Varlitinib | ARRY-543 | ASLAN-001 | EGFR Inhibtior | CAS#845272-21-1

MedKoo Cat#: 205660 | Name: Varlitinib

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Varlitinib, also known as ARRY-543 and ASLAN001, is an orally bioavailable inhibitor of the epidermal growth factor receptor family with potential antineoplastic activity. Varlitinib selectively and reversibly binds to both EGFR (ErbB-1) and Her-2/neu (ErbB-2) and prevents their phosphorylation and activation, which may result in inhibition of the associated signal transduction pathways, inhibition of cellular proliferation and cell death. EGFR and Her-2 play important roles in cell proliferation and differentiation and are upregulated in various human tumor cell types.

Chemical Structure

Varlitinib

CAS#845272-21-1 (free base)

Theoretical Analysis

MedKoo Cat#: 205660

Name: Varlitinib

CAS#: 845272-21-1 (free base)

Chemical Formula: C22H19ClN6O2S

Exact Mass: 466.0979

Molecular Weight: 466.94

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

Price and Availability

Size	Price	Availability
10mg	USD 90.00	Ready to ship
25mg	USD 150.00	Ready to ship
50mg	USD 250.00	Ready to ship
100mg	USD 450.00	Ready to ship
200mg	USD 750.00	Ready to ship
500mg	USD 1,650.00	Ready to ship
1g	USD 2,950.00	Ready to ship
2g	USD 5,250.00	Ready to ship

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Related CAS #

1146629-86-8 (Tosylate) 845272-21-1 (free base)

Synonym

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

IUPAC/Chemical Name

(R)-N4-(3-chloro-4-(thiazol-2-ylmethoxy)phenyl)-N6-(4-methyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine.

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

SMILES Code

C[C@H]1N=C(NC2=CC3=C(NC4=CC=C(OCC5=NC=CS5)C(Cl)=C4)N=CN=C3C=C2)OC1

Appearance

White solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

ARRY-543 is a novel, oral ErbB family inhibitor that, unlike approved ErbB inhibitors, targets all members of the ErbB family, including ErbB3, either directly or indirectly, and has potential advantages in treating tumors that signal through multiple ErbB family members. ARRY-543 showed benefit in preclinical tumor models that signal through multiple ErbB family members, as well as its efficacy in preclinical models when compared to, and combined with, Herceptin (trastuzumab), Xeloda (capecitabine) and Taxotere (docetaxel) Â– widely used treatments for solid tumors.

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot# KB21128

QC Data

View QC data: current batch, Lot# KB21128

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

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

In vitro activity:

In this study, the efficacy of varlitinib, a reversible small molecule pan-HER inhibitor in TNBC was evaluated. To explore varlitinib’s anti-tumor activity, cells were treated with varlitinib at various concentrations. Compared with MCF 10A cell lines, most of the cell lines exhibited lower IC50 except MDA-MB-231 cells (Figure 1B and Figure S1). Moreover, varlitinib significantly induced cell apoptosis in MDA-MB-453 and MDA-MB-468 cells but not in MDA-MB-231 cells (Figure 1B,C). Data showed varlitinib reduced pEGFR, pHER3 and pHER4 in MDA-MB-468 cells as well as reduced pHER2 in SK-BR-3 cells (Figure 2A,B). Activation of HER receptors leads to the activation of downstream pathways including RAS/RAF/MEK/ERK and PI3K/Akt signaling. The western blot results demonstrated that varlitinib treatment inhibited EGFR, AKT, MEK and ERK activation in MDA-MB-453 and MDA-MB-468 cells. In addition, varlitinib treatment also resulted in increased levels of cleaved PARP and cleaved Caspase-3 in these TNBC cell lines. Conversely, varlitinib did not inhibit MEK/ERK signaling in MDA-MB-231 cells (Figure 2C). Our results showed that varlitinib treatment inhibited cell migration, invasion and mammosphere formation of MDA-MB-231 and MDA-MB-468 cells (Figure 4A–C). Cancers (Basel). 2019 Jan; 11(1): 105. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356324/

In vivo activity:

