TAE226 | NVP-TAE226 | CAS#761437-28 | FAK & IGF-IR Inhibitor

MedKoo Cat#: 406127 | Name: TAE226

Description:

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

TAE226 is a novel and potent ATP competitive inhibitor of FAK and IGF-IR with potential anticancer activity. TAE226 can block FAK and IGF-IR signaling pathways. TAE226 inhibited the phosphorylation of FAK as well as the downstream effectors AKT, extracellular signal-related kinase, and S6 ribosomal protein in multiple glioma cell lines. TAE226 induced a concentration-dependent decrease in cellular proliferation with an associated G(2) cell cycle arrest in every cell line and an increase in apoptosis in a cell-line-specific manner. TAE226 also decreased glioma cell adhesion, migration, and invasion through an artificial extracellular matrix.

Chemical Structure

TAE226

CAS#761437-28-9

Theoretical Analysis

MedKoo Cat#: 406127

Name: TAE226

CAS#: 761437-28-9

Chemical Formula: C23H25ClN6O3

Exact Mass: 468.1677

Molecular Weight: 468.94

Elemental Analysis: C, 58.91; H, 5.37; Cl, 7.56; N, 17.92; O, 10.24

Price and Availability

Size	Price	Availability
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,250.00	Ready to ship
500mg	USD 2,450.00	Ready to ship
1g	USD 3,650.00	Ready to ship

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Synonym

NVPTAE226, NVP TAE226, NVP-TAE226, TAE226, TAE226, TAE 226

IUPAC/Chemical Name

2-((5-chloro-2-((2-methoxy-4-morpholinophenyl)amino)pyrimidin-4-yl)amino)-N-methylbenzamide

InChi Key

UYJNQQDJUOUFQJ-UHFFFAOYSA-N

InChi Code

InChI=1S/C23H25ClN6O3/c1-25-22(31)16-5-3-4-6-18(16)27-21-17(24)14-26-23(29-21)28-19-8-7-15(13-20(19)32-2)30-9-11-33-12-10-30/h3-8,13-14H,9-12H2,1-2H3,(H,25,31)(H2,26,27,28,29)

SMILES Code

O=C(NC)C1=CC=CC=C1NC2=NC(NC3=CC=C(N4CCOCC4)C=C3OC)=NC=C2Cl

Appearance

White to light yellow 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

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#CRB50709

QC Data

View QC data: current batch, Lot#CRB50709

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

NVP-TAE 226 (TAE226) is a dual FAK and IGF-1R inhibitor with IC50s of 5.5 nM and 140 nM, respectively.

In vitro activity:

Then, the effect of TAE226 on phosphorylation of FAK, Akt and ERK1/2 was evaluated using 4T1 cells in vitro. Phosphorylation of FAK at Y397, Akt at S473 and ERK was observed in 4T1 cells (Fig. 2a). TAE226 inhibited phosphorylation of FAK at Y397, resulting in suppression of phosphorylation of Akt at S473 and ERK1/2 in 4T1 cells 1 h after treatment (Fig. 2a). Reference: BMC Res Notes. 2019 Jun 18;12(1):347. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6582604/

In vivo activity:

Anti-tumor activity of TAE226 was evaluated in the MIA PaCa-2 subcutaneous and orthotopic xenograft models. Oral administration of TAE226 efficiently inhibited MIA PaCa-2 tumor growth at all doses tested. After 14 days treatment, T/C values were 50% at 10 mg/kg and 13% at 30 mg/kg, qd for 7×/week (Fig. 1c, Table S2). At a dose of 100 mg/kg, qd for 5×/week, tumor regression (17%) was observed (Fig. 1c). TAE226 also inhibited MIA PaCa-2 orthotopic tumor growth in pancreas dose-dependently (Fig. 1d). Reference: BMC Res Notes. 2019 Jun 18;12(1):347. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6582604/

	Solvent	mg/mL	mM
Solubility
	DMSO	51.3	109.46
	DMF	30.0	63.97
	DMF:PBS (pH 7.2) (1:1)	0.5	1.07

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 468.94 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. Fukami S, Tomioka D, Murakami Y, Honda T, Hatakeyama S. Pharmacological profiling of a dual FAK/IGF-1R kinase inhibitor TAE226 in cellular and in vivo tumor models. BMC Res Notes. 2019 Jun 18;12(1):347. doi: 10.1186/s13104-019-4389-7. PMID: 31215459; PMCID: PMC6582604. 2. Moritake H, Saito Y, Sawa D, Sameshima N, Yamada A, Kinoshita M, Kamimura S, Konomoto T, Nunoi H. TAE226, a dual inhibitor of focal adhesion kinase and insulin-like growth factor-I receptor, is effective for Ewing sarcoma. Cancer Med. 2019 Dec;8(18):7809-7821. doi: 10.1002/cam4.2647. Epub 2019 Nov 6. PMID: 31692287; PMCID: PMC6912025.

In vitro protocol:

In vivo protocol:

1: Shi Q, Hjelmeland AB, Keir ST, Song L, Wickman S, Jackson D, Ohmori O, Bigner DD, Friedman HS, Rich JN. A novel low-molecular weight inhibitor of focal adhesion kinase, TAE226, inhibits glioma growth. Mol Carcinog. 2007 Jun;46(6):488-96. doi: 10.1002/mc.20297. PMID: 17219439. 2: Liu TJ, LaFortune T, Honda T, Ohmori O, Hatakeyama S, Meyer T, Jackson D, de Groot J, Yung WK. Inhibition of both focal adhesion kinase and insulin-like growth factor-I receptor kinase suppresses glioma proliferation in vitro and in vivo. Mol Cancer Ther. 2007 Apr;6(4):1357-67. doi: 10.1158/1535-7163.MCT-06-0476. PMID: 17431114. 3: Golubovskaya VM, Virnig C, Cance WG. TAE226-induced apoptosis in breast cancer cells with overexpressed Src or EGFR. Mol Carcinog. 2008 Mar;47(3):222-34. doi: 10.1002/mc.20380. PMID: 17849451. 4: Halder J, Lin YG, Merritt WM, Spannuth WA, Nick AM, Honda T, Kamat AA, Han LY, Kim TJ, Lu C, Tari AM, Bornmann W, Fernandez A, Lopez-Berestein G, Sood AK. Therapeutic efficacy of a novel focal adhesion kinase inhibitor TAE226 in ovarian carcinoma. Cancer Res. 2007 Nov 15;67(22):10976-83. doi: 10.1158/0008-5472.CAN-07-2667. Erratum in: Cancer Res. 2018 Jul 15;78(14):4100. doi: 10.1158/0008-5472.CAN-18-1307. PMID: 18006843. 5: Beierle EA, Trujillo A, Nagaram A, Golubovskaya VM, Cance WG, Kurenova EV. TAE226 inhibits human neuroblastoma cell survival. Cancer Invest. 2008 Mar;26(2):145-51. doi: 10.1080/07357900701577475. PMID: 18259944. 6: Watanabe N, Takaoka M, Sakurama K, Tomono Y, Hatakeyama S, Ohmori O, Motoki T, Shirakawa Y, Yamatsuji T, Haisa M, Matsuoka J, Beer DG, Nagatsuka H, Tanaka N, Naomoto Y. Dual tyrosine kinase inhibitor for focal adhesion kinase and insulin-like growth factor-I receptor exhibits anticancer effect in esophageal adenocarcinoma in vitro and in vivo. Clin Cancer Res. 2008 Jul 15;14(14):4631-9. doi: 10.1158/1078-0432.CCR-07-4755. PMID: 18628478. 7: Golubovskaya VM, Nyberg C, Zheng M, Kweh F, Magis A, Ostrov D, Cance WG. A small molecule inhibitor, 1,2,4,5-benzenetetraamine tetrahydrochloride, targeting the y397 site of focal adhesion kinase decreases tumor growth. J Med Chem. 2008 Dec 11;51(23):7405-16. doi: 10.1021/jm800483v. PMID: 18989950; PMCID: PMC2662449. 8: Wang ZG, Fukazawa T, Nishikawa T, Watanabe N, Sakurama K, Motoki T, Takaoka M, Hatakeyama S, Omori O, Ohara T, Tanabe S, Fujiwara Y, Shirakawa Y, Yamatsuji T, Tanaka N, Naomoto Y. TAE226, a dual inhibitor for FAK and IGF-IR, has inhibitory effects on mTOR signaling in esophageal cancer cells. Oncol Rep. 2008 Dec;20(6):1473-7. PMID: 19020730. 9: Lietha D, Eck MJ. Crystal structures of the FAK kinase in complex with TAE226 and related bis-anilino pyrimidine inhibitors reveal a helical DFG conformation. PLoS One. 2008;3(11):e3800. doi: 10.1371/journal.pone.0003800. Epub 2008 Nov 24. PMID: 19030106; PMCID: PMC2582962. 10: Sakurama K, Noma K, Takaoka M, Tomono Y, Watanabe N, Hatakeyama S, Ohmori O, Hirota S, Motoki T, Shirakawa Y, Yamatsuji T, Haisa M, Matsuoka J, Tanaka N, Naomoto Y. Inhibition of focal adhesion kinase as a potential therapeutic strategy for imatinib-resistant gastrointestinal stromal tumor. Mol Cancer Ther. 2009 Jan;8(1):127-34. doi: 10.1158/1535-7163.MCT-08-0884. PMID: 19139121. 