Vepafestinib (TAS0953/HM06; compound 6) is an inhibitor (blocker/antagonist) of RET (information from patent WO2019039439). Vepafestinib is a click chemical agent. It contains Alkyne groups and could undergo CuAAc (copper-catalyzed azide-alkyne cycloaddition reaction) with compounds bearing an Azide group.

Physicochemical Properties

Molecular Formula	C26H30N6O3
Molecular Weight	474.5548
Exact Mass	474.237
CAS #	2129515-96-2
PubChem CID	134164132
Appearance	Light yellow to yellow solid powder
LogP	1.3
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	7
Heavy Atom Count	35
Complexity	808
Defined Atom Stereocenter Count	0
SMILES	O=C(C1C2=C(N([H])[H])N=C([H])N=C2N(C=1C#CC([H])([H])N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H])C1(C([H])([H])[H])C([H])([H])C1([H])[H])N([H])C1C([H])=C([H])C(C([H])([H])OC([H])([H])[H])=C([H])C=1[H]
InChi Key	SFXVRNLGOSAWIV-UHFFFAOYSA-N
InChi Code	InChI=1S/C26H30N6O3/c1-26(9-10-26)32-20(4-3-11-31-12-14-35-15-13-31)21(22-23(27)28-17-29-24(22)32)25(33)30-19-7-5-18(6-8-19)16-34-2/h5-8,17H,9-16H2,1-2H3,(H,30,33)(H2,27,28,29)
Chemical Name	4-amino-N-[4-(methoxymethyl)phenyl]-7-(1-methylcyclopropyl)-6-(3-morpholin-4-ylprop-1-ynyl)pyrrolo[2,3-d]pyrimidine-5-carboxamide
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

References

[1]. FUSION PROTEIN OF DCTN1 PROTEIN WITH RET PROTEIN. WO2019039439.

Additional Infomation

Vepafestinib is an orally bioavailable selective inhibitor of wild-type, fusion products and mutated forms of the proto-oncogene receptor tyrosine kinase rearranged during transfection (RET), with potential antineoplastic activity. Upon oral administration, vepafestinib selectively binds to and inhibits the activity of RET. This results in an inhibition of cell growth of tumors cells that exhibit increased RET activity. RET overexpression, activating mutations, and fusions result in the upregulation and/or overactivation of RET tyrosine kinase activity in various cancer cell types; dysregulation of RET activity plays a key role in the development and progression of these cancers.

Solubility Data

Solubility (In Vitro)

DMSO: 50 mg/mL (105.36 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 1 mg/mL (2.11 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 + to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.1073 mL	10.5363 mL	21.0726 mL
	5 mM	0.4215 mL	2.1073 mL	4.2145 mL
	10 mM	0.2107 mL	1.0536 mL	2.1073 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.