Utatrectinib (AZD-7451) is a potent, selective and orally bioactive Trk inhibitor. Utatrectinib blocks TrkC activation and related tumorigenic behaviors.

Physicochemical Properties

Molecular Weight	382.394865274429
Exact Mass	382.166
CAS #	1079274-94-4
PubChem CID	25115967
Appearance	Typically exists as solid at room temperature
Density	1.5±0.1 g/cm3
Boiling Point	645.9±65.0 °C at 760 mmHg
Flash Point	344.4±34.3 °C
Vapour Pressure	0.0±1.9 mmHg at 25°C
Index of Refraction	1.712
LogP	1.04
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	6
Heavy Atom Count	28
Complexity	506
Defined Atom Stereocenter Count	1
SMILES	FC1C=NC([C@H](C)NC2=CC=C3C(=N2)N(C=N3)C2=CC(=NN2)OC(C)C)=NC=1
InChi Key	AYOOGWWGECJQPI-NSHDSACASA-N
InChi Code	InChI=1S/C18H19FN8O/c1-10(2)28-16-6-15(25-26-16)27-9-22-13-4-5-14(24-18(13)27)23-11(3)17-20-7-12(19)8-21-17/h4-11H,1-3H3,(H,23,24)(H,25,26)/t11-/m0/s1
Chemical Name	N-[(1S)-1-(5-fluoropyrimidin-2-yl)ethyl]-3-(3-propan-2-yloxy-1H-pyrazol-5-yl)imidazo[4,5-b]pyridin-5-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	Utatrectinib (100 nM, 22 hours) prevents U2SO cells that express TrkC from migrating [2]. KM12, H460, and H810 cell growth is inhibited by intratetrectinib (1–10 nM, 24 hours) [3]. In KM12 and H460 cells, utatrectinib (5 nM, 24 hours) suppresses TRKA/B phosphorylation and downstream signaling [3].
ln Vivo	In an ACCX6 xenograft nu/nu mice model, utetrectinib (50 mg/kg, oral, daily) suppresses the growth of adenoid cystic carcinoma (ACC) tumors [2].
Cell Assay	Cell migration assay [2] Cell Types: U2SO cells expressing TrkC Tested Concentrations: 100 nM Incubation Duration: 22 hrs (hours) Experimental Results: Cell migration was inhibited (approximately 2.3-fold, P<0.01). Western Blot Analysis [3] Cell Types: KM12, H460 Cell Tested Concentrations: 0, 1, 5 nM Incubation Duration: 24 hrs (hours) Experimental Results: pTRKA Tyr490 and pAk were inhibited in KM12 cells. Inhibition of pTRKB Tyr706/707 and pERK in H460 cells.
Animal Protocol	Animal/Disease Models: xenograft nu/nu mouse model of human ACC: ACCX6 and ACCX9[2] Doses: 50 mg/kg Route of Administration: Orally, daily. Experimental Results: Tumor Growth Inhibition (TGI): 64% (in ACCX6 model)
References	[1]. Combined use of Trk inhibitor containing heterocyclic urea derivative, and other kinase inhibitor for treating cancer. WO2019049891 A1. [2]. TrkC signaling is activated in adenoid cystic carcinoma and requires NT-3 to stimulate invasive behavior. Oncogene. 2013 Aug 8;32(32):3698-710. [3]. Investigation of neurotrophic tyrosine kinase receptor 1 fusions and neurotrophic tyrosine kinase receptor family expression in non-small-cell lung cancer and sensitivity to AZD7451 in vitro. Mol Clin Oncol. 2014 Sep;2(5):725-730.
Additional Infomation	Utatrectinib is a tropomyosin receptor kinase (TRK) inhibitor with potential antineoplastic activity. Upon administration, utatrectinib binds to TRK, thereby preventing the neurotrophin-TRK interaction and subsequent TRK activation. This may eventually result in an inhibition of tumor cell proliferation in TRK-expressing tumor cells. TRK, a receptor tyrosine kinase activated by neurotrophins, is mutated in a variety of cancer cell types and plays an important role in tumor cell growth, invasion and survival.

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	2.6151 mL	13.0757 mL	26.1513 mL
	5 mM	0.5230 mL	2.6151 mL	5.2303 mL
	10 mM	0.2615 mL	1.3076 mL	2.6151 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.