EAI045
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    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 406836

CAS#: 1942114-09-1

Description: EAI045 ia a potent and selective EGFR inhbitor. EAI045 targets selected drug-resistant EGFR mutants but spares the wild-type receptor. EAI045 inhibits L858R/T790M-mutant EGFR with low-nanomolar potency in biochemical assays.


Chemical Structure

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EAI045
CAS# 1942114-09-1

Theoretical Analysis

MedKoo Cat#: 406836
Name: EAI045
CAS#: 1942114-09-1
Chemical Formula: C19H14FN3O3S
Exact Mass: 383.07
Molecular Weight: 383.397
Elemental Analysis: C, 59.52; H, 3.68; F, 4.96; N, 10.96; O, 12.52; S, 8.36

Price and Availability

Size Price Availability Quantity
10mg USD 90 Ready to ship
25mg USD 150 Ready to ship
50mg USD 225 Ready to ship
100mg USD 350 Ready to ship
200mg USD 550 Ready to ship
500mg USD 950 Ready to ship
1g USD 1750 2 weeks
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Related CAS #: 1942114-09-1,  

Synonym: EAI045; EAI-045; EAI 045.

IUPAC/Chemical Name: 2-(5-fluoro-2-hydroxyphenyl)-2-(3-oxo-1H-isoindol-2-yl)-N-(1,3-thiazol-2-yl)acetamide

InChi Key: YTUFHOKUFOQRDF-UHFFFAOYSA-N

InChi Code: InChI=1S/C19H14FN3O3S/c20-12-5-6-15(24)14(9-12)16(17(25)22-19-21-7-8-27-19)23-10-11-3-1-2-4-13(11)18(23)26/h1-9,16,24H,10H2,(H,21,22,25)

SMILES Code: O=C(NC1=NC=CS1)C(C2=CC(F)=CC=C2O)N3CC4=C(C=CC=C4)C3=O

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:

Biological target: EAI045 is an allosteric and the fourth-generation inhibitor of mutant EGFR with IC50s of 1.9, 0.019, 0.19 and 0.002 μM for EGFR, EGFRL858R, EGFRT790M and EGFRL858R/T790M at 10 μM ATP, respectively.
In vitro activity: In L858R/T790M-mutant NSCLC cell line H1975 cells, EAI045 decreased but did not completely abolish the EGFR auto-phosphorylation. In stably transfected NIH-3T3 cells harboring the L858R/T790M EGFR mutant, EAI045 showed the same activity. In L858R-mutant H3255 cells, EAI045 exhibited moderate activity. In the HaCaT cells, a keratinocyte cell line with wild-type EGFR, EAI045 did not show any activity of inhibiting EGFR phosphorylation. These again confirmed the selectivity of EAI045 for mutant EGFR. Since dimerization of EGFR is required for its activation, these investigators hypothesized that the allosteric inhibitor was inactive for those asymmetric dimers/dimers between wild-type and mutant EGFR peptides. The investigators confirmed that EAI045 was markedly more active in dimerization-defective EGFR mutants. When combined with cetuximab, a monoclonal antibody that can block EGFR dimerization by preventing EGF ligand binding, EAI045 markedly inhibited the proliferation of Ba/F3 cells bearing L858R/T790M mutation. These in vitro studies proved that EAI045 is active and selective for T790M- harboring EGFR mutants that are in a monomer state. Reference: Cancer Lett. 2017 Jan 28;385:51-54. https://linkinghub.elsevier.com/retrieve/pii/S0304-3835(16)30686-3
In vivo activity: In a genetically engineered mouse model of L858R/T790M-mutant-driven lung cancer, the efficacy of EAI045 was tested alone and in combination with cetuximab. Remarkable tumor regression was observed in L858R/T790M-mutant mice treated with the combination of EAI045 and cetuximab. No response was seen in those mice treated with EAI045 alone. The same effect was seen in both L858R/T790M/C797S- engineered Ba/F3 cells and in mice carrying the L858R/T790M/C797S tumor xenografts. These assays clearly showed that EAI045 can overcome resistance from acquired T790M and C797S mutations. Reference: Cancer Lett. 2017 Jan 28;385:51-54. https://linkinghub.elsevier.com/retrieve/pii/S0304-3835(16)30686-3

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 76.0 198.23

Preparing Stock Solutions

The following data is based on the product molecular weight 383.40 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:
In vitro protocol: 1. Wang S, Song Y, Liu D. EAI045: The fourth-generation EGFR inhibitor overcoming T790M and C797S resistance. Cancer Lett. 2017 Jan 28;385:51-54. doi: 10.1016/j.canlet.2016.11.008. Epub 2016 Nov 10. PMID: 27840244. 2. Wang S, Tsui ST, Liu C, Song Y, Liu D. EGFR C797S mutation mediates resistance to third-generation inhibitors in T790M-positive non-small cell lung cancer. J Hematol Oncol. 2016 Jul 22;9(1):59. doi: 10.1186/s13045-016-0290-1. PMID: 27448564; PMCID: PMC4957905.
In vivo protocol: 1. Wang S, Song Y, Liu D. EAI045: The fourth-generation EGFR inhibitor overcoming T790M and C797S resistance. Cancer Lett. 2017 Jan 28;385:51-54. doi: 10.1016/j.canlet.2016.11.008. Epub 2016 Nov 10. PMID: 27840244. 2. Jia Y, Yun CH, Park E, Ercan D, Manuia M, Juarez J, Xu C, Rhee K, Chen T, Zhang H, Palakurthi S, Jang J, Lelais G, DiDonato M, Bursulaya B, Michellys PY, Epple R, Marsilje TH, McNeill M, Lu W, Harris J, Bender S, Wong KK, Jänne PA, Eck MJ. Overcoming EGFR(T790M) and EGFR(C797S) resistance with mutant-selective allosteric inhibitors. Nature. 2016 Jun 2;534(7605):129-32. doi: 10.1038/nature17960. Epub 2016 May 25. PMID: 27251290; PMCID: PMC4929832.

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1: Wang S, Tsui ST, Liu C, Song Y, Liu D. EGFR C797S mutation mediates resistance
to third-generation inhibitors in T790M-positive non-small cell lung cancer. J
Hematol Oncol. 2016 Jul 22;9(1):59. doi: 10.1186/s13045-016-0290-1. Review.
PubMed PMID: 27448564; PubMed Central PMCID: PMC4957905.


2: Jia Y, Yun CH, Park E, Ercan D, Manuia M, Juarez J, Xu C, Rhee K, Chen T,
Zhang H, Palakurthi S, Jang J, Lelais G, DiDonato M, Bursulaya B, Michellys PY,
Epple R, Marsilje TH, McNeill M, Lu W, Harris J, Bender S, Wong KK, Jänne PA, Eck
MJ. Overcoming EGFR(T790M) and EGFR(C797S) resistance with mutant-selective
allosteric inhibitors. Nature. 2016 May 25;534(7605):129-32. doi:
10.1038/nature17960. PubMed PMID: 27251290; PubMed Central PMCID: PMC4929832.