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Anlotinib (AL3818) dihydrochloride

Name: Anlotinib (AL3818) dihydrochloride
Brand: Selleck Chemicals
SKU: S8726
Rating: 5 (21 reviews)

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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VEGFR Signaling Pathway Map

Biological Activity

Description

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?=

Click to View More Cell Line Experimental Data

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 t_1/2 (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

References

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
Storage	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)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

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.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
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Dilution Calculator Molecular Weight Calculator

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

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