiC5aYToJGlEPTBib3[gNE4yODhizszN MnfkNlQ1OzJ7MEm=
NCI-H3122 NX\VeGZDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlLuO|IhcA>? NITsS2hFVVOR NFnpfVNKdmirYnn0bY9vKG:oIFHMT{1nfXOrb36g[JJqfmWwIHPlcIwheHKxbHnm[ZJifGmxbjDpckBpfW2jbjDOR2kuUDNzMkKgZ4VtdHNiaHHyZo9zcW6pIFHMT{BIOTJ4OVGgcZV1[W62IIfpeIghUUN3MDDv[kAxNjZ{MzFOwG0> M4fBc|I1PDN{OUC5
NCI-H3122 Ml\mS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUTJPZVYPzJiaB?= M{LEXWROW09? NVHPSFNTUW6qaXLpeIlwdiCxZjDBUGsu\nW|aX;uJIRzcX[nbjDj[YxtKHC{b3zp[oVz[XSrb36gbY4hcHWvYX6gUmNKNUh|MUKyJINmdGy|IHjhdoJwemmwZzDBUGshVDFzOU\NJI12fGGwdDD3bZRpKEmFNUCgc4YhOC56M{ig{txO NVv2PGtSOjR2M{K5NFk>
NIH-3T3 NWTUR|BiU2mwYYPlJGF{e2G7 MVSxJIg> NYfrfphOTE2VTx?= MVXJcohq[mm2aX;uJI9nKGi3bXHuJJdqdGRidInw[UBGVUx2LX\1d4VlKEGOSzDlfJBz\XO|ZXSgZZN{\XO|ZXSgZZMheGixc4Doc5J6dGG2ZXSgRWxMKGyndnXsJJdqfGhiSVO1NEBw\iByLkC4JO69VQ>? MlP5NlQ1OzJ7MEm=
NIH-3T3 NY\yOJhyU2mwYYPlJGF{e2G7 NF[xTmIyKGh? MX7EUXNQ MUTJcohq[mm2aX;uJI9nKGi3bXHuJGVOVDRvZoXz[YQhSUyNIFexNlY6SSCvdYThcpQh\XiycnXzd4VlKGG|c3Xzd4VlKGG|IIDoc5NxcG9vQVzLJIxmfmWuIIfpeIghUUN3MDDv[kAxNjZyNTFOwG0> NEPjc5AzPDR|MkmwPS=>
NIH-3T3 NWi0b3ljU2mwYYPlJGF{e2G7 MYmxJIg> NFnJRZhFVVOR M1jP[mlvcGmkaYTpc44hd2ZiaIXtZY4hTU2OND3meZNm\CCDTFugV|EzOD[\IH31eIFvfCCneIDy[ZN{\WRiYYPz[ZN{\WRiYYOgdIhwe3Cqbz3BUGshdGW4ZXyge4l1cCCLQ{WwJI9nKDBwNkK2JO69VQ>? NVn0RWRWOjR2M{K5NFk>
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NCI-H748 M330WGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYXJR|UxRTJ4LkWxN|ch|ryP M1XRdXNCVkeHUh?=
PF-382 NWXyXYRQT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1f4NGlEPTB;MkeuNlIzOyEQvF2= NFnqU2RUSU6JRWK=
ATN-1 M3u5W2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NX;hN5Q1UUN3ME2yO{4{PzN{IN88US=> M3jFXnNCVkeHUh?=
L-540 NEnZVI9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFflToVKSzVyPUK3MlY1PTlizszN MVrTRW5ITVJ?
LXF-289 NXrmTG5iT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mkm2TWM2OD1{Nz63OVE6KM7:TR?= M{XBcXNCVkeHUh?=
LS-513 NXLVSHZrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NX;yUIZuUUN3ME2yPE4yQDB5IN88US=> NXfrc5hrW0GQR1XS
NCI-H1581 MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3rRUGlEPTB;M{CuN|k4PiEQvF2= NYrFd29JW0GQR1XS
ES6 NHfjPFlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoeyTWM2OD1|MD62PFk6KM7:TR?= NWDSeW43W0GQR1XS
SW982 M4rFU2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGDa[ZRKSzVyPUOwMlg2PjZizszN MnHLV2FPT0WU
DOHH-2 NULXc4NzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2\hOWlEPTB;M{GuOVg6OyEQvF2= NGjnPYNUSU6JRWK=
