RET-IN-3 (compound 34) is a selective RETV804M kinase inhibitor (antagonist) with IC50 of 19 nM.

Physicochemical Properties

Molecular Formula	C18H21N5O2
Molecular Weight	339.391643285751
Exact Mass	339.169
CAS #	2414374-53-9
PubChem CID	146018674
Appearance	Off-white to light yellow solid powder
LogP	2.5
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	6
Heavy Atom Count	25
Complexity	438
Defined Atom Stereocenter Count	0
SMILES	O1COC2=CC=C(C=C12)C1C=NN2C=CC(=NC2=1)NCCCN(C)C
InChi Key	DQYRQFLRDJTHQM-UHFFFAOYSA-N
InChi Code	InChI=1S/C18H21N5O2/c1-22(2)8-3-7-19-17-6-9-23-18(21-17)14(11-20-23)13-4-5-15-16(10-13)25-12-24-15/h4-6,9-11H,3,7-8,12H2,1-2H3,(H,19,21)
Chemical Name	N-[3-(1,3-benzodioxol-5-yl)pyrazolo[1,5-a]pyrimidin-5-yl]-N',N'-dimethylpropane-1,3-diamine
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: 19 nM (RETV804M)[1].
ln Vitro	When RET-IN-3 is compared to wt-RET and KDR, it shows 16 and 410 fold selectivity, respectively[1].
References	[1]. Discovery and Optimization of wt-RET/KDR-Selective Inhibitors of RET V804M Kinase. ACS Med Chem Lett. 2020 Feb 28;11(4):497-505.

Solubility Data

Solubility (In Vitro)

DMSO: 100 mg/mL (294.65 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.37 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 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 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.37 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.9465 mL	14.7323 mL	29.4646 mL
	5 mM	0.5893 mL	2.9465 mL	5.8929 mL
	10 mM	0.2946 mL	1.4732 mL	2.9465 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.