11: Mansell JP, Farrar D, Jones S, Nowghani M. Cytoskeletal reorganisation, 1alpha,25-dihydroxy vitamin D3 and human MG63 osteoblast maturation. Mol Cell Endocrinol. 2009 Jun 16;305(1-2):38-46. doi: 10.1016/j.mce.2009.02.032. Epub 2009 Mar 14. PMID: 19433260. 12: Hehlgans S, Lange I, Eke I, Cordes N. 3D cell cultures of human head and neck squamous cell carcinoma cells are radiosensitized by the focal adhesion kinase inhibitor TAE226. Radiother Oncol. 2009 Sep;92(3):371-8. doi: 10.1016/j.radonc.2009.08.001. Epub 2009 Sep 2. PMID: 19729215. 13: Schultze A, Decker S, Otten J, Horst AK, Vohwinkel G, Schuch G, Bokemeyer C, Loges S, Fiedler W. TAE226-mediated inhibition of focal adhesion kinase interferes with tumor angiogenesis and vasculogenesis. Invest New Drugs. 2010 Dec;28(6):825-33. doi: 10.1007/s10637-009-9326-5. Epub 2009 Sep 26. PMID: 19784551. 14: Abban CY, Meneses PI. Usage of heparan sulfate, integrins, and FAK in HPV16 infection. Virology. 2010 Jul 20;403(1):1-16. doi: 10.1016/j.virol.2010.04.007. Epub 2010 May 2. PMID: 20441998; PMCID: PMC2883642. 15: Kurio N, Shimo T, Fukazawa T, Takaoka M, Okui T, Hassan NM, Honami T, Hatakeyama S, Ikeda M, Naomoto Y, Sasaki A. Anti-tumor effect in human breast cancer by TAE226, a dual inhibitor for FAK and IGF-IR in vitro and in vivo. Exp Cell Res. 2011 May 1;317(8):1134-46. doi: 10.1016/j.yexcr.2011.02.008. Epub 2011 Feb 19. PMID: 21338601. 16: Bhavaraju K, Lakhani PR, Dorsam RT, Jin J, Hitchcock IS, Sanjay A, Kunapuli SP. G(12/13) signaling pathways substitute for integrin αIIbβ3-signaling for thromboxane generation in platelets. PLoS One. 2011 Feb 10;6(2):e16586. doi: 10.1371/journal.pone.0016586. PMID: 21347357; PMCID: PMC3037367. 17: Plaza-Menacho I, Morandi A, Mologni L, Boender P, Gambacorti-Passerini C, Magee AI, Hofstra RM, Knowles P, McDonald NQ, Isacke CM. Focal adhesion kinase (FAK) binds RET kinase via its FERM domain, priming a direct and reciprocal RET- FAK transactivation mechanism. J Biol Chem. 2011 May 13;286(19):17292-302. doi: 10.1074/jbc.M110.168500. Epub 2011 Mar 22. PMID: 21454698; PMCID: PMC3089571. 18: Eke I, Cordes N. Dual targeting of EGFR and focal adhesion kinase in 3D grown HNSCC cell cultures. Radiother Oncol. 2011 Jun;99(3):279-86. doi: 10.1016/j.radonc.2011.06.006. Epub 2011 Jun 23. PMID: 21704406. 19: Golubovskaya VM, Ho B, Zheng M, Magis A, Ostrov D, Cance WG. Mitoxantrone targets the ATP-binding site of FAK, binds the FAK kinase domain and decreases FAK, Pyk-2, c-Src, and IGF-1R in vitro kinase activities. Anticancer Agents Med Chem. 2013 May;13(4):546-54. doi: 10.2174/1871520611313040003. PMID: 22292772; PMCID: PMC3625494. 20: Hao HF, Takaoka M, Bao XH, Wang ZG, Tomono Y, Sakurama K, Ohara T, Fukazawa T, Yamatsuji T, Fujiwara T, Naomoto Y. Oral administration of FAK inhibitor TAE226 inhibits the progression of peritoneal dissemination of colorectal cancer. Biochem Biophys Res Commun. 2012 Jul 13;423(4):744-9. doi: 10.1016/j.bbrc.2012.06.030. Epub 2012 Jun 13. PMID: 22705303.