Varlitinib (ARRY-543; ARRY-334543; ASLAN-001)

Alias: ARRY334543; ASLAN001; ASLAN-001; ASLAN 001; AR 00334543; ARRY-334543; ARRY543; ARRY-543; ARRY 543

Cat No.:V0570 Purity: ≥98%

COA Product Data Instructions for use SDS

Varlitinib (ARRY-543; ARRY-334543; ASLAN-001) Chemical Structure CAS No.: 845272-21-1
Product category: EGFR

This product is for research use only, not for human use. We do not sell to patients.

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1-708-310-1919 sales@invivochem.com

Other Forms of Varlitinib (ARRY-543; ARRY-334543; ASLAN-001):

Varlitinib Tosylate (ARRY543; ASLAN001)

Official Supplier of:

Top Publications Citing lnvivochem Products

Nature 2021, 597(7874):119-125.

Cell 2020,183:1202-1218.e25.

Science Adv 2022: 8, eabm9427.

Nature 597, 119–125 (2021)

Cell Stem Cell 2020,26(6):845-861.e12.

Science Trans Med 2023,15(701):eadd7872.

STTT 2023,8(1):91.

Cell Reports 2023,42(4):112313

Science Trans Med 2023, 15: eadd7872.

Cancer Cell 2021,39(4):529-547.e7.

Cancer Discov 2022,12(4):1106-1127.

Immunity 2023,56(3):620-634.e11.

J Am Chem Soc 2022,144:21831-21836.

Cell 2020,183:1202-1218.e25.

Science Adv 2022:8,eabm9427.

Nature 2021,597(7874):119-125.

Cell 2020,183:1202-1218.e25.

PNAS Nexus 2022,1(3):pgac063.

ACS Nano 2023,17(10):9110-9125.

Biomaterial 2023 Sep16:302:122333.

Purity & Quality Control Documentation

Current batch：

Purity: ≥98%

COA

MSDS

Instructions

Product Description
Bioactivity & Protocols
Physicochemical Properties
Solubility Data
Calculators
Clinical Trial Information
Biological Data

Product Description

Varlitinib (formerly also known as ARRY543; ARRY-334543; ASLAN001) is a novel, potent, orally bioavailable, selective and reversible ErbB1 (EGFR) and ErbB2 (HER2) inhibitor with potential antitumor activity. ErbB1 (EGFR) and ErbB2 (HER2) are inhibited with IC50 values of 2 nM and 7 nM, respectively.

Biological Activity I Assay Protocols (From Reference)

Targets

HER1 (IC50 = 7 nM); HER2 (IC50 = 2 nM); HER4 (IC50 = 4 nM)

ln Vitro

In vitro activity: ARRY334543 behaves as a reversible ATP-competitive inhibitor with nanomolar potency (Ki=1 nM) both in vitro and in cell-based proliferation assays using A431 and BT-474 cells. ARRY334543 is an AKT pathway inhibitor in cells that contains active ErbB-2 receptors. ARRY334543 suppresses ErbB-2 and ErbB-1 phosphorylation in human cancer cells, such as BT-474 with IC50 of 43 nM) and A431 with IC50 of 36 nM) that overexpress ErbB-2 and ErbB-1, respectively

Kinase Assay: Varlitinib (ARRY-334543; ASLAN001) is a novel, potent, reversible, small molecule pan-EGFR inhibitor with IC50s of 7, 2, 4 nM for HER1, HER2 and HER4, respectively.

Cell Assay: In cell-based assays using tumor cells that over-express EGFR (A431) or ErbB-2 (BT474), Varlitinib (ARRY-334543) potently inhibits substrate phosphorylation. Varlitinib is shown to be highly selective for EGFR/ErbB-2, and does not show any significant activity when screened against a panel of 104 kinases

ln Vivo

Varlitinib (ARRY-334543) treatment significantly slows the growth of tumors; full tumor regression is seen at dosages of 100 mg/kg twice daily. The phosphorylation of HER1-3, RAS/RAF/MEK/MAPK, p70S6K, S6 ribosomal, 4EBP1, Cdk-2, Cdc-2, and retinoblastoma is significantly inhibited after five days of Varlitinib treatment. Treatment with varlitinib causes survivin to significantly decrease while Caspase 3 cleavage products increase simultaneously[1]. Varlitinib (ARRY-334543), when taken orally twice a day for 21 days, significantly inhibits the growth of A431-derived tumors in murine xenograft models at doses of 25, 50, and 100 mg/kg[2].

Enzyme Assay

Varlitinib (ARRY-334543; ASLAN001) is a novel, potent, reversible, small molecule pan-EGFR inhibitor with IC50s of 7, 2, 4 nM for HER1, HER2 and HER4, respectively.

Cell Assay

Varlitinib (ARRY-334543) potently inhibits substrate phosphorylation in cell-based assays with tumor cells that overexpress EGFR (A431) or ErbB-2 (BT474). When tested against a panel of 104 kinases, varlitinib is found to be highly selective for EGFR/ErbB-2 and to exhibit no discernible activity.

Animal Protocol

Mice: In SCID mice (HCC29-0909A) bearing patient-derived HCC xenografts co-expressing HER1, HER2, and HER3 receptors, the effects of varlitinib are examined. When the tumors in mice get to be as big as 100–150 mm³, they are treated with varlitinib. Twice a week, tumor volumes are computed and tumor sizes are measured[1].

