GW2974 | CAS#202272-68-2 | EGFR inhibitor

MedKoo Cat#: 341193 | Name: GW2974

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Description:

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

GW2974 is a Potent and selective dual inhibitor of EGFR. GW2974 was seen to have suppressed the protein expression of EGFR, inhibited cell proliferation, increased LDH activity, and induced apoptosis.

Chemical Structure

GW2974

CAS#202272-68-2

Theoretical Analysis

MedKoo Cat#: 341193

Name: GW2974

CAS#: 202272-68-2

Chemical Formula: C23H21N7

Exact Mass: 395.1858

Molecular Weight: 395.47

Elemental Analysis: C, 69.85; H, 5.35; N, 24.79

Price and Availability

Size	Price	Availability	Quantity
50mg	USD 575.00	2 Weeks

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Synonym

GW2974; GW-2974; GW 2974;

IUPAC/Chemical Name

N4-(1-Benzyl-1H-indazol-5-yl)-N6,N6-dimethyl-pyrido [3,4-d]pyrimidine-4,6-diamine

InChi Key

DYYZXRCFCVDSKD-UHFFFAOYSA-N

InChi Code

InChI=1S/C23H21N7/c1-29(2)22-11-19-20(13-24-22)25-15-26-23(19)28-18-8-9-21-17(10-18)12-27-30(21)14-16-6-4-3-5-7-16/h3-13,15H,14H2,1-2H3,(H,25,26,28)

SMILES Code

CN(C)C1=CC2=C(NC3=CC4=C(N(CC5=CC=CC=C5)N=C4)C=C3)N=CN=C2C=N1

Appearance

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

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

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#S22G01M17

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

GW2974 Potent and selective dual inhibitor of EGFR.

In vitro activity:

The specific EGFR inhibitor GW2974 effectively suppressed PMN phagocytosis induced by both EGF and THP, but not LPS (Figure 6C). Reference: Molecules. 2014 Jan 21;19(1):1328-43. https://pubmed.ncbi.nlm.nih.gov/24451252/

In vivo activity:

Thus, both wild-type mice and BK5.erbB2 mice were responsive to inhibition of tumor promotion by dietary administration of GW2974, although it produced a significantly greater inhibitory response in BK5.erbB2 mice. Reference: Cancer Prev Res (Phila). 2010 Aug;3(8):940-52. https://pubmed.ncbi.nlm.nih.gov/20682802/

Preparing Stock Solutions

The following data is based on the product molecular weight 395.47 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. Li KJ, Siao SC, Wu CH, Shen CY, Wu TH, Tsai CY, Hsieh SC, Yu CL. EGF receptor-dependent mechanism may be involved in the Tamm-Horsfall glycoprotein-enhanced PMN phagocytosis via activating Rho family and MAPK signaling pathway. Molecules. 2014 Jan 21;19(1):1328-43. doi: 10.3390/molecules19011328. PMID: 24451252; PMCID: PMC6271557. 2. Sodani K, Tiwari AK, Singh S, Patel A, Xiao ZJ, Chen JJ, Sun YL, Talele TT, Chen ZS. GW583340 and GW2974, human EGFR and HER-2 inhibitors, reverse ABCG2- and ABCB1-mediated drug resistance. Biochem Pharmacol. 2012 Jun 15;83(12):1613-22. doi: 10.1016/j.bcp.2012.02.028. Epub 2012 Mar 7. PMID: 22414725; PMCID: PMC3360928. 3. Kiguchi K, Kitamura T, Moore T, Rumi M, Chang HC, Treece D, Ruffino L, Connolly K, DiGiovanni J. Dual inhibition of both the epidermal growth factor receptor and erbB2 effectively inhibits the promotion of skin tumors during two-stage carcinogenesis. Cancer Prev Res (Phila). 2010 Aug;3(8):940-52. doi: 10.1158/1940-6207.CAPR-10-0010. Epub 2010 Aug 3. PMID: 20682802; PMCID: PMC2940063. 4. Sun Z, Sood S, Li N, Yang P, Newman RA, Yang CS, Chen X. Chemoprevention of 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamster cheek pouch by topical application of a dual inhibitor of epidermal growth factor receptor (EGFR) and ErbB2 tyrosine kinases. Oral Oncol. 2008 Jul;44(7):652-7. doi: 10.1016/j.oraloncology.2007.08.006. Epub 2007 Oct 23. PMID: 17936675; PMCID: PMC2546572.

