WZ4002 | CAS#1213269-23-8 | EGFR Inhibitor

MedKoo Cat#: 203170 | Name: WZ4002

Description:

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

WZ4002 is EGFR inhibitor against EGFR T790M (mutation of the gatekeeper T790 residue) which is detected in 50% of clinically resistant patients to gefitinib or erlotinib. WZ4002 has a basic chemical framework (covalent pyrimidine) which is different from that of other EGFR inhibitors. This agent is 30- to 100-fold more potent against EGFR T790M, and up to 100-fold less potent against wildtype EGFR, than quinazoline-based EGFR inhibitors (HKI-272 and CL-387,785) in vitro.

Chemical Structure

WZ4002

CAS# 1213269-23-8

Theoretical Analysis

MedKoo Cat#: 203170

Name: WZ4002

CAS#: 1213269-23-8

Chemical Formula: C25H27ClN6O3

Exact Mass: 494.1833

Molecular Weight: 494.97

Elemental Analysis: C, 60.66; H, 5.50; Cl, 7.16; N, 16.98; O, 9.70

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 425.00	Ready to ship
200mg	USD 750.00	Ready to ship
500mg	USD 1,250.00	Ready to ship

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Related CAS #

1213269-23-8 WZ4002 (HBr) WZ4002-hydroxy

Synonym

WZ4002; WZ-4002; WZ 4002.

IUPAC/Chemical Name

N-(3-((5-chloro-2-((2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)amino)pyrimidin-4-yl)oxy)phenyl)acrylamide

InChi Key

ITTRLTNMFYIYPA-UHFFFAOYSA-N

InChi Code

InChI=1S/C25H27ClN6O3/c1-4-23(33)28-17-6-5-7-19(14-17)35-24-20(26)16-27-25(30-24)29-21-9-8-18(15-22(21)34-3)32-12-10-31(2)11-13-32/h4-9,14-16H,1,10-13H2,2-3H3,(H,28,33)(H,27,29,30)

SMILES Code

C=CC(NC1=CC=CC(OC2=NC(NC3=CC=C(N4CCN(C)CC4)C=C3OC)=NC=C2Cl)=C1)=O

Appearance

White to beige 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

WZ4002 is one of three new compounds designed specifically to bind to and inhibit T790M-mutated EGFR. Importantly, WZ4002 does not inhibit wild-type EGFR; thus, it may have less effect on normal body cells and not cause diarrhea or rash like iressa and tarceva. WZ4002 is a compound that can inhibit T790M EGFR in the laboratory cells without inhibiting normal EGFR. Clinically effective doses could be safely reached in the mice. This new compound seems sufficiently promising in the lab to move on to phase I testing. However, as of August 2010, no news about clinical study was reported in the internet. Researchers tested WZ4002 in NSCLC cells with EGFR T90M and found several that were up to 100 times more potent than quinazolines in restricting cell growth. As an unexpected bonus, these compounds were nearly 100 times less powerful at slowing the growth of cells with normal EGFR, suggesting they would be less likely to produce side effects than current drugs. The agent which performed the best is the pyrimidine WZ4002. (source: http://lcins.org/2009/12/egfr-and-wz4002/).

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#TZC60301

QC Data

View QC data: current batch, Lot#TZC60301

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

WZ4002 is an EGFR inhibitor with IC50s of 2, 8, 3 and 2 nM for EGFRL858R, EGFRL858R/T790M, EGFRE746_A750 and EGFRE746_A750/T790M, respectively.

In vitro activity:

The ability of combination treatment with WZ4002 and SAHA to inhibit the proliferation of human NSCLC (non-small cell lung cancer) cells with an EGFR T790M mutation was investigated. While treatment with WZ4002 alone reduced the viability of PC-9G and H1975 cells in a small amount, combining it with SAHA resulted in significantly decreased cell viability for both cell lines (Fig. 1a, top panel). The combination of SAHA and WZ4002 manifested a synergistic effect on the viability of both PC-9G and H1975 cells in most combination concentrations (Fig. 1a, bottom panel). Reference: Int J Cancer. 2015 Jun 1;136(11):2717-29. https://onlinelibrary.wiley.com/doi/10.1002/ijc.29320

In vivo activity:

It was investigated whether combined treatment with SAHA and WZ4002 might show an enhanced anti-tumor effect on xenografts of H1975 cells in vivo. Following tumor formation, nude mice were treated with gefitinib (50 mg/kg), SAHA (25 mg/kg), or WZ4002 (25 mg/kg) alone or together with SAHA for 3 weeks. Monotherapy with gefitinib or WZ4002 resulted in only a marginal decrease in tumor volume, whereas treatment with the combination of WZ4002 and SAHA led to a marked shrinkage of tumor (Fig. 5a). Reference: Int J Cancer. 2015 Jun 1;136(11):2717-29. https://onlinelibrary.wiley.com/doi/10.1002/ijc.29320

