WZ4002
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    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 203170

CAS#: 1213269-23-8

Description: 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

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WZ4002
CAS# 1213269-23-8
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 203170
Name: WZ4002
CAS#: 1213269-23-8
Chemical Formula: C25H27ClN6O3
Exact Mass: 494.18
Molecular Weight: 494.970
Elemental Analysis: C, 60.66; H, 5.50; Cl, 7.16; N, 16.98; O, 9.70

Price and Availability

Size Price Availability Quantity
10mg USD 90 Ready to ship
25mg USD 150 Ready to ship
50mg USD 250 Ready to ship
100mg USD 425 Ready to ship
200mg USD 750 Ready to ship
500mg USD 1250 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/).        

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

Solubility Data

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

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.

Recalculate based on batch purity %
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: 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 vivo 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.

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