TAK-020 is a covalent/irreversible inhibitor of Btk and has become a clinical candidate active molecule.

Physicochemical Properties

Molecular Formula	C18H17N5O3
Molecular Weight	351.359283208847
Exact Mass	351.133
CAS #	1627603-21-7
PubChem CID	136286736
Appearance	White to off-white solid powder
LogP	2
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	4
Heavy Atom Count	26
Complexity	622
Defined Atom Stereocenter Count	1
SMILES	O(C1C2C=CC=CC=2C=C(C2=NNC(N2)=O)N=1)[C@@H]1CN(C(C=C)=O)CC1
InChi Key	HIMUHMBGRATXMK-LBPRGKRZSA-N
InChi Code	InChI=1S/C18H17N5O3/c1-2-15(24)23-8-7-12(10-23)26-17-13-6-4-3-5-11(13)9-14(19-17)16-20-18(25)22-21-16/h2-6,9,12H,1,7-8,10H2,(H2,20,21,22,25)/t12-/m0/s1
Chemical Name	3-[1-[(3S)-1-prop-2-enoylpyrrolidin-3-yl]oxyisoquinolin-3-yl]-1,4-dihydro-1,2,4-triazol-5-one
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]. Discovery of the Bruton's Tyrosine Kinase Inhibitor Clinical Candidate TAK-020 (S)-5-(1-((1-Acryloylpyrrolidin-3-yl)oxy)isoquinolin-3-yl)-2,4-dihydro-3H-1,2,4-triazol-3-one, by Fragment-Based Drug Design. J Med Chem. 2021 Sep 9;64(17):12893-12902.

Solubility Data

Solubility (In Vitro)

DMSO: 20.83 mg/mL (59.28 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 1.67 mg/mL (4.75 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 16.7 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: ≥ 1.67 mg/mL (4.75 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 16.7 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. Solubility in Formulation 3: ≥ 1.67 mg/mL (4.75 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 16.7 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.8461 mL	14.2304 mL	28.4608 mL
	5 mM	0.5692 mL	2.8461 mL	5.6922 mL
	10 mM	0.2846 mL	1.4230 mL	2.8461 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.