EAI045|cas 1942114-09-1|DC Chemicals

Cas No.:	1942114-09-1
Chemical Name:	2-(5-Fluoro-2-hydroxyphenyl)-2-(3-oxo-1H-isoindol-2-yl)-N-(1,3-thiazol-2-yl)acetamide
Synonyms:	EAI045;EAI-045;2-(5-fluoro-2-hydroxyphenyl)-2-(3-oxo-1H-isoindol-2-yl)-N-(1,3-thiazol-2-yl)acetamide;2-(5-fluoro-2-hydroxyphenyl)-2-(1-oxo-2,3-dihydro-1H-isoindol-2-yl)-N-(1,3-thiazol-2-yl)acetamide;GTPL9222;BCP17698;s8242;EA1045;AK607730;2-(5-Fluoro-2-hydroxyphenyl)-2-(1-oxoisoindolin-2-yl)-N-(thiazol-2-yl)acetamide
SMILES:	S1C([H])=C([H])N=C1N([H])C(C([H])(C1C([H])=C(C([H])=C([H])C=1O[H])F)N1C(C2=C([H])C([H])=C([H])C([H])=C2C1([H])[H])=O)=O
Formula:	C₁₉H₁₄FN₃O₃S
M.Wt:	383.3962
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	EAI045 is an allosteric 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 Vivo:	In a genetically engineered mouse model of L858R/T790Mmutant-driven lung cancer , remarkable tumor regression is observed in L858R/T790M-mutant mice treated with the combination of EAI045 and cetuximab. No response is seen in those mice treated with EAI045 alone. The same effect is seen in both L858R/T790M/C797S- engineered Ba/F3 cells and in mice carrying the L858R/T790M/C797S tumor xenografts. These assays clearly show that EAI045 can overcome resistance from acquired T790M and C797S mutations[2].
In Vitro:	EAI045 potently inhibits EGFR Y1173 phosphorylation in H1975 cells (EC50=2 nM), but not in HaCaT cells. EAI045 is an inhibitor of the L858R/T790M mutant with 1000-fold selectivity versus wild type EGFR at 1 mM ATP. Profiling of EAI045 against a panel of 250 protein kinases reveals exquisite selectivity; no other kinases are inhibited by more than 20% at 1 μM EAI045[1]. EAI045 has high potency and selectivity for L858R/T790M mutation. In L858R/T790M-mutant NSCLC cell line H1975 cells, EAI045 decreases but does not completely abolish the EGFR autophosphorylation. In stably transfected NIH-3T3 cells harboring the L858R/T790M EGFR mutant, EAI045 shows the same activity. In L858R-mutant H3255 cells, EAI045 exhibits moderate activity. In the HaCaT cells, a keratinocyte cell line with wild-type EGFR, EAI045 does not show any activity of inhibiting EGFR phosphorylation. It confirms the selectivity of EAI045 for mutant EGFR[2].

Cat. No.	Product name	Field of application
DC70520	JBJ-09-063	JBJ-09-063 is a potent, mutant-selective allosteric EGFR inhibitor against EGFR L858R, T790M and C797S mutations, with IC50 of <0.1 nM for recombinant EGFR L858R/T790M kinase domain.
DC40932	JCN037	JCN037 (JGK037) is non-covalent and BBB-penetrant EGFR tyrosine kinase inhibitor, with IC50 values of 2.49 nM, 3.95 nM, 4.48 nM for EGFR, p-wtEGFR and pEGFRvⅢ, respectively.
DC7622	BIBX1382	BIBX 1382 is a potent, selective inhibitor of EGFR tyrosine kinase (IC50 = 3 nM); displays > 1000-fold lower potency against ErbB2 (IC50 = 3.4 μM) and a range of other related tyrosine kinases (IC50 > 10 μM).
DC12161	TAS6417	TAS6417 is an EGFR inhibitor and an efficacious drug candidate for patients with NSCLC, with IC50 values ranging from 1.1-8.0 nM.
DC10764	Theliatinib (HMPL-309)	Theliatinib (HMPL-309) is a novel small molecule, EGFR tyrosine kinase inhibitor with potential antineoplastic and anti-angiogenesis activities.
DC5090	WZ4002	WZ4002 is a novel, mutant-selective EGFR inhibitor for EGFR(L858R)/(T790M) with IC50 of 2 nM/8 nM; does not inhibit ERBB2 phosphorylation (T798I).
DC9775	WZ3146	WZ3146 is a mutant-selective irreversible inhibitor of EGFR(L858R) and EGFR(E746_A750) with IC50 of 2 nM and 2 nM; does not inhibit ERBB2 phosphorylation (T798I).
DC10519	SU 5214	SU 5214 is a modulator of tyrosine kinase signal transduction.
DC7078	AZD-8931(Sapitinib)	Sapitinib(AZD8931) is a reversible, ATP competitive inhibitor of EGFR, ErbB2 and ErbB3 with IC50 of 4 nM, 3 nM and 4 nM respectively.
DC10479	RX518(CK-101:EGFR-IN-3)	RX518(CK-101) is an orally available third-generation and selective inhibitor of certain epidermal growth factor receptor (EGFR) activating mutations.