Alectinib (CH5424802)

Catalog No.S2762

Alectinib (CH5424802) is a potent ALK inhibitor with IC50 of 1.9 nM in cell-free assays, sensitive to L1196M mutation and higher selectivity for ALK than PF-02341066, NVP-TAE684 and PHA-E429.

Price Stock Quantity  
USD 170 In stock
USD 270 In stock
USD 770 In stock
Bulk Inquiry

Massive Discount Available

Free Overnight Delivery on all orders over $ 500.

Alectinib (CH5424802) Chemical Structure

Alectinib (CH5424802) Chemical Structure
Molecular Weight: 482.62

Validation & Quality Control

3 customer reviews :

Quality Control & MSDS

Related Compound Libraries

Alectinib (CH5424802) is available in the following compound libraries:

ALK Inhibitors with Unique Features

  • Non-specific ALK Inhibitor

    GSK1838705A IGF-1R, IC50=2.0 nM; IR, IC50=1.6 nM, ALK, IC50=0.5 nM.

  • Most Potent ALK Inhibitor

    Ceritinib (LDK378) ALK, IC50=0.2 nM.

  • FDA-approved ALK Inhibitor

    Crizotinib (PF-02341066) Approved by FDA for non-small cell lung carcinoma (NSCLC).

  • Newest ALK Inhibitor

    ASP3026 Novel and selective inhibitor for ALK with IC50 of 3.5 nM.

Product Information

  • Compare ALK Inhibitors
    Compare ALK Products
  • Research Area
  • Inhibition Profile
  • Combination Therapy
    Combination Therapy

Product Description

Biological Activity

Description Alectinib (CH5424802) is a potent ALK inhibitor with IC50 of 1.9 nM in cell-free assays, sensitive to L1196M mutation and higher selectivity for ALK than PF-02341066, NVP-TAE684 and PHA-E429.
Targets ALK (F1174L) [1]
(Cell-free assay)
ALK [1]
(Cell-free assay)
ALK (R1275Q) [1]
(Cell-free assay)
INSR [1]
(Cell-free assay)

