UNC-CA359 is a potent epidermal growth factor receptor (EGFR) inhibitor (antagonist) with IC50 of 18 nM. UNC-CA359 has anti-tumor activity and may be utilized in chordoma research. UNC-CA359 is a reagent for click chemistry. It has Alkyne groups and could undergo CuAAc (copper-catalyzed azide-alkyne cycloaddition reaction) with compounds bearing Azide groups.

Physicochemical Properties

Molecular Formula	C18H14CLN3O2
Molecular Weight	339.775662899017
Exact Mass	339.077
CAS #	2676156-05-9
PubChem CID	164886643
Appearance	Typically exists as solid at room temperature
LogP	4.2
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	5
Heavy Atom Count	24
Complexity	468
Defined Atom Stereocenter Count	0
InChi Key	KQFANGBOVPXOEP-UHFFFAOYSA-N
InChi Code	InChI=1S/C18H14ClN3O2/c1-4-11-7-12(5-6-14(11)19)22-18-13-8-16(23-2)17(24-3)9-15(13)20-10-21-18/h1,5-10H,2-3H3,(H,20,21,22)
Chemical Name	N-(4-chloro-3-ethynylphenyl)-6,7-dimethoxyquinazolin-4-amine
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

ln Vitro	UNC-CA359 (compound 45) exhibits decreased activity on U-CH1, some activity on U-CH2, and continues to inhibit EGFR; its IC50 values are >100 μM, 35 μM, and 18 nM, respectively [1]. The anti-chordoma activity of UNC-CA359 (1 nM-0.1 mM; 72 h) is 1.2 μM (CH22) and 3.0 μM (U-CH12) [1]. Compound 102, UNC-CA359, exhibits three primary incidental kinase targets and a high level of potency against SLK/STK10, with a selectivity ratio of 22 (NAK vs SLK/STK10) and binding constant Ki values of 3.4 nM (GAK), 0.33 μM (SLK), and 0.075 μM (STK10), in that order [2]. Serine/threonine protein kinase 10 is known as STK10; cyclin G-related kinase (GAK) is known as SLK (STE20-like serine/threonine protein kinase).
Cell Assay	Cytotoxicity assay [1] Cell Types: Chordoma Cell Types: CH22, UM- Chor1, U-CH12 and U-CH7; WS1 Tested Concentrations: 1 nM-100 μM Incubation Duration: 72 hrs (hours) Experimental Results: Shows good potential against chordoma cells with IC50 of 1.2 μM (CH22), 3.0 μM (U-CH12) , 60 μM (UM-Chor1), 74 μM (U-CH7), respectively. No toxicity to WS1 cells (IC50 >100 μM).
References	[1]. Bieberich AA, et al. Optimization of the 4-anilinoquin(az)oline scaffold as epidermal growth factor receptor (EGFR) inhibitors for chordoma utilizing a toxicology profiling assay platform. Sci Rep. 2022 Jul 27. 12(1):12820. [2]. Asquith CRM, et al. Design and Analysis of the 4-Anilinoquin(az)oline Kinase Inhibition Profiles of GAK/SLK/STK10 Using Quantitative Structure-Activity Relationships. ChemMedChem. 2020 Jan 7. 15(1):26-49.

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	2.9431 mL	14.7154 mL	29.4308 mL
	5 mM	0.5886 mL	2.9431 mL	5.8862 mL
	10 mM	0.2943 mL	1.4715 mL	2.9431 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.