DB MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NY\he4lMUUN3ME2zN{46PDNzIN88US=> MknJV2FPT0WU
MPP-89 NFLJZVJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NV\Gb5Z2UUN3ME2zOE4yPzV4IN88US=> MV3TRW5ITVJ?
LB831-BLC MmnvS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVHJR|UxRTN2LkWxPFQh|ryP MnTUV2FPT0WU
NB5 NYXHeoxTT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXPa[Hg2UUN3ME2zOE45PTN3IN88US=> MlXTV2FPT0WU
GB-1 MWDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHziOGtKSzVyPUO1MlA1PjlizszN M1Tnc3NCVkeHUh?=
TE-15 M1TkZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWXZTphjUUN3ME2zOU4zOjN6IN88US=> M1;QNXNCVkeHUh?=
LC4-1 NWrZPHJFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUToe4pIUUN3ME2zOU4{QDR5IN88US=> MUTTRW5ITVJ?
NCI-H747 MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUDJR|UxRTN4LkGzOlkh|ryP M4X1U3NCVkeHUh?=
NTERA-S-cl-D1 NWXwR5lHT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1r3[mlEPTB;M{iuO|M1PyEQvF2= MkL3V2FPT0WU
SK-MM-2 NEfpUZJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NH;IZWRKSzVyPUSwMlEyPDZizszN M2rJV3NCVkeHUh?=
TGW Mm\wS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUTuN3pCUUN3ME20NU4xPTZ|IN88US=> M33xS3NCVkeHUh?=
ONS-76 MmTQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlPDTWM2OD12Mj60PFg{KM7:TR?= Ml3FV2FPT0WU
CPC-N NYD1R4tMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NET4bY5KSzVyPUSyMlk6PzFizszN NX30Oo8zW0GQR1XS
ES4 NHLyfI5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlLITWM2OD12ND60NVU{KM7:TR?= NUXHOIg{W0GQR1XS
Daudi NWjmb5VWT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3zLW2lEPTB;NEWuNFgzPyEQvF2= M2qxVHNCVkeHUh?=
MOLT-4 M1;IeWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NF2zelZKSzVyPUS1MlA5PTNizszN Mn\EV2FPT0WU
HT-144 MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYXJR|UxRTR4LkeyOkDPxE1? NWL2PJN2W0GQR1XS
SW872 MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWL3c4NoUUN3ME20PE4yQTN|IN88US=> M2LEd3NCVkeHUh?=
D-283MED Ml7CS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVnydWZNUUN3ME20PE4{PTR{IN88US=> M1zScXNCVkeHUh?=
NCI-H2126 MoPFS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmPkTWM2OD12OD64OFc3KM7:TR?= MWHTRW5ITVJ?
NCI-SNU-16 NInrXppIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXjJR|UxRTR7LkKxOFMh|ryP MUjTRW5ITVJ?
CESS NYS1cW95T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXT6dnF4UUN3ME20PU42ODh6IN88US=> NIrUN4FUSU6JRWK=
A101D MmDzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmTPTWM2OD12OT65O|M3KM7:TR?= MnTHV2FPT0WU