 View  More

IC50 1 nM 1.9 nM 3.5 nM 550 nM
In vitro The dissociation constant (KD) value of CH5424802 for ALK in an ATP-competitive manner is 2.4 nM. CH5424802 has substantial inhibitory potency against both native ALK and L1196M with Ki of 0.83 nM and 1.56 nM, respectively. CH5424802 prevents autophosphorylation of ALK in NCI-H2228 NSCLC cells expressing EML4-ALK. CH5424802 also suppresses the phosphorylation of STAT3 and AKT, but not of ERK1/2. CH5424802 completely inhibits the phosphorylation of STAT3 at Tyr705. CH5424802 is preferentially efficacious against NCI-H2228 cells expressing EML4-ALK, but not ALK fusion-negative NSCLC cell lines, including HCC827 cells (EGFR exon 19 deletion), A549 cells (KRAS mutant), or NCI-H522 cells (EGFR wild-type, KRAS wild-type, and ALK wild-type) in monolayer culture. CH5424802 elicits an apoptotic marker—caspase-3/7-like activation—in NCI-H2228 spheroid cells. CH5424802 blocks the growth of two lymphoma lines, KARPAS-299 and SR, with NPM-ALK fusion protein but does not influence the growth of an HDLM-2 lymphoma line without ALK fusion. [1] CH5424802 displays high target selectivity and the stronger anti-proliferative activity against KARPAS-299. CH5424802 inhibits KAPRAS-299 with an IC50 of 3 nM, and KDR with IC50 of 1.4 μM. The metabolic stability of CH5424802 is very high.[2]
Cell Data
Cell LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
NCI-H2228M1HoTGtqdmG|ZTDhd5NigQ>?NUHUTnpbhjFizszNM4TNSZBz\X[nboTzJIF2fG:yaH;zdIhwenmuYYTpc44hd2ZiQVzLM1jSeVIyPTd3OE[2
KARPAS-299M1vZO2dzd3e2aDDpcohq[mm2b4L5JIF{e2G7MYL+NVAh|ryPM3jhdGlEPTB;MzDuUS=>M{GwTFIyPTd3OE[2
SRMlnyS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?M4DOSp4yOCEQvF2=MWnJR|UxRTZwOTDuUS=>NIDRXFgzOTV5NUi2Oi=>
HDLM-2NVq5PVRUT3Kxd4ToJIlvcGmkaYTvdpkh[XO|YYm=M{XRbp4yOCEQvF2=NWPuO4tpUUN3ME6xNEwxODBibl2=NIjrbW8zOTV5NUi2Oi=>
NB-1MnnmS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?Mn[2glExKM7:TR?=MlPKTWM2OD12LkWgcm0>NYPDTlVmOjF3N{W4OlY>
KELLYMXnHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?Ml:zglExKM7:TR?=MV3JR|UxRTZ{IH7NMV[yNVU4PTh4Nh?=
SK-N-FIM{\0U2dzd3e2aDDpcohq[mm2b4L5JIF{e2G7MXr+NVAh|ryPNYDxZXkzUUN3ME6xNEwxODBibl2=NHLVeYozOTV5NUi2Oi=>
NCI-H2228NFHxdVFIem:5dHigbY5pcWKrdH;yfUBie3OjeR?=M2nnRp4yOCEQvF2=MnT6TWM2OD13MzDuUS=>NUXxNppDOjF3N{W4OlY>
Calu-3NHvySWdIem:5dHigbY5pcWKrdH;yfUBie3OjeR?=MVn+NVAh|ryPNUTDO4ZVUUN3ME2+NVAtODByIH7NMlr0NlE2PzV6Nk[=
PC-1NVzIR|V7T3Kxd4ToJIlvcGmkaYTvdpkh[XO|YYm=NWDudGlxhjFyIN88US=>MmjZTWM2OD5zMDywNFAhdk1?M3fPZ|IyPTd3OE[2
NCI-H23M2nnSGdzd3e2aDDpcohq[mm2b4L5JIF{e2G7NFvpSmN,OTBizszNNInmdndKSzVyPUO2NFAhdk1?MXiyNVU4PTh4Nh?=
Calu-1M3jNbWdzd3e2aDDpcohq[mm2b4L5JIF{e2G7MVL+NVAh|ryPMWDJR|UxRjFyLECwNEBvVQ>?Mn\ZNlE2PzV6Nk[=
NCI-H2009MlzJS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?Mo\ZglExKM7:TR?=NFzKTZJKSzVyPkGwMFAxOCCwTR?=MVuyNVU4PTh4Nh?=
NCI-H1993M3nHeGdzd3e2aDDpcohq[mm2b4L5JIF{e2G7MXL+NVAh|ryPNWXZSHozUUN3ME6xNEwxODBibl2=NWDLXI5FOjF3N{W4OlY>
MKN-45MUnHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?MX;+NVAh|ryPM2LYbWlEPTB-MUCsNFAxKG6PNGDWZ5AzOTV5NUi2Oi=>
SNU-5NGfMfVZIem:5dHigbY5pcWKrdH;yfUBie3OjeR?=M1LkSZ4yOCEQvF2=NHyydGJKSzVyPUG4NFAhdk1?MluzNlE2PzV6Nk[=
KATO-IIIM{TJcmdzd3e2aDDpcohq[mm2b4L5JIF{e2G7MnXsglExKM7:TR?=MknXTWM2OD15OUCwJI5ONVq0fGlOOjF3N{W4OlY>
SK-BR-3M1fTVGdzd3e2aDDpcohq[mm2b4L5JIF{e2G7M1Tz[Z4yOCEQvF2=MWPJR|UxRjFyLECwNEBvVQ>?MX:yNVU4PTh4Nh?=
BT-483MYjHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?MnjRglExKM7:TR?=NWnBWWhIUUN3ME6xNEwxODBibl2=MlLwNlE2PzV6Nk[=
PC-3NG\EfJVIem:5dHigbY5pcWKrdH;yfUBie3OjeR?=Mmj1glExKM7:TR?=NF;Xe3RKSzVyPkGwMFAxOCCwTR?=NH;m[oEzOTV5NUi2Oi=>
22Rv1MXnHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?MoPLglExKM7:TR?=MV3JR|UxRjFyLECwNEBvVQ>?MYmyNVU4PTh4Nh?=
U-87 MGM{TRUWdzd3e2aDDpcohq[mm2b4L5JIF{e2G7M1K0NJ4yOCEQvF2=MoW5TWM2OD5zMDywNFAhdk1?Mnn2NlE2PzV6Nk[=
H3122M2KxVmdzd3e2aDDpcohq[mm2b4L5JIF{e2G7NHnCSVh,OTBizszNMYTJR|UxRTN|IH7NNFXYfXUzPTB7NkSwNC=>
LC-2/adM{HIW2Fxd3C2b4Ppd{Bie3OjeR?=MV\+NUDPxE1?NGi3SIpFVVORNELadoZqdmS3Y3XzJIFxd3C2b4Ppdy=>MoiyNlU{PDl|MEe=
LC-2/adMVnGeY5kfGmxbjDhd5NigQ>?NFf5XFF,OSEQvF2=M3SyVmROW09?MVTpcohq[mm2czD0bIUhVUGSSzDzbYdv[WyrbnegdIF1cHejeR?=MWqyOVM1QTNyNx?=
Ba/F3NFzCTFJHfW6ldHnvckBie3OjeR?=Ml70glEh|ryPNX\ndnRzTE2VTx?=NUDIXGRFe3WycILld5NmeyCyaH;zdIhwenmuYYTpc44hd2ZiRWLLJIFv\CCrbnPy[YF{\XNidHjlJIFjfW6mYX7j[UBw\iCESV2=M2W5SFI2OzR7M{C3
SNU-2535M{LF[Wdzd3e2aDDpcohq[mm2b4L5JIF{e2G7Mmr0glExKM7:TR?=NGnKW45KSzVyPUOzMlEhdk1?MlP6NlY5PDl4M{e=
SNU-2535MUHLbY5ie2ViYYPzZZk>MmLiglEh|ryPM{XNS4lvcGmkaYTzJJRp\SCyaH;zdIhwenmuYYTpc44hd2ZiQVzLJIFv\CCrdIOg[I94dnO2cnXhcUBud2ynY4Xs[ZMhTVKNMT:yJIFv\CCDS2S=NFzUXW4zPjh2OU[zOy=>