Nude mice were subcutaneously implanted with MDA-MB-468 cells to evaluate anti-tumor activity of varlitinib. Once xenograft tumor sizes reached 200 mm3 varlitinib were orally administered. Varlitinib suppressed tumor growth in MDA-MB-468 xenograft mice with no effect on body weight (Figure 5A–C). In comparison to the control group, varlitinib treatment significantly suppressed EGFR and ERK activation with increased PARP cleavage (Figure 5D). Immunohistochemical staining was performed to further examine protein expression and localization within the xenograft tumors. The results showed that varlitinib treatment reduced EGFR and ERK phosphorylation and elicited cell apoptosis with M30 staining (Figure 5D,E). These results demonstrated varlitinib exerting anti-tumor activity in TNBC via the inhibition of HER receptor and downstream signaling. Cancers (Basel). 2019 Jan; 11(1): 105. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356324/

	Solvent	mg/mL	mM
Solubility
	DMSO	20.0	43.55

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 466.94 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Liu CY, Chu PY, Huang CT, Chen JL, Yang HP, Wang WL, Lau KY, Lee CH, Lan TY, Huang TT, Lin PH, Dai MS, Tseng LM. Varlitinib Downregulates HER/ERK Signaling and Induces Apoptosis in Triple Negative Breast Cancer Cells. Cancers (Basel). 2019 Jan 17;11(1):105. doi: 10.3390/cancers11010105. PMID: 30658422; PMCID: PMC6356324. 2. Dokduang H, Jamnongkarn W, Promraksa B, Suksawat M, Padthaisong S, Thanee M, Phetcharaburanin J, Namwat N, Sangkhamanon S, Titapun A, Khuntikeo N, Klanrit P, Loilome W. In vitro and in vivo Anti-Tumor Effects of Pan-HER Inhibitor Varlitinib on Cholangiocarcinoma Cell Lines. Drug Des Devel Ther. 2020 Jun 11;14:2319-2334. doi: 10.2147/DDDT.S250061. PMID: 32606601; PMCID: PMC7296552. 3. Liu CY, Chu PY, Huang CT, Chen JL, Yang HP, Wang WL, Lau KY, Lee CH, Lan TY, Huang TT, Lin PH, Dai MS, Tseng LM. Varlitinib Downregulates HER/ERK Signaling and Induces Apoptosis in Triple Negative Breast Cancer Cells. Cancers (Basel). 2019 Jan 17;11(1):105. doi: 10.3390/cancers11010105. PMID: 30658422; PMCID: PMC6356324. 4. Dokduang H, Jamnongkarn W, Promraksa B, Suksawat M, Padthaisong S, Thanee M, Phetcharaburanin J, Namwat N, Sangkhamanon S, Titapun A, Khuntikeo N, Klanrit P, Loilome W. In vitro and in vivo Anti-Tumor Effects of Pan-HER Inhibitor Varlitinib on Cholangiocarcinoma Cell Lines. Drug Des Devel Ther. 2020 Jun 11;14:2319-2334. doi: 10.2147/DDDT.S250061. PMID: 32606601; PMCID: PMC7296552.

In vitro protocol:

In vivo protocol:

1: Koo DH, Jung M, Kim YH, Jeung HC, Zang DY, Bae WK, Kim H, Kim HS, Lee CK, Kwon WS, Chung HC, Rha SY. Varlitinib and Paclitaxel for EGFR/HER2 Co-expressing Advanced Gastric Cancer: A Multicenter Phase Ib/II Study (K-MASTER-13). Cancer Res Treat. 2024 Oct;56(4):1136-1145. doi: 10.4143/crt.2023.1324. Epub 2024 Apr 29. PMID: 38697849; PMCID: PMC11491253. 2: Tanveer F, Ilyas A, Syed B, Hashim Z, Ahmed A, Zarina S. Differential Protein Expression in Response to Varlitinib Treatment in Oral Cancer Cell Line: an In Vitro Therapeutic Approach. Appl Biochem Biotechnol. 2024 Apr;196(4):2110-2121. doi: 10.1007/s12010-023-04642-3. Epub 2023 Jul 20. PMID: 37470935. 3: Hu X, Zhang Y, Yu H, Zhao Y, Sun X, Li Q, Wang Y. The role of YAP1 in survival prediction, immune modulation, and drug response: A pan-cancer perspective. Front Immunol. 2022 Nov 21;13:1012173. doi: 10.3389/fimmu.2022.1012173. PMID: 36479120; PMCID: PMC9719955. 4: Kim J, Kim SJ, Jeong HR, Park JH, Moon M, Hoe HS. Inhibiting EGFR/HER-2 ameliorates neuroinflammatory responses and the early stage of tau pathology through DYRK1A. Front Immunol. 2022 Oct 20;13:903309. doi: 10.3389/fimmu.2022.903309. PMID: 36341365; PMCID: PMC9632417. 5: Beaumont H, Faye N, Iannessi A, Chamorey E, Klifa C, Hsieh CY. Differences in sensitivity to new therapies between primary and metastatic breast cancer: A need to stratify the tumor response? Cancer Med. 2023 Feb;12(3):3112-3122. doi: 10.1002/cam4.5236. Epub 2022 Sep 13. PMID: 36098367; PMCID: PMC9939226. 6: Lee MX, Wong ALA, Ow S, Sundar R, Tan DSP, Soo RA, Chee CE, Lim JSJ, Yong WP, Lim SE, Goh BC, Wang L, Lee SC. Phase Ib Dose-Finding Study of Varlitinib Combined with Weekly Paclitaxel With or Without Carboplatin ± Trastuzumab in Advanced Solid Tumors. Target Oncol. 2022 Mar;17(2):141-151. doi: 10.1007/s11523-022-00867-0. Epub 2022 Feb 23. PMID: 35195837; PMCID: PMC8995271. 7: Javle MM, Oh DY, Ikeda M, Yong WP, Hsu K, Lindmark B, McIntyre N, Firth C. Varlitinib plus capecitabine in second-line advanced biliary tract cancer: a randomized, phase II study (TreeTopp). ESMO Open. 2022 Feb;7(1):100314. doi: 10.1016/j.esmoop.2021.100314. Epub 2021 Dec 15. PMID: 34922298; PMCID: PMC8685988. 8: Prawira A, Le TBU, Ho RZW, Huynh H. Upregulation of the ErbB family by EZH2 in hepatocellular carcinoma confers resistance to FGFR inhibitor. J Cancer Res Clin Oncol. 2021 Oct;147(10):2955-2968. doi: 10.1007/s00432-021-03703-6. Epub 2021 Jun 22. PMID: 34156519; PMCID: PMC8397639. 9: Tanveer F, Anwar MF, Siraj B, Zarina S. Evaluation of anti-EGFR potential of quinazoline derivatives using molecular docking: An in silico approach. Biotechnol Appl Biochem. 2022 Jun;69(3):1226-1237. doi: 10.1002/bab.2199. Epub 2021 Jun 3. PMID: 34028091. 10: Dokduang H, Jamnongkarn W, Promraksa B, Suksawat M, Padthaisong S, Thanee M, Phetcharaburanin J, Namwat N, Sangkhamanon S, Titapun A, Khuntikeo N, Klanrit P, Loilome W. In vitro and in vivo Anti-Tumor Effects of Pan-HER Inhibitor Varlitinib on Cholangiocarcinoma Cell Lines. Drug Des Devel Ther. 2020 Jun 11;14:2319-2334. doi: 10.2147/DDDT.S250061. PMID: 32606601; PMCID: PMC7296552. 11: Coelho SC, Reis DP, Pereira MC, Coelho MAN. Doxorubicin and Varlitinib Delivery by Functionalized Gold Nanoparticles Against Human Pancreatic Adenocarcinoma. Pharmaceutics. 2019 Oct 24;11(11):551. doi: 10.3390/pharmaceutics11110551. PMID: 31652942; PMCID: PMC6920992. 12: Liu CY, Chu PY, Huang CT, Chen JL, Yang HP, Wang WL, Lau KY, Lee CH, Lan TY, Huang TT, Lin PH, Dai MS, Tseng LM. Varlitinib Downregulates HER/ERK Signaling and Induces Apoptosis in Triple Negative Breast Cancer Cells. Cancers (Basel). 2019 Jan 17;11(1):105. doi: 10.3390/cancers11010105. PMID: 30658422; PMCID: PMC6356324. 13: Coelho SC, Reis DP, Pereira MC, Coelho MAN. Gold Nanoparticles for Targeting Varlitinib to Human Pancreatic Cancer Cells. Pharmaceutics. 2018 Jul 12;10(3):91. doi: 10.3390/pharmaceutics10030091. PMID: 30002279; PMCID: PMC6161021.