... Click to View More Cell Line Experimental Data

体内研究 PF-2341066每天按50 mg/kg和75 mg/kg剂量处理GTL-16 模型, 引起大肿瘤 (体积大于600 mm3) 明显衰退,且按43天处理日程处理后,平均肿瘤体积降低60%。在另一项研究中, PF-2341066处理3个月以上,完全抑制GTL-16肿瘤生长,PF-2341066每天按50 mg/kg剂量处理小鼠,3个月后,只有1/12小鼠的肿瘤生长得到提高。PF-2341066每天按50 mg/kg剂量处理NCI-H441 NSCLC 模型处理周期为38天,观察到平均肿瘤体积降低43%。PF-2341066 每天按50 mg/kg剂量作用于 Caki-1 RCC模型,处理周期为33天,观察到平均肿瘤体积降低53%,且每种肿瘤体积降低至少30%。PF-2341066每天按 50 mg/kg剂量作用于 U87MG 恶性胶质瘤或PC-3前列腺癌移植瘤模型,几乎完全抑制肿瘤生长,在实验最后一天,抑制分别达97% 或84%。相反, PF-2341066每天按50 mg/kg剂量口服给药处理 MDA-MB-231 乳腺癌模型,或 DLD-1 结肠癌模型,不会显著抑制肿瘤生长。PF-2341066每天按12.5 mg/kg, 25 mg/kg, 和50 mg/kg剂量作用于 GTL-16 肿瘤,观察到CD31阳性内皮细胞显著降低,这种作用存在剂量依赖性,说明 MVD 受抑制,且具有相关的抗癌高效性,这种作用也存在剂量依赖性。PF-2341066 作用于GTL-16 和 U87MG 模型,显著降低人VEGFA 和IL-8血浆水平,这种作用存在剂量依赖性。PF-2341066口服处理GTL-16 肿瘤,观察到磷酸化的c-Met, Akt, Erk, PLCλ1,和 STAT5水平显著受抑制。[1]PF-2341066 每天按100 mg/kg剂量口服处理携带Karpas299 ALCL 移植瘤的SCID Beige 小鼠,具有抗癌高效性,这种作用存在剂量依赖性,处理15天,所有肿瘤完全衰退。此外, PF-2341066抑制关键NPM-ALK信号调节器, 包括磷脂酶C-γ, 信号转导器,及转录因子3, 细胞外信号调节激酶, 和Akt的激活剂,这些与 NPM-ALK 磷酸化和功能受抑制相关。[2] PF-2341066 抑制骨肉瘤的一些活动行为,及其肿瘤生长(例如, 增殖和存活)和转移 (例如,入侵和形成克隆)。PF-2341066口服饲喂裸鼠,抑制生长和相关的骨肉瘤裸鼠移植瘤的骨基质的形成。[3] PF-2341066 按50 mg/kg 剂量处理 c-MET-扩增的GTL-16移植瘤,引起肿瘤衰退,这与18F-FDG 摄取的缓慢降低相关,且降低葡糖糖转运蛋白 1, GLUT-1的表达。[4]

推荐的实验操作(此推荐来自于公开的文献所以Selleck并不保证其有效性)

激酶实验:

[1]

+ 展开

生化激酶实验:

使用连续耦合的分光光度测定c-Met催化活性,通过分析NADH消耗率而测定c-Met诱导的ADP产量,这种作用具有时间依赖性。在 340 nm处使用分光光度法在指定时间点测定吸光值的降低而计算NADH的消耗量。为了测定Ki值, 在含实验试剂的实验孔中加入不同浓度PF-2341066,然后在37oC下温育10分钟。加入c-Met酶开始进行实验反应。
细胞实验:

[1]

+ 展开
  • Cell lines: GTL-16胃癌细胞和T47D乳腺癌细胞
  • Concentrations: 0 nM-256 nM
  • Incubation Time: 1小时
  • Method:

    GTL-16胃癌细胞和T47D乳腺癌细胞接种在96孔板上,孔中含培养基,培养基中含10% 胎牛血清(FBS),然后转移到无血清培养基中[含0.04%牛血清蛋白(BSA)],处理 24小时。 在调查配体依赖的RTK 磷酸化实验中,加入相应的生长因子,处理20分钟。细胞和 PF-2341066和/或适当配体在指定时间温育1小时,然后使用含 1 mmol/L Na3VO4的HBSS冲洗细胞一次,然后从细胞中获得蛋白裂解物。随后,通过夹心酶联免疫吸附试验法使用特定的捕获抗体在96孔板上测定选定蛋白激酶的磷酸化,使用特点检测抗体测定磷酸化的酪氨酸残基。抗体包被的实验板(a) 在蛋白裂解物存在时,在4oC下过夜;(b)在溶于PBS的1% Tween-20 中冲洗7次;(c)在辣根过氧化物酶标记的抗总磷酸(PY-20)抗体(1:500)中温育20分钟;(d) 再次冲洗7次;(e)在3,3,5,5-四甲基联苯胺过氧化物酶底物中温育,开始显示反应,加入0.09 N H2SO4终止反应; (f)在450 nm 处使用分光光度计测定吸光度。


    (Only for Reference)
动物实验:

[1]

+ 展开
  • Animal Models: 携带NCI-H441,或DLD-1,或MDA-MB-231的雌性和雄性nu/nu小鼠
  • Formulation: --
  • Dosages: 12.5 mg/kg/day, 25 mg/kg/day, 和50 mg/kg/day
  • Administration: 口服处理
    (Only for Reference)