... Click to View More Cell Line Experimental Data

In vivo Oral administration of CH5424802 dose-dependently inhibits tumor growth with an ED50 of 0.46 mg/kg and tumor regression. Treatment of 20 mg/kg CH5424802 reveals rapid tumor regression by 168%, the tumor volume in any mouse is <30 mm3 after 11 days of treatment (at day 28), a potent antitumor effect is maintained, and tumor regrowth does not occur throughout the 4-week drug-free period. The half-life and the oral bioavailability of CH5424802 in mice are 8.6 hours and 70.8%, respectively. At a repeated dose of 6 mg/kg, the mean plasma levels reached 1.7, 1.5, and 0.3 nM at 2, 7, and 24 hours post-dose, respectively. Administration of CH5424802 leads to tumor growth prevention and tumor regression. Tumor growth inhibition at 20 mg/kg is 119% for KARPAS-299 and 104% for NB-1 on day 20. CH5424802 inhibits the phosphorylation of STAT3 in a dose-dependent manner (2–20 mg/kg). A partial decrease in AKT phosphorylation is also observed in CH5424802-treated xenograft tumors. [1]
Features

Protocol(Only for Reference)

Kinase Assay: [1]

Kinase inhibitory assays in Vitro The inhibitory ability against each kinase except for MEK1 and Raf-1 is evaluated by examining their ability to phosphorylate various substrate peptides in the presence of CH5424802 using time-resolved fluorescence resonance energy transfer (TR-FRET) assay or fluorescence polarization (FP) assay. The inhibitory activity against MEK1 is evaluated by quantitative analysis of the phosphorylation of a substrate peptide by a recombinant ERK2 protein in the presence of CH5424802. The inhibitory activity against Raf-1 is evaluated by examining the ability of the kinases to phosphorylate MEK1 in the presence of CH5424802.

Cell Assay: [1]

Cell lines NSCLC, A549 and HCC827 cell lines
Concentrations 0-1 μM
Incubation Time 5 days
Method Cells including NSCLC, A549 and HCC827 are seeded in 96-well plates overnight and incubated with various concentrations of CH5424802 for the indicated time. For spheroid cell growth inhibition assay, cells are seeded on spheroid plates, incubated overnight, and then treated with compound for the indicated times. The viable cells are measured by the Luminescent Cell Viability Assay. Caspase-3/7 assay is evaluated using the Caspase-Glo 3/7 Assay Kit.

Animal Study: [1]

Animal Models SCID or nude mice bearing NCI-H2228
Formulation 0.02 N HCl, 10% DMSO, 10% Cremophor EL, 15% PEG400, and 15% HPCD (2-hydroxypropyl-β-cyclodextrin)
Dosages 20 mg/kg
Administration Oral administration

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)0.020.151.80.40.0810
Body Surface Area (m2)0.0070.0250.150.050.020.5
Km factor36128520
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Sakamoto H, et al. Cancer Cell. 2011, 19(5), 679-690.

[2] Kinoshita K, et al. Bioorg Med Chem. 2012, 20(3), 1271-1280.