In vitro protocol:

In vivo protocol:

1. Kiguchi K, Kitamura T, Moore T, Rumi M, Chang HC, Treece D, Ruffino L, Connolly K, DiGiovanni J. Dual inhibition of both the epidermal growth factor receptor and erbB2 effectively inhibits the promotion of skin tumors during two-stage carcinogenesis. Cancer Prev Res (Phila). 2010 Aug;3(8):940-52. doi: 10.1158/1940-6207.CAPR-10-0010. Epub 2010 Aug 3. PMID: 20682802; PMCID: PMC2940063. 2. Sun Z, Sood S, Li N, Yang P, Newman RA, Yang CS, Chen X. Chemoprevention of 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamster cheek pouch by topical application of a dual inhibitor of epidermal growth factor receptor (EGFR) and ErbB2 tyrosine kinases. Oral Oncol. 2008 Jul;44(7):652-7. doi: 10.1016/j.oraloncology.2007.08.006. Epub 2007 Oct 23. PMID: 17936675; PMCID: PMC2546572.

1: Salem AA, El Haty IA, Ghattas MA. GW-2974 and SCH-442416 modulators of tyrosine kinase and adenosine receptors can also stabilize human telomeric G-quadruplex DNA. PLoS One. 2022 Dec 7;17(12):e0277963. doi: 10.1371/journal.pone.0277963. PMID: 36476719; PMCID: PMC9728906. 2: Bao Z, Chen L, Guo S. Knockdown of SLC34A2 inhibits cell proliferation, metastasis, and elevates chemosensitivity in glioma. J Cell Biochem. 2019 Jun;120(6):10205-10214. doi: 10.1002/jcb.28305. Epub 2018 Dec 28. PMID: 30592329. 3: Wang X, Zeng J, Wang L, Zhang X, Liu Z, Zhang H, Dong J. Overexpression of microRNA-133b is associated with the increased survival of patients with hepatocellular carcinoma after curative hepatectomy: Involvement of the EGFR/PI3K/Akt/mTOR signaling pathway. Oncol Rep. 2017 Jul;38(1):141-150. doi: 10.3892/or.2017.5699. Epub 2017 Jun 6. PMID: 28586051. 4: Chakraborty AK, Mehra R, Digiovanna MP. Co-targeting ER and HER family receptors induces apoptosis in HER2-normal or overexpressing breast cancer models. Anticancer Res. 2015 Mar;35(3):1243-50. PMID: 25750271. 5: Li KJ, Siao SC, Wu CH, Shen CY, Wu TH, Tsai CY, Hsieh SC, Yu CL. EGF receptor-dependent mechanism may be involved in the Tamm-Horsfall glycoprotein- enhanced PMN phagocytosis via activating Rho family and MAPK signaling pathway. Molecules. 2014 Jan 21;19(1):1328-43. doi: 10.3390/molecules19011328. PMID: 24451252; PMCID: PMC6271557. 6: Wang L, Liu Q, Zhao H, Cui K, Yao L, Nie F, Jin G, Hao A, Wong ST. Differential effects of low- and high-dose GW2974, a dual epidermal growth factor receptor and HER2 kinase inhibitor, on glioblastoma multiforme invasion. J Neurosci Res. 2013 Jan;91(1):128-37. doi: 10.1002/jnr.23140. Epub 2012 Nov 1. PMID: 23115024. 7: Sodani K, Tiwari AK, Singh S, Patel A, Xiao ZJ, Chen JJ, Sun YL, Talele TT, Chen ZS. GW583340 and GW2974, human EGFR and HER-2 inhibitors, reverse ABCG2- and ABCB1-mediated drug resistance. Biochem Pharmacol. 2012 Jun 15;83(12):1613-22. doi: 10.1016/j.bcp.2012.02.028. Epub 2012 Mar 7. PMID: 22414725; PMCID: PMC3360928. 8: Xia W, Liu Z, Zong R, Liu L, Zhao S, Bacus SS, Mao Y, He J, Wulfkuhle JD, Petricoin EF 3rd, Osada T, Yang XY, Hartman ZC, Clay TM, Blackwell KL, Lyerly HK, Spector NL. Truncated ErbB2 expressed in tumor cell nuclei contributes to acquired therapeutic resistance to ErbB2 kinase inhibitors. Mol Cancer Ther. 2011 Aug;10(8):1367-74. doi: 10.1158/1535-7163.MCT-10-0991. Epub 2011 Jun 14. PMID: 21673090; PMCID: PMC3836594. 9: Rajabalian S, Hajializadeh Z, Pooraboli I, Jangi-Aghdam H, Badinloo M. Establishment, characterization, and drug sensitivity of a new Ewing sarcoma cell line (SS-ES-1). J Pediatr Hematol Oncol. 2010 Nov;32(8):e331-7. doi: 10.1097/MPH.0b013e3181ee4d16. Erratum in: J Pediatr Hematol Oncol. 