Anlotinib (AL3818) dihydrochloride

Catalog No.S8726

For research use only.

Anlotinib (AL3818) is a highly potent and selective VEGFR2 inhibitor with IC50 less than 1 nM. It has broad-spectrum antitumor potential in clinical trials. Please use saline solution rather than PBS for dilutions. PBS may cause precipitation.

Anlotinib (AL3818) dihydrochloride Chemical Structure

CAS No. 1360460-82-7

Selleck's Anlotinib (AL3818) dihydrochloride has been cited by 21 publications

Purity & Quality Control

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Biological Activity

Description Anlotinib (AL3818) is a highly potent and selective VEGFR2 inhibitor with IC50 less than 1 nM. It has broad-spectrum antitumor potential in clinical trials. Please use saline solution rather than PBS for dilutions. PBS may cause precipitation.
Targets
VEGFR2 [1]
(Cell-free assay)
VEGFR3 [1]
(Cell-free assay)
c-Kit [1]
(Cell-free assay)
c-Kit [1]
(Cell-free assay)
c-Kit [1]
(Cell-free assay)
0.2 nM 0.7 nM 14.8 nM 14.8 nM 14.8 nM
In vitro

Anlotinib occupies the ATP-binding pocket of VEGFR2 tyrosine kinase and shows high selectivity and inhibitory potency (IC 50 <1 nmol/L) for VEGFR2 relative to other tyrosine kinases. Anlotinib inhibits VEGFR2 and VEGFR3 with IC50 values of 0.2 and 0.7 nmol/L, respectively. The inhibitory potency of anlotinib against VEGFR1 is lower, with an IC50 value of 26.9 nmol/L. The IC50 values of anlotinib for inhibition of the PDGFR-related kinases c-Kit and PDGFRβ are 14.8 and 115.0 nmol/L, respectively. Anlotinib has little effect on the activity of other kinases, including c-Met, c-Src, EGFR and HER2, even at a concentration of 2000 nmol/L. Anlotinib inhibits VEGF-induced signaling and cell proliferation in HUVEC with picomolar IC50 values. However, micromolar concentrations of anlotinib are required to inhibit tumor cell proliferation directly in vitro. Anlotinib significantly inhibits HUVEC migration and tube formation; it also inhibits microvessel growth from explants of rat aorta in vitro[1].

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
U-87MG M4PuPWZ2dmO2aX;uJIF{e2G7 M{PXVVAvODFuIECuNUwhOSxiMUCgZY5lKDFyMDFOwG0> MV[xMlUhcA>? M4jEbYlvcGmkaYTl[EBRTEeILVLCMZN1cW23bHH0[YQheGixc4Doc5J6dGG2aX;uJI9nKFCGR1\S{tItKEGNVDDhcoQhTVKNIHnuJHUuQDePRzDj[Yxtew>? MXK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR2Nki1N{c,Ojl2NE[4OVM9N2F-
Mo7e MlGxSpVv[3Srb36gZZN{[Xl? M3zNXVAvODFuIECuNUwhOSxiMUCgZY5lKDFyMDFOwG0> NX73WW94OS53IHi= MkiyRY5td3SrbnniJIlvcGmkaYTl[EBUS0ckgKCx5qCRe3SrbYXsZZRm\CCyaH;zdIhwenmuYYTpc44hd2ZiY,MAlGtqfCxiQVvUJIFv\CCHUlugbY4hVW95ZTDj[Yxtew>? NXS4O|JsRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0OFY5PTNpPkK5OFQ3QDV|PD;hQi=>
HUVEC NWTiTpBoTnWwY4Tpc44h[XO|YYm= NIPhOVQxNjBzLDCwMlEtKDFuIEGwJIFv\CBzMECg{txO MoHVNU42KGh? MXfhcoxwfGmwaXKgbY5pcWKrdHXkJHZGT0ckgKDzeIlufWyjdHXkJIlvfHKjY3XscJVt[XJicHjvd5Bpd3K7bHH0bY9vKG:oIG\FS2ZTOiCrbjDhJINwdmOnboTyZZRqd28kgKDk[ZBmdmSnboSge4F6KGmwIFjVWmVEKHerdHigZUB{fWKwYX7vcY9t[XJiSVO1NEB3[Wy3ZR?= Mm\BQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2NE[4OVMoRjJ7NES2PFU{RC:jPh?=
A549 NF3XUXJE\WyuII\pZYJqdGm2eTDhd5NigQ>? MkHKNlQtKDR6IHHu[EA4OuLCiXi= M1jmcmlEPTB;NkSuPFIh|ryP78{IeF0zPCCq78{JP{BKSzVyPUOwMlM1KM7:Tf-8jJQ:PDhiaP-8jVshUUN3ME2xO{4zQSEQvF5vwKh1RTd{IHlvwKk> Mli1QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzB5NUWyOFIoRjNyN{W1NlQzRC:jPh?=
NCI-H1975 NFjiPYNE\WyuII\pZYJqdGm2eTDhd5NigQ>? MWi45qCK|rypL33s M1jXTFI16oDLaB?= MlnuR4VtdCC4aXHibYxqfHlid3HzJIRm[3KnYYPl[EBz\W2jcnvhZox6 MofoQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzB6N{G1NlYoRjNyOEexOVI3RC:jPh?=
Calu-1 MVrD[YxtKH[rYXLpcIl1gSCjc4PhfS=> MkThNlQtKDR6IHHu[EA4OuLCiXi= MnT0TWM2OD14MT6yN{DPxE4xvJj0QVI1KGkxvJm7JGlEPTB;M{[uPEDPxE4xvJj0QVQ5KGkxvJm7JGlEPTB;MkiuOlQh|ryP78{IeF04OiCq78{J Mnr6QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzB5NUWyOFIoRjNyN{W1NlQzRC:jPh?=
Assay
Methods Test Index PMID
Western blot TP53 / Cleaved-caspase 3 / Cleaved PARP ; Beclin-1 / LC3-I / LC3-II ; Akt / p-Akt / mTOR / p-mTOR 30139768 30755242
Immunofluorescence LC3-II 30755242
Growth inhibition assay Cell viability 30755242
In vivo Anlotinib decreases vascular density in tumor tissue in vivo. Compared with the well-known tyrosine kinase inhibitor sunitinib, once-daily oral dose of anlotinib shows broader and stronger in vivo antitumor efficacy and, in some models, causes tumor regression in nude mice. It is well-tolerated in mice. Anlotinib is efficacious at doses (1.5‐6 mg/kg daily) that are significantly lower than effective doses of other TKI, which require doses of 20‐100 mg/kg to achieve significant inhibition of tumor growth in mice[1]. In vivo, anlotinib has showed broad activity against human tumor xenograft models of the colon (SW-620), ovarian (SK-OV-3), liver (SMMC-7721), renal (Caki-1), glioma (U87MG), and non-small cell lung (Calu-3) during dosing period. In Sprague-Dawley rats and beagle dogs, anlotinib is rapidly absorbed from the gastrointestinal tracks after oral administration. The oral bioavailability is 23-45 % in rats and 47-74 % in dogs. Anlotinib exhibits large volume of distribution in both species. In rats, primary tissues, such as the lung, kidneys, liver, and heart, exhibit significant higher exposure levels to anlotinib compared with that in plasma. The exposure level in the brain is comparable with the corresponding plasma level. In tumor-bearing mice, anlotinib concentrates 2.4-2.6 times in tumor tissue than in plasma. In human, anlotinib exhibits a quite long t1/2 (96 ± 17 h), which appeared to be dose-independent[2]. The terminal half-life of anlotinib in dogs (22.8±11.0 h) is longer than that in rats (5.1±1.6 h). This difference appeares to be mainly associated with an interspecies difference in total plasma clearance (rats, 5.35±1.31 L/h/kg; dogs, 0.40±0.06 L/h/kg). In human plasma, anlotinib is predominantly bound to albumin and lipoproteins, rather than to α1-acid glycoprotein or γ-globulins[3].