	Solvent	mg/mL	mM
Solubility
	DMSO	54.3	109.76
	DMF	50.0	101.02
	Ethanol	1.0	2.02

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 494.97 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. Lee TG, Jeong EH, Kim SY, Kim HR, Kim CH. The combination of irreversible EGFR TKIs and SAHA induces apoptosis and autophagy-mediated cell death to overcome acquired resistance in EGFR T790M-mutated lung cancer. Int J Cancer. 2015 Jun 1;136(11):2717-29. doi: 10.1002/ijc.29320. Epub 2014 Nov 26. PMID: 25382705.

In vitro protocol:

In vivo protocol:

1: Ahmad I, Patel HM. Repurposing Non-Nucleosidic Reverse Transcriptase Inhibitors (NNRTIs) to Overcome EGFR T790M-Mediated Acquired Resistance in Non- Small Cell Lung Cancer. J Cell Biochem. 2025 Jan;126(1):e30653. doi: 10.1002/jcb.30653. Epub 2024 Sep 19. PMID: 39300843. 2: Kaynar A, Ozcan M, Li X, Turkez H, Zhang C, Uhlén M, Shoaie S, Mardinoglu A. Discovery of a Therapeutic Agent for Glioblastoma Using a Systems Biology-Based Drug Repositioning Approach. Int J Mol Sci. 2024 Jul 18;25(14):7868. doi: 10.3390/ijms25147868. PMID: 39063109; PMCID: PMC11277330. 3: Terlizzi C, De Rosa V, Iommelli F, Pezone A, Altobelli GG, Maddalena M, Dimitrov J, De Rosa C, Della Corte CM, Avvedimento VE, Del Vecchio S. ATM inhibition blocks glucose metabolism and amplifies the sensitivity of resistant lung cancer cell lines to oncogene driver inhibitors. Cancer Metab. 2023 Nov 6;11(1):20. doi: 10.1186/s40170-023-00320-4. PMID: 37932830; PMCID: PMC10629204. 4: De Rosa V, Iommelli F, Terlizzi C, Leggiero E, Camerlingo R, Altobelli GG, Fonti R, Pastore L, Del Vecchio S. Non-Canonical Role of PDK1 as a Negative Regulator of Apoptosis through Macromolecular Complexes Assembly at the ER- Mitochondria Interface in Oncogene-Driven NSCLC. Cancers (Basel). 2021 Aug 17;13(16):4133. doi: 10.3390/cancers13164133. PMID: 34439291; PMCID: PMC8391251. 5: Pawara R, Ahmad I, Nayak D, Wagh S, Wadkar A, Ansari A, Belamkar S, Surana S, Nath Kundu C, Patil C, Patel H. Novel, selective acrylamide linked quinazolines for the treatment of double mutant EGFR-L858R/T790M Non-Small-Cell lung cancer (NSCLC). Bioorg Chem. 2021 Oct;115:105234. doi: 10.1016/j.bioorg.2021.105234. Epub 2021 Aug 8. PMID: 34399322. 6: Ji W, Choi YJ, Kang MH, Sung KJ, Kim DH, Jung S, Choi CM, Lee JC, Rho JK. Efficacy of the CDK7 Inhibitor on EMT-Associated Resistance to 3rd Generation EGFR-TKIs in Non-Small Cell Lung Cancer Cell Lines. Cells. 2020 Dec 3;9(12):2596. doi: 10.3390/cells9122596. PMID: 33287368; PMCID: PMC7761809. 7: Hou W, Sun H, Ma Y, Liu C, Zhang Z. Identification and Optimization of Novel Cathepsin C Inhibitors Derived from EGFR Inhibitors. J Med Chem. 2019 Jun 27;62(12):5901-5919. doi: 10.1021/acs.jmedchem.9b00631. Epub 2019 Jun 17. PMID: 31145622. 8: Wintgens JP, Wichert SP, Popovic L, Rossner MJ, Wehr MC. Monitoring activities of receptor tyrosine kinases using a universal adapter in genetically encoded split TEV assays. Cell Mol Life Sci. 2019 Mar;76(6):1185-1199. doi: 10.1007/s00018-018-03003-2. Epub 2019 Jan 8. Erratum in: Cell Mol Life Sci. 2019 Oct;76(19):3915. doi: 10.1007/s00018-019-03244-9. PMID: 30623207; PMCID: PMC6675780. 