PF-06465469 (PF06465469) is a novel, potent and covalent inhibitor of ITK (IL-2 inducible T-cell kinase, a nonreceptor tyrosine kinase) with an IC50 of 2 nM. ITK is predominantly expressed in immune cells and experiences a significant upregulation after T-cell activation.

Physicochemical Properties

Molecular Formula	C30H33N7O2
Molecular Weight	523.62872
Exact Mass	523.27
Elemental Analysis	C, 68.81; H, 6.35; N, 18.72; O, 6.11
CAS #	1407966-77-1
Related CAS #	1407966-77-1
PubChem CID	71450146
Appearance	White to off-white solid powder
LogP	5.701
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	6
Heavy Atom Count	39
Complexity	883
Defined Atom Stereocenter Count	1
SMILES	C(N1CCCC(N2C3=NC=NC(N)=C3C(C3=CC=CC(C(NC4C=C(C)C(C(C)C)=CC=4)=O)=C3)=N2)C1)(=O)C=C
InChi Key	CGJVMKJGKFEHTL-HSZRJFAPSA-N
InChi Code	InChI=1S/C30H33N7O2/c1-5-25(38)36-13-7-10-23(16-36)37-29-26(28(31)32-17-33-29)27(35-37)20-8-6-9-21(15-20)30(39)34-22-11-12-24(18(2)3)19(4)14-22/h5-6,8-9,11-12,14-15,17-18,23H,1,7,10,13,16H2,2-4H3,(H,34,39)(H2,31,32,33)/t23-/m1/s1
Chemical Name	3-[4-amino-1-[(3R)-1-prop-2-enoylpiperidin-3-yl]pyrazolo[3,4-d]pyrimidin-3-yl]-N-(3-methyl-4-propan-2-ylphenyl)benzamide
Synonyms	PF-6465469; PF-06465469; PF 6465469; PF 06465469; PF6465469; PF06465469
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	ITK (IC50 = 2 nM)
References	[1]. Comparison of interleukin-2-inducible kinase (ITK) inhibitors and potential for combination therapies for T-cell lymphoma. Sci Rep. 2018 Sep 21;8(1):14216.

Solubility Data

Solubility (In Vitro)

DMSO: ~11 mg/mL (~21.0 mM)

Solubility (In Vivo)

Solubility in Formulation 1: 1.1 mg/mL (2.10 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 11.0 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: ≥ 1.1 mg/mL (2.10 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 11.0 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. Solubility in Formulation 3: ≥ 1.1 mg/mL (2.10 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 11.0 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	1.9097 mL	9.5487 mL	19.0975 mL
	5 mM	0.3819 mL	1.9097 mL	3.8195 mL
	10 mM	0.1910 mL	0.9549 mL	1.9097 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.