2011 Apr;33(3):247. Badinloo, Marziyeh [added]. PMID: 20962673. 10: Kiguchi K, Kitamura T, Moore T, Rumi M, Chang HC, Treece D, Ruffino L, Connolly K, DiGiovanni J. Dual inhibition of both the epidermal growth factor receptor and erbB2 effectively inhibits the promotion of skin tumors during two- stage carcinogenesis. Cancer Prev Res (Phila). 2010 Aug;3(8):940-52. doi: 10.1158/1940-6207.CAPR-10-0010. Epub 2010 Aug 3. PMID: 20682802; PMCID: PMC2940063. 11: Terracciano D, Mazzarella C, Di Carlo A, Mariano A, Ferro M, Di Lorenzo G, Giordano A, Altieri V, De Placido S, Macchia V. Effects of the ErbB1/ErbB2 kinase inhibitor GW2974 on androgen-independent prostate cancer PC-3 cell line growth and NSE, chromogranin A and osteopontin content. Oncol Rep. 2010 Jul;24(1):213-7. doi: 10.3892/or_00000848. PMID: 20514464. 12: Wonders KY, Hydock DS, Greufe S, Schneider CM, Hayward R. Endurance exercise training preserves cardiac function in rats receiving doxorubicin and the HER-2 inhibitor GW2974. Cancer Chemother Pharmacol. 2009 Nov;64(6):1105-13. doi: 10.1007/s00280-009-0967-z. Epub 2009 Apr 8. PMID: 19352663. 13: Agarwal S, Zerillo C, Kolmakova J, Christensen JG, Harris LN, Rimm DL, Digiovanna MP, Stern DF. Association of constitutively activated hepatocyte growth factor receptor (Met) with resistance to a dual EGFR/Her2 inhibitor in non-small-cell lung cancer cells. Br J Cancer. 2009 Mar 24;100(6):941-9. doi: 10.1038/sj.bjc.6604937. Epub 2009 Feb 24. PMID: 19240716; PMCID: PMC2661782. 14: Shell SA, Lyass L, Trusk PB, Pry KJ, Wappel RL, Bacus SS. Activation of AMPK is necessary for killing cancer cells and sparing cardiac cells. Cell Cycle. 2008 Jun 15;7(12):1769-75. doi: 10.4161/cc.7.12.6016. Epub 2008 Jun 30. PMID: 18594201. 15: Lu J, Rho O, Wilker E, Beltran L, Digiovanni J. Activation of epidermal akt by diverse mouse skin tumor promoters. Mol Cancer Res. 2007 Dec;5(12):1342-52. doi: 10.1158/1541-7786.MCR-07-0115. PMID: 18171992. 16: Li P, Ge HB, Sun Z. [Inhibiting effects of GW2974 on DMBA-induced hamster buccal pouch carcinogenesis]. Zhonghua Kou Qiang Yi Xue Za Zhi. 2007 Jul;42(7):432-5. Chinese. PMID: 17961367. 17: Sun Z, Sood S, Li N, Yang P, Newman RA, Yang CS, Chen X. Chemoprevention of 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamster cheek pouch by topical application of a dual inhibitor of epidermal growth factor receptor (EGFR) and ErbB2 tyrosine kinases. Oral Oncol. 2008 Jul;44(7):652-7. doi: 10.1016/j.oraloncology.2007.08.006. Epub 2007 Oct 23. PMID: 17936675; PMCID: PMC2546572. 18: Spector NL, Yarden Y, Smith B, Lyass L, Trusk P, Pry K, Hill JE, Xia W, Seger R, Bacus SS. Activation of AMP-activated protein kinase by human EGF receptor 2/EGF receptor tyrosine kinase inhibitor protects cardiac cells. Proc Natl Acad Sci U S A. 2007 Jun 19;104(25):10607-12. doi: 10.1073/pnas.0701286104. Epub 2007 Jun 7. PMID: 17556544; PMCID: PMC1965560. 19: Witters LM, Witkoski A, Planas-Silva MD, Berger M, Viallet J, Lipton A. Synergistic inhibition of breast cancer cell lines with a dual inhibitor of EGFR-HER-2/neu and a Bcl-2 inhibitor. Oncol Rep. 2007 Feb;17(2):465-9. PMID: 17203189. 20: Coley HM, Shotton CF, Ajose-Adeogun A, Modjtahedi H, Thomas H. Receptor tyrosine kinase (RTK) inhibition is effective in chemosensitising EGFR- expressing drug resistant human ovarian cancer cell lines when used in combination with cytotoxic agents. Biochem Pharmacol. 2006 Oct 16;72(8):941-8. doi: 10.1016/j.bcp.2006.07.022. Epub 2006 Aug 24. PMID: 16934227.