9: Wan S, Yan R, Jiang Y, Li Z, Zhang J, Wu X. Insight into binding mechanisms of EGFR allosteric inhibitors using molecular dynamics simulations and free energy calculations. J Biomol Struct Dyn. 2019 Oct;37(16):4384-4394. doi: 10.1080/07391102.2018.1552197. Epub 2019 Jan 11. PMID: 30499387. 10: Kim S, Park AK, Cho J. Early emergence of de novo EGFR T790M gatekeeper mutations during erlotinib treatment in PC9 non-small cell lung cancer cells. Biochem Biophys Res Commun. 2018 Sep 5;503(2):710-714. doi: 10.1016/j.bbrc.2018.06.065. Epub 2018 Jun 27. PMID: 29909007. 11: Zhao P, Yao MY, Zhu SJ, Chen JY, Yun CH. Crystal structure of EGFR T790M/C797S/V948R in complex with EAI045. Biochem Biophys Res Commun. 2018 Jul 20;502(3):332-337. doi: 10.1016/j.bbrc.2018.05.154. PMID: 29802850. 12: Zhu SJ, Zhao P, Yang J, Ma R, Yan XE, Yang SY, Yang JW, Yun CH. Structural insights into drug development strategy targeting EGFR T790M/C797S. Oncotarget. 2018 Jan 10;9(17):13652-13665. doi: 10.18632/oncotarget.24113. PMID: 29568384; PMCID: PMC5862605. 13: Hou X, Du H, Quan X, Shi L, Zhang Q, Wu Y, Liu Y, Xiao J, Li Y, Lu L, Ai X, Zhan M, Yuan S, Sun L. Silibinin Inhibits NSCLC Metastasis by Targeting the EGFR/LOX Pathway. Front Pharmacol. 2018 Feb 8;9:21. doi: 10.3389/fphar.2018.00021. PMID: 29472856; PMCID: PMC5809401. 14: Lu X, Yu L, Zhang Z, Ren X, Smaill JB, Ding K. Targeting EGFRL858R/T790M and EGFRL858R/T790M/C797S resistance mutations in NSCLC: Current developments in medicinal chemistry. Med Res Rev. 2018 Sep;38(5):1550-1581. doi: 10.1002/med.21488. Epub 2018 Jan 26. PMID: 29377179. 15: Romu AA, Lei Z, Zhou B, Chen ZS, Korlipara V. Design, synthesis and biological evaluation of WZ4002 analogues as EGFR inhibitors. Bioorg Med Chem Lett. 2017 Nov 1;27(21):4832-4837. doi: 10.1016/j.bmcl.2017.09.048. Epub 2017 Sep 25. PMID: 28974338. 16: Joshi G, Nayyar H, Kalra S, Sharma P, Munshi A, Singh S, Kumar R. Pyrimidine containing epidermal growth factor receptor kinase inhibitors: Synthesis and biological evaluation. Chem Biol Drug Des. 2017 Nov;90(5):995-1006. doi: 10.1111/cbdd.13027. Epub 2017 Jul 12. PMID: 28544624. 17: Kong LL, Ma R, Yao MY, Yan XE, Zhu SJ, Zhao P, Yun CH. Structural pharmacological studies on EGFR T790M/C797S. Biochem Biophys Res Commun. 2017 Jun 24;488(2):266-272. doi: 10.1016/j.bbrc.2017.04.138. Epub 2017 Apr 26. PMID: 28456628. 18: De Rosa V, Iommelli F, Monti M, Mainolfi CG, Fonti R, Del Vecchio S. Early 18F-FDG uptake as a reliable imaging biomarker of T790M-mediated resistance but not MET amplification in non-small cell lung cancer treated with EGFR tyrosine kinase inhibitors. EJNMMI Res. 2016 Dec;6(1):74. doi: 10.1186/s13550-016-0229-0. Epub 2016 Oct 10. PMID: 27726115; PMCID: PMC5056924. 19: Wang A, Yan XE, Wu H, Wang W, Hu C, Chen C, Zhao Z, Zhao P, Li X, Wang L, Wang B, Ye Z, Wang J, Wang C, Zhang W, Gray NS, Weisberg EL, Chen L, Liu J, Yun CH, Liu Q. Ibrutinib targets mutant-EGFR kinase with a distinct binding conformation. Oncotarget. 2016 Oct 25;7(43):69760-69769. doi: 10.18632/oncotarget.11951. PMID: 27626175; PMCID: PMC5342513. 20: Xiao Q, Qu R, Gao D, Yan Q, Tong L, Zhang W, Ding J, Xie H, Li Y. Discovery of 5-(methylthio)pyrimidine derivatives as L858R/T790M mutant selective epidermal growth factor receptor (EGFR) inhibitors. Bioorg Med Chem. 2016 Jun 15;24(12):2673-80. doi: 10.1016/j.bmc.2016.04.032. Epub 2016 Apr 19. PMID: 27131639.