References

[1]. Varlitinib to demonstrate anti-tumour efficacy in patient-derived hepatocellular carcinoma xenograft models. Journal of Clinical Oncology 34, no. 15_suppl

[2]. ARRY-334543, A potent, orally active small molecule inhibitor of EGFR and ErbB-2.Proc Amer Assoc Cancer Res (2005) 65 (9_Supplement): 801.

These protocols are for reference only. InvivoChem does not independently validate these methods.

Physicochemical Properties

Molecular Formula

C22H19CLN6O2S

Molecular Weight

466.94

Exact Mass

466.10

Elemental Analysis

C, 56.59; H, 4.10; Cl, 7.59; N, 18.00; O, 6.85; S, 6.87

CAS #

845272-21-1

Related CAS #

Varlitinib tosylate;1146629-86-8

Appearance

White solid powder

SMILES

C[C@@H]1COC(=N1)NC2=CC3=C(C=C2)N=CN=C3NC4=CC(=C(C=C4)OCC5=NC=CS5)Cl

InChi Key

UWXSAYUXVSFDBQ-CYBMUJFWSA-N

InChi Code

InChI=1S/C22H19ClN6O2S/c1-13-10-31-22(27-13)29-14-2-4-18-16(8-14)21(26-12-25-18)28-15-3-5-19(17(23)9-15)30-11-20-24-6-7-32-20/h2-9,12-13H,10-11H2,1H3,(H,27,29)(H,25,26,28)/t13-/m1/s1

Chemical Name

4-N-[3-chloro-4-(1,3-thiazol-2-ylmethoxy)phenyl]-6-N-[(4R)-4-methyl-4,5-dihydro-1,3-oxazol-2-yl]quinazoline-4,6-diamine

Synonyms

ARRY334543; ASLAN001; ASLAN-001; ASLAN 001; AR 00334543; ARRY-334543; ARRY543; ARRY-543; ARRY 543

HS Tariff Code

2934.99.9001

Storage

Powder -20°C 3 years

4°C 2 years

In solvent -80°C 6 months

-20°C 1 month

Shipping Condition

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility Data

Solubility (In Vitro)

DMSO: ~6 mg/mL (~12.8 mM)

Water: <1 mg/mL

Ethanol: <1 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.35 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

Solubility in Formulation 2: ≥ 2.08 mg/mL (4.45 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 3: 2.08 mg/mL (4.45 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

(Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.1416 mL	10.7080 mL	21.4160 mL
	5 mM	0.4283 mL	2.1416 mL	4.2832 mL
	10 mM	0.2142 mL	1.0708 mL	2.1416 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

Calculator

Mass

Concentration

Volume

Molecular Weight*

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Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

Calculate the Mass of a compound required to prepare a solution of known volume and concentration
Calculate the Volume of solution required to dissolve a compound of known mass to a desired concentration
Calculate the Concentration of a solution resulting from a known mass of compound in a specific volume

See Example

An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?

Enter 350.26 in the Molecular Weight (MW) box
Enter 10 in the Concentration box and choose the correct unit (mM)
Enter 5 in the Volume box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Concentration (Start)

Volume (Start)

Concentration (End)

Volume (End)

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Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:

Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
Enter 25 into the Concentration (End) box and select the correct unit (mM)
Enter 25 into the Volume (End) box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box

Molecular formula

Total molecular weight

g/mol

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Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4 c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Volume (to add to vial)

Mass (in vial)

Desired Reconstitution Concentration

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Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
Click the “Calculate” button
The answer appears in the Volume (to add to vial) box

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal to make 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 in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)

% DMSO

% Tween 80

% ddH₂O

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Calculation results

Working concentration： mg/mL；

Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O，mix and clarify.

Note： (1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.

Clinical Trial Information

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT03368846	Completed	Drug: Varlitinib	Healthy Volunteers	ASLAN Pharmaceuticals	November 23, 2017	Phase 1
NCT03231176	Completed	Drug: Varlitinib Drug: Capecitabine	Biliary Tract Cancer	ASLAN Pharmaceuticals	December 19, 2017	Phase 2
NCT03093870	Completed	Drug: Varlitinib Drug: Capecitabine	Biliary Tract Cancer	ASLAN Pharmaceuticals	July 4, 2017	Phase 2 Phase 3
NCT05400915	Completed	Drug: Variltinib, Paclitaxel	Gastric Cancer	Yonsei University	July 23, 2019	Phase 1 Phase 2
NCT03082053	Recruiting	Drug: varlitinib Drug: capecitabine	Advanced or Metastatic Solid Tumors Advanced or Metastatic Biliary Tract Cancer	ASLAN Pharmaceuticals	January 31, 2017	Phase 1

Biological Data

Varlitinibexerts anti-proliferation ability and induces apoptosis in MDA-MB-453 and MDA-MB-468 cells but not MDA-MB-231 cells.Cancers (Basel). 2019 Jan; 11(1): 105.
Varlitinibinhibits MEK/ERK and Akt pathway in TNBC cells.Cancers (Basel). 2019 Jan; 11(1): 105.
ERK signaling mediatesvarlitinib-induced apoptosis in TNBC cells.Cancers (Basel). 2019 Jan; 11(1): 105.
Varlitinibinhibits tumor growth of TNBC.Cancers (Basel). 2019 Jan; 11(1): 105.

Varlitinib

Varlitinib reduces the abilities of migration, invasion and mammosphere formation of TNBC cells. (A–C) MDA-MB-231 and MDA-MB-468 cells were treated with varlitinib or DMSO for subsequent migration (A), invasion (B) and mammosphere assays (C).Cancers (Basel). 2019 Jan; 11(1): 105.