Protocol (from reference)

Kinase Assay:

[1]

  • Enzyme-linked immunosorbent assay:

    Inhibitory activity of anlotinib against tyrosine kinases was determined using ELISA. Reaction of ATP with tyrosine kinase was initiated in reaction buffer (50 mmol/L HEPES pH 7.4, 50 mmol/L MgCl2, 0.5 mmol/L MnCl2, 0.2 mmol/L Na3VO4, 1 mmol/L DTT) and incubated for 1 hour at 37°C in 96-well plates precoated with 20 μg/mL Poly(Glu,Tyr)4:1. The plate was incubated with PY99 antibody and then with HRP-conjugated anti-mouse IgG. After reaction with o-phenylenediamine solution and then termination with the addition of 2N H2SO4, absorbance was measured at 490 nm using a Synergy H4 Hybrid reader.

Cell Research:

[1]

  • Cell lines: HUVEC, Mo7e, U-87MG and A431 cells
  • Concentrations: 0-10 μM
  • Incubation Time: 1.5 h
  • Method:

    Serum-starved HUVEC, Mo7e, U-87MG and A431 cells are treated with different concentrations of test agents for 1.5 h and then stimulated with vascular endothelial growth factor (VEGF; 20 ng/mL), stem cell factor-1 (SCF-1; 2.5 ng/mL), platelet-derived growth factor-BB (PDGF-BB; 10 ng/mL), or epidermal growth factor (EGF; 10 ng/mL) for 10 min, respectively. Cell lysates are probed with the indicated antibodies.

Animal Research:

[1]

  • Animal Models: human colon cancer SW620 xenograft model(Balb/cA-nude mice, 5-6 weeks old)
  • Dosages: 0.75, 1.5, 3 and 6 mg/kg
  • Administration: oral

Solubility (25°C)

In vitro

DMSO 96 mg/mL
(199.85 mM)
Water 96 mg/mL
(199.85 mM)
Ethanol Insoluble

Chemical Information

Molecular Weight 480.36
Formula

C23H22FN3O3.2HCl

CAS No. 1360460-82-7
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CC1=CC2=C(N1)C=CC(=C2F)OC3=C4C=C(C(=CC4=NC=C3)OCC5(CC5)N)OC.Cl.Cl

In vivo Formulation Calculator (Clear solution)

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Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT04803851 Not yet recruiting Drug: Anlotinib plus AK105 Anlotinib|Anti-PD-1 Antibody|Advanced Pancreatic Cancer Peking Union Medical College Hospital March 2021 Phase 1|Phase 2
NCT02825563 Completed Drug: Anlotinib Advanced Cancer Chia Tai Tianqing Pharmaceutical Group Co. Ltd. June 2016 Phase 1
NCT02752516 Unknown status Drug: Anlotinib Cancer Chia Tai Tianqing Pharmaceutical Group Co. Ltd. April 27 2016 Phase 1
NCT02622932 Completed Drug: Anlotinib and 14C-labeled Anlotinib Advanced Solid Tumors Chia Tai Tianqing Pharmaceutical Group Co. Ltd. December 2 2015 Phase 1

(data from https://clinicaltrials.gov, updated on 2022-01-17)

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.

Handling Instructions

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