Clinical Trial Information( data from http://clinicaltrials.gov, updated on 2016-07-30)

NCT Number Recruitment Conditions Sponsor
/Collaborators
Start Date Phases
NCT02314481 Not yet recruiting Non-small Cell Lung Cancer University College, London|Hoffmann-La Roche January 2017 Phase 2
NCT02838420 Recruiting Anaplastic Lymphoma Kinase-positive Non-small Cell Lung Cancer Hoffmann-La Roche July 2016 Phase 3
NCT02621047 Recruiting Hepatic Impairment Hoffmann-La Roche November 2015 Phase 1
NCT02604342 Recruiting Anaplastic Lymphoma Kinase-positive Non-small Cell Lung Cancer Hoffmann-La Roche November 2015 Phase 3
NCT02521051 Recruiting Non-Small Cell Lung Cancer (NSCLC) Massachusetts General Hospital|Genentech, Inc. October 2015 Phase 1|Phase 2

view more

Chemical Information

Download Alectinib (CH5424802) SDF
Molecular Weight (MW) 482.62
Formula

C30H34N4O2

CAS No. 1256580-46-7
Storage 3 years -20℃powder
6 months-80℃in solvent
Synonyms AF-802,RG-7853
Solubility (25°C) * In vitro DMSO 0.5 mg/mL warming (1.03 mM)
Water <1 mg/mL (<1 mM)
Ethanol <1 mg/mL (<1 mM)
In vivo 30% PEG400+0.5% Tween80+5% propylene glycol 30 mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
Chemical Name 9-ethyl-6,6-dimethyl-8-(4-morpholinopiperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

* Indicates a Required Field

Related ALK Products

  • PF-06463922

    PF-06463922 is a potent, dual ALK/ROS1 inhibitor with Ki of <0.02 nM, <0.07 nM, and 0.7 nM for ROS1, ALK (WT), and ALK (L1196M), respectively. Phase 1.

  • Erlotinib

    Erlotinib is an EGFR inhibitor with IC50 of 2 nM, >1000-fold more sensitive for EGFR than human c-Src or v-Abl.

  • R428 (BGB324)

    R428 (BGB324) is an inhibitor of Axl with IC50 of 14 nM, >100-fold selective for Axl versus Abl. Selectivty for Axl is also greater than Mer and Tyro3 (50-to-100- fold more selective) and InsR, EGFR, HER2, and PDGFRβ (100- fold more selective).

  • TAE684 (NVP-TAE684)

    TAE684 (NVP-TAE684) is a potent and selective ALK inhibitor with IC50 of 3 nM in a cell-free assay, 100-fold more sensitive for ALK than InsR.

  • GSK1838705A

    GSK1838705A is a potent IGF-1R inhibitor with IC50 of 2.0 nM, modestly potent to IR and ALK with IC50 of 1.6 nM and 0.5 nM, respectively, and little activity to other protein kinases.

    Features:A small-molecule kinase inhibitor of IGF-1R and the insulin receptor.

  • AP26113

    AP26113 is a potent ALK inhibitor with IC50 of 0.62 nM in a cell-free assay, demonstrated ability overcome Crizotinib resistance mediated by a L1196M mutation. Phase 2.

    Features:At least 10-fold more potent and selective in ALK inhibition relative to crizotinib.

  • ASP3026

    ASP3026 is a novel and selective inhibitor for ALK with IC50 of 3.5 nM. Phase 1.

  • AZD3463

    AZD3463 is a novel orally bioavailable ALK inhibitor with Ki of 0.75 nM, which also inhibits IGF1R with equivalent potency.

  • Ceritinib (LDK378)

    Ceritinib (LDK378) is potent inhibitor against ALK with IC50 of 0.2 nM in cell-free assays, shows 40- and 35-fold selectivity against IGF-1R and InsR, respectively. Phase 3.

    Features:Does not cross react with c-Met, and has an improved in vivo glucose homeostasis profile relative to TAE684. May be active in Crizotinib-relapsed tumors.

  • Gefitinib (ZD1839)

    Gefitinib (ZD-1839) is an EGFR inhibitor for Tyr1173, Tyr992, Tyr1173 and Tyr992 in the NR6wtEGFR and NR6W cells with IC50 of 37 nM, 37nM, 26 nM and 57 nM, respectively.

    Features:A potent EGFR tyrosine kinase inhibitor.

Recently Viewed Items

Tags: buy Alectinib (CH5424802) | Alectinib (CH5424802) supplier | purchase Alectinib (CH5424802) | Alectinib (CH5424802) cost | Alectinib (CH5424802) manufacturer | order Alectinib (CH5424802) | Alectinib (CH5424802) distributor
×
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
Contact Us