溶解度 (25°C)

体外 DMSO 9 mg/mL (19.98 mM)
Water Insoluble
Ethanol Insoluble
体内 从左到右依次将纯溶剂加入产品,现配现用(数据来自Selleck实验检测而非文献):
5% DMSO+30% PEG 300+dd H2O
5mg/mL

* 溶解度检测是由Selleck技术部门检测的,可能会和文献中提供的溶解度有所差异,这是由于生产工艺和批次不同产生的正常现象。请按照顺序依次加入各个纯溶剂。

化学数据

分子量 450.34
化学式

C21H22Cl2FN5O

CAS号 877399-52-5
稳定性 powder
in solvent
别名 N/A

计算器

摩尔浓度计算器

摩尔浓度计算器

本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系,公式为:

质量 (g) = 浓度 (mol/L) x 体积 (L) x 分子量 (g/mol)

摩尔浓度计算公式

  • 质量
    浓度
    体积
    分子量

*在配置溶液时,请务必参考Selleck产品标签上、MSDS / COA(可在Selleck的产品页面获得)批次特异的分子量使用本工具。

稀释计算器

稀释计算器

用本工具协助配置特定浓度的溶液,使用的计算公式为:

开始浓度 x 开始体积 = 最终浓度 x 最终体积

稀释公式

稀释公式一般简略地表示为: C1V1 = C2V2 ( 输入 输出 )

  • C1
    V1
    C2
    V2

在配置溶液时,请务必参考Selleck产品标签上、MSDS / COA(可在Selleck的产品页面获得)批次特异的分子量使用本工具。.

连续稀释计算器方程

  • 连续稀释

  • 计算结果

  • 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):
分子量计算器

分子量计算器

通过输入化合物的化学式来计算其分子量:

总分子量:g/mol

注:化学分子式大小写敏感。C10H16N2O2 c10h16n2o2

摩尔浓度计算器

质量 浓度 体积 分子量
计算

临床试验信息

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT03126916 Recruiting Childhood Ganglioneuroblastoma|Childhood Neuroblastoma|INRG Stage L2|INRG Stage M|INRG Stage MS|NMYC Gene Amplification|Recurrent Neuroblastoma Children''s Oncology Group|National Cancer Institute (NCI) May 9 2018 Phase 3
NCT01979536 Recruiting Anaplastic Large Cell Lymphoma ALK-Positive|Ann Arbor Stage II Noncutaneous Childhood Anaplastic Large Cell Lymphoma|Ann Arbor Stage III Noncutaneous Childhood Anaplastic Large Cell Lymphoma|Ann Arbor Stage IV Noncutaneous Childhood Anaplastic Large Cell Lymphoma|CD30-Positive Neoplastic Cells Present National Cancer Institute (NCI) November 8 2013 Phase 2
NCT02040870 Completed Non-Small Cell Lung Cancer Novartis Pharmaceuticals|Novartis March 7 2014 Phase 1|Phase 2
NCT01531361 Active not recruiting Advanced Malignant Neoplasm|BRAF Gene Mutation|Metastatic Malignant Neoplasm|Recurrent Malignant Neoplasm|Refractory Malignant Neoplasm M.D. Anderson Cancer Center|National Cancer Institute (NCI) February 6 2012 Phase 1
NCT02761057 Recruiting Stage III Renal Cell Cancer AJCC v7|Stage IV Renal Cell Cancer AJCC v7|Type 1 Papillary Renal Cell Carcinoma|Type 2 Papillary Renal Cell Carcinoma National Cancer Institute (NCI) April 5 2016 Phase 2
NCT02094573 Active not recruiting Carcinoma Non-Small-Cell Lung Ariad Pharmaceuticals June 4 2014 Phase 2

技术支持

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操作手册

如果有其他问题,请给我们留言。

  • * 必填项

常见问题及建议解决方法

  • 问题 1:

    Could you tell me whether this product represents the pure R-form of crizotinib, or is the the racemic Crizotinib, so a mixture of the S- and the R-form?

  • 回答:

    Our S1068 Crizotinib is R enantiomer(except batch 05 and 06, they are racemate), and S7505 is S enantiomer.

c-Met Signaling Pathway Map

c-Met Inhibitors with Unique Features

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID