ALW-II-41-27
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MedKoo CAT#: 407852

CAS#: 1186206-79-0

Description: 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

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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: 607.6962
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
5.0mg USD 300.0 2 Weeks
25.0mg USD 750.0 2 Weeks
50.0mg USD 1350.0 2 Weeks
Bulk inquiry

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

Product Data:

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.

Solubility Data

Solvent Max Conc. mg/mL Max Conc. 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

Preparing Stock Solutions

The following data is based on the product molecular weight 607.6962 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: 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: 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 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.

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1: 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. PubMed PMID: 28581527; PubMed Central PMCID: PMC5629103.

2: 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. PubMed. PMID: 26744526; PubMed Central PMCID: PMC4715957.

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. eCollection 2015. PubMed PMID: 26046350; PubMed Central PMCID: PMC4457528.

4: 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. PubMed PMID: 24713656; PubMed Central PMCID: PMC4001547.

5: 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. PubMed PMID: 19553108; PubMed Central PMCID: PMC2730633.



Additional Information

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