ALW-II-41-27 | CAS#1186206-79-0 | Eph receptor tyrosine kinase inhibitor

MedKoo Cat#: 407852 | Name: ALW-II-41-27

Description:

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

ALW-II-41-27 is a Eph receptor tyrosine kinase inhibitor. pharmacologic inhibition of EPHA2 by the small-molecule inhibitor ALW-II-41-27 decreased both survival and proliferation of erlotinib-resistant tumor cells and inhibited tumor growth in vivo. ALW-II-41-27 was also effective in decreasing viability of cells with acquired resistance to the third-generation EGFR TKI AZD9291. Collectively, these data define a role for EPHA2 in the maintenance of cell survival of TKI-resistant, EGFR-mutant lung cancer and indicate that EPHA2 may serve as a useful therapeutic target in TKI-resistant tumors.

Chemical Structure

ALW-II-41-27

CAS#1186206-79-0

Theoretical Analysis

MedKoo Cat#: 407852

Name: ALW-II-41-27

CAS#: 1186206-79-0

Chemical Formula: C32H32F3N5O2S

Exact Mass: 607.2229

Molecular Weight: 607.70

Elemental Analysis: C, 63.25; H, 5.31; F, 9.38; N, 11.52; O, 5.27; S, 5.28

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 350.00	2 Weeks
25mg	USD 850.00	2 Weeks

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Synonym

ALW-II-41-27; ALW II-41-27; ALWII-41-27; ALW-II-4127; ALW II-4127; ALWII-4127.

IUPAC/Chemical Name

N-(5-((4-((4-ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)carbamoyl)-2-methylphenyl)-5-(thiophen-2-yl)nicotinamide

InChi Key

HYWXBDQAYLPMIX-UHFFFAOYSA-N

InChi Code

InChI=1S/C32H32F3N5O2S/c1-3-39-10-12-40(13-11-39)20-23-8-9-26(17-27(23)32(33,34)35)37-30(41)22-7-6-21(2)28(16-22)38-31(42)25-15-24(18-36-19-25)29-5-4-14-43-29/h4-9,14-19H,3,10-13,20H2,1-2H3,(H,37,41)(H,38,42)

SMILES Code

O=C(NC1=CC(C(NC2=CC=C(CN3CCN(CC)CC3)C(C(F)(F)F)=C2)=O)=CC=C1C)C4=CN=CC(C5=CC=CS5)=C4

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

The Eph family of receptor tyrosine kinases has drawn growing attention due to their role in regulating diverse biological phenomena.

Product Data

Product Data

Instruction

View handling instruction

Biological target:

Eph receptor tyrosine kinase inhibitor.

In vitro activity:

The development of a novel therapeutic strategy for SCLC has become a pressing issue. It was found that expression of Eph receptor A2 (EphA2) is upregulated in three of 13 SCLC cell lines and five of 76 SCLC tumor samples. Genetic inhibition using siRNA of EphA2 significantly suppressed the cellular proliferation via induction of cell cycle arrest in SBC-5 cells. Furthermore, small molecule inhibitors of EphA2 (ALW-II-41-27 and dasatinib) also exclusively inhibited proliferation of EphA2-positive SCLC cells by the same mechanism. Collectively, EphA2 could be a promising candidate as a therapeutic target for SCLC. Refernce: Ishigaki H, Minami T, Morimura O, Kitai H, Horio D, Koda Y, Fujimoto E, Negi Y, Nakajima Y, Niki M, Kanemura S, Shibata E, Mikami K, Takahashi R, Yokoi T, Kuribayashi K, Kijima T. EphA2 inhibition suppresses proliferation of small-cell lung cancer cells through inducing cell cycle arrest. Biochem Biophys Res Commun. 2019 Nov 19;519(4):846-853. doi: 10.1016/j.bbrc.2019.09.076. Epub 2019 Sep 24. PMID: 31558317.

In vivo activity:

In the present study, it was shown that ALW-II-41-27 decreased gastrointestinal motility and abdominal withdrawal reflex (AWR) scores, markedly reduced the levels of oxidative stress markers [4-hydroxy-2-nonenal (4-HNE), protein carbonyl, and 8-hydroxy-2-de-axyguanine (8-OHdG)] and proinflammatory cytokines (TNF-α, IL-6, IL-17, and ICAM-1), and remarkably increased the level of anti-inflammatory cytokine (IL-10) in serum and colon of Trichinella spiralis-infected mice. Moreover, ALW-II-41-27 was effective in suppressing oxidative stress and inflammation in LPS-treated NCM460 colonic cells. Treatment of ALW-II-41-27 reversed the activation of NF-κB and inactivation of Nrf2 in LPS-treated NCM460 cells. Importantly, these protective effects of ALW-II-41-27 were partially inhibited by EphA2 KO and abolished by EphA2 overexpression. In conclusion, EphA2 may represent a promising therapeutic target for patients with PI-IBS and ALW-II-41-27 might function as a novel therapeutic agent for PI-IBS. Reference: Zeng L, Li K, Wei H, Hu J, Jiao L, Yu S, Xiong Y. A Novel EphA2 Inhibitor Exerts Beneficial Effects in PI-IBS in Vivo and in Vitro Models via Nrf2 and NF-κB Signaling Pathways. Front Pharmacol. 2018 Mar 27;9:272. doi: 10.3389/fphar.2018.00272. PMID: 29662452; PMCID: PMC5890185.

	Solvent	mg/mL	mM
Solubility
	DMSO	10.0	16.46
	DMSO:PBS (pH 7.2) (1:1)	0.5	0.82
	DMF	10.0	16.46
	Ethanol	0.5	0.82

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 607.70 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:

Ishigaki H, Minami T, Morimura O, Kitai H, Horio D, Koda Y, Fujimoto E, Negi Y, Nakajima Y, Niki M, Kanemura S, Shibata E, Mikami K, Takahashi R, Yokoi T, Kuribayashi K, Kijima T. EphA2 inhibition suppresses proliferation of small-cell lung cancer cells through inducing cell cycle arrest. Biochem Biophys Res Commun. 2019 Nov 19;519(4):846-853. doi: 10.1016/j.bbrc.2019.09.076. Epub 2019 Sep 24. PMID: 31558317.

In vitro protocol:

In vivo protocol:

Zeng L, Li K, Wei H, Hu J, Jiao L, Yu S, Xiong Y. A Novel EphA2 Inhibitor Exerts Beneficial Effects in PI-IBS in Vivo and in Vitro Models via Nrf2 and NF-κB Signaling Pathways. Front Pharmacol. 2018 Mar 27;9:272. doi: 10.3389/fphar.2018.00272. PMID: 29662452; PMCID: PMC5890185.

1: Li X, Li D, Ma R. ALW-II-41-27, an EphA2 inhibitor, inhibits proliferation, migration and invasion of cervical cancer cells via inhibition of the RhoA/ROCK pathway. Oncol Lett. 2022 Apr;23(4):129. doi: 10.3892/ol.2022.13249. Epub 2022 Feb 18. PMID: 35251349; PMCID: PMC8895465. 2: Zeng L, Li K, Wei H, Hu J, Jiao L, Yu S, Xiong Y. A Novel EphA2 Inhibitor Exerts Beneficial Effects in PI-IBS in Vivo and in Vitro Models via Nrf2 and NF-κB Signaling Pathways. Front Pharmacol. 2018 Mar 27;9:272. doi: 10.3389/fphar.2018.00272. PMID: 29662452; PMCID: PMC5890185. 3: Moccia M, Liu Q, Guida T, Federico G, Brescia A, Zhao Z, Choi HG, Deng X, Tan L, Wang J, Billaud M, Gray NS, Carlomagno F, Santoro M. Identification of Novel Small Molecule Inhibitors of Oncogenic RET Kinase. PLoS One. 2015 Jun 5;10(6):e0128364. doi: 10.1371/journal.pone.0128364. PMID: 26046350; PMCID: PMC4457528. 4: Xiang YP, Xiao T, Li QG, Lu SS, Zhu W, Liu YY, Qiu JY, Song ZH, Huang W, Yi H, Tang YY, Xiao ZQ. Y772 phosphorylation of EphA2 is responsible for EphA2-dependent NPC nasopharyngeal carcinoma growth by Shp2/Erk-1/2 signaling pathway. Cell Death Dis. 2020 Aug 27;11(8):709. doi: 10.1038/s41419-020-02831-0. PMID: 32848131; PMCID: PMC7449971. 5: Furukawa T, Kimura H, Torimoto H, Yagi Y, Kawashima H, Arimitsu K, Yasui H. A Putative Single-Photon Emission CT Imaging Tracer for Erythropoietin-Producing Hepatocellular A2 Receptor. ACS Med Chem Lett. 2021 Jul 14;12(8):1238-1244. doi: 10.1021/acsmedchemlett.1c00030. PMID: 34413953; PMCID: PMC8365995. 6: Shen L, Li Z, Shen L. Quantitative Tyrosine Phosphoproteomic Analysis of Resistance to Radiotherapy in Nasopharyngeal Carcinoma Cells. Cancer Manag Res. 2020 Dec 9;12:12667-12678. doi: 10.2147/CMAR.S260028. PMID: 33328764; PMCID: PMC7733897. 7: Prakash PS, Kruse A, Vogel C, Schagdarsurengin U, Wagenlehner F. Targeting Host Tyrosine Kinase Receptor EPHA2 Signaling Affects Uropathogen Infection in Human Bladder Epithelial Cells. Pathogens. 2022 Oct 12;11(10):1176. doi: 10.3390/pathogens11101176. PMID: 36297233; PMCID: PMC9607038. 8: Martini G, Cardone C, Vitiello PP, Belli V, Napolitano S, Troiani T, Ciardiello D, Della Corte CM, Morgillo F, Matrone N, Sforza V, Papaccio G, Desiderio V, Paul MC, Moreno-Viedma V, Normanno N, Rachiglio AM, Tirino V, Maiello E, Latiano TP, Rizzi D, Signoriello G, Sibilia M, Ciardiello F, Martinelli E. EPHA2 Is a Predictive Biomarker of Resistance and a Potential Therapeutic Target for Improving Antiepidermal Growth Factor Receptor Therapy in Colorectal Cancer. Mol Cancer Ther. 2019 Apr;18(4):845-855. doi: 10.1158/1535-7163.MCT-18-0539. Epub 2019 Mar 1. PMID: 30824612. 9: Ishigaki H, Minami T, Morimura O, Kitai H, Horio D, Koda Y, Fujimoto E, Negi Y, Nakajima Y, Niki M, Kanemura S, Shibata E, Mikami K, Takahashi R, Yokoi T, Kuribayashi K, Kijima T. EphA2 inhibition suppresses proliferation of small-cell lung cancer cells through inducing cell cycle arrest. Biochem Biophys Res Commun. 2019 Nov 19;519(4):846-853. doi: 10.1016/j.bbrc.2019.09.076. Epub 2019 Sep 24. PMID: 31558317. 10: Amato KR, Wang S, Tan L, Hastings AK, Song W, Lovly CM, Meador CB, Ye F, Lu P, Balko JM, Colvin DC, Cates JM, Pao W, Gray NS, Chen J. EPHA2 Blockade Overcomes Acquired Resistance to EGFR Kinase Inhibitors in Lung Cancer. Cancer Res. 2016 Jan 15;76(2):305-18. doi: 10.1158/0008-5472.CAN-15-0717. Epub 2016 Jan 7. PMID: 26744526; PMCID: PMC4715957. 11: Amato KR, Wang S, Hastings AK, Youngblood VM, Santapuram PR, Chen H, Cates JM, Colvin DC, Ye F, Brantley-Sieders DM, Cook RS, Tan L, Gray NS, Chen J. Genetic and pharmacologic inhibition of EPHA2 promotes apoptosis in NSCLC. J Clin Invest. 2014 May;124(5):2037-49. doi: 10.1172/JCI72522. Epub 2014 Apr 8. PMID: 24713656; PMCID: PMC4001547. 12: Hudecek R, Kohlova B, Siskova I, Piskacek M, Knight A. Blocking of EphA2 on Endometrial Tumor Cells Reduces Susceptibility to Vδ1 Gamma-Delta T-Cell- Mediated Killing. Front Immunol. 2021 Oct 7;12:752646. doi: 10.3389/fimmu.2021.752646. PMID: 34691070; PMCID: PMC8529280. 13: Zhao P, Sun J, Huang X, Zhang X, Liu X, Liu R, Du G, Gan W, Yang C, Tang Y, Chen C, Jiang D. Targeting the KLF5-EphA2 axis can restrain cancer stemness and overcome chemoresistance in basal-like breast cancer. Int J Biol Sci. 2023 Mar 21;19(6):1861-1874. doi: 10.7150/ijbs.82567. PMID: 37063424; PMCID: PMC10092769. 14: Zhang T, Li J, Ma X, Yang Y, Sun W, Jin W, Wang L, He Y, Yang F, Yi Z, Hua Y, Liu M, Chen Y, Cai Z. Inhibition of HDACs-EphA2 Signaling Axis with WW437 Demonstrates Promising Preclinical Antitumor Activity in Breast Cancer. EBioMedicine. 2018 May;31:276-286. doi: 10.1016/j.ebiom.2018.05.003. Erratum in: EBioMedicine. 2020 Feb;52:102629. PMID: 29759486; PMCID: PMC6013969. 15: Hong HN, Won YJ, Shim JH, Kim HJ, Han SH, Kim BS, Kim HS. Cancer-associated fibroblasts promote gastric tumorigenesis through EphA2 activation in a ligand- independent manner. J Cancer Res Clin Oncol. 2018 Sep;144(9):1649-1663. doi: 10.1007/s00432-018-2683-8. Epub 2018 Jun 12. PMID: 29948146. 16: Ruan H, Li S, Bao L, Zhang X. Enhanced YB1/EphA2 axis signaling promotes acquired resistance to sunitinib and metastatic potential in renal cell carcinoma. Oncogene. 2020 Sep;39(38):6113-6128. doi: 10.1038/s41388-020-01409-6. Epub 2020 Aug 19. Erratum in: Oncogene. 2023 Jan;42(2):165-167. PMID: 32814829; PMCID: PMC7498371. 17: Giordano G, Merlini A, Ferrero G, Mesiano G, Fiorino E, Brusco S, Centomo ML, Leuci V, D'Ambrosio L, Aglietta M, Sangiolo D, Grignani G, Pignochino Y. EphA2 Expression in Bone Sarcomas: Bioinformatic Analyses and Preclinical Characterization in Patient-Derived Models of Osteosarcoma, Ewing's Sarcoma and Chondrosarcoma. Cells. 2021 Oct 26;10(11):2893. doi: 10.3390/cells10112893. PMID: 34831119; PMCID: PMC8616526. 18: Wang H, Hou W, Perera A, Bettler C, Beach JR, Ding X, Li J, Denning MF, Dhanarajan A, Cotler SJ, Joyce C, Yin J, Ahmed F, Roberts LR, Qiu W. Targeting EphA2 suppresses hepatocellular carcinoma initiation and progression by dual inhibition of JAK1/STAT3 and AKT signaling. Cell Rep. 2021 Feb 23;34(8):108765. doi: 10.1016/j.celrep.2021.108765. PMID: 33626345; PMCID: PMC7954228. 19: Song W, Hwang Y, Youngblood VM, Cook RS, Balko JM, Chen J, Brantley-Sieders DM. Targeting EphA2 impairs cell cycle progression and growth of basal- like/triple-negative breast cancers. Oncogene. 2017 Oct 5;36(40):5620-5630. doi: 10.1038/onc.2017.170. Epub 2017 Jun 5. PMID: 28581527; PMCID: PMC5629103. 20: Choi Y, Syeda F, Walker JR, Finerty PJ Jr, Cuerrier D, Wojciechowski A, Liu Q, Dhe-Paganon S, Gray NS. Discovery and structural analysis of Eph receptor tyrosine kinase inhibitors. Bioorg Med Chem Lett. 2009 Aug 1;19(15):4467-70. doi: 10.1016/j.bmcl.2009.05.029. Epub 2009 May 13. PMID: 19553108; PMCID: PMC2730633.