NT113 is a novel and potent pan-ERBB inhibitor with anticancet/anti-glioma activities. Exhibiting IC50s of 0.4, 4.35, 4.18 and 2.08 nM for EGFR, EGFRT790M, ERBB2/HER2 and ERBB4/HER4, respectively.

Physicochemical Properties

Molecular Formula	C21H21CLFN5O
Molecular Weight	413.875746488571
Exact Mass	505.168
CAS #	1398833-56-1
PubChem CID	60172363
Appearance	Typically exists as solid at room temperature
LogP	4
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	7
Heavy Atom Count	36
Complexity	880
Defined Atom Stereocenter Count	2
SMILES	CN(C)C/C=C/C(=O)NC1=CC2=C(C=C1C#CC3[C@H]4[C@@H]3COC4)N=CN=C2NC5=CC(=C(C=C5)F)Cl
InChi Key	NQSNDWQDQPMUOC-DWJJLMPSSA-N
InChi Code	InChI=1S/C27H25ClFN5O2/c1-34(2)9-3-4-26(35)33-24-12-19-25(10-16(24)5-7-18-20-13-36-14-21(18)20)30-15-31-27(19)32-17-6-8-23(29)22(28)11-17/h3-4,6,8,10-12,15,18,20-21H,9,13-14H2,1-2H3,(H,33,35)(H,30,31,32)/b4-3+/t18?,20-,21+
Chemical Name	(E)-N-[4-(3-chloro-4-fluoroanilino)-7-[2-[(1R,5S)-3-oxabicyclo[3.1.0]hexan-6-yl]ethynyl]quinazolin-6-yl]-4-(dimethylamino)but-2-enamide
Synonyms	NT 113 NT-113 NT113
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	IC50: EGFR:0.4 nM; ErbB2:4.18 nM; ErbB4:2.08 nM; EGFRT790M:4.35 nM
ln Vitro	NT113 shows inhibitory activity against U87vIII cells, with IC50 of 0.19 μM[1].
ln Vivo	NT113 (20 mg/kg/day) shows inhibitory activity against intracranial EGFRvIII-amplified GBM39 xenograft tumors. NT113 (10 mg/kg/day) causes growth delay in the U87vIII intracranial xenografts. Mice receiving NT113 treatment survive significantly longer than mice receiving lapatinib[1].
Cell Assay	Cells are seeded in 96 well plates: 2000 cells/well in 200 μL, in hextuplicate. One day after seeding, 1 μL of DMSO, with or without NT113, is added to cells to achieve NT113 concentrations between 0.01 and 20.0 μM. Seventy-two hours later, WST-1 reagent is added, and sample 450 nm absorbance determined using a microplate reader, with background reading at 800 nm subtracted.
References	:NT113, a pan-ERBB inhibitor with high brain penetrance, inhibits the growth of glioblastoma xenografts with EGFR amplification. Mol Cancer Ther. 2014 Dec;13(12):2919-29.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.4162 mL	12.0808 mL	24.1616 mL
	5 mM	0.4832 mL	2.4162 mL	4.8323 mL
	10 mM	0.2416 mL	1.2081 mL	2.4162 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.