Ibrutinib deacryloylpiperidine (IBT4A) is an impurity of Ibrutinib. Ibrutinib is an irreversible and selective Btk inhibitor (antagonist) with IC50 of 0.5 nM.

Physicochemical Properties

Molecular Formula	C17H13N5O
Molecular Weight	303.32
Exact Mass	303.112
Elemental Analysis	C, 68.17; H, 5.49; N, 19.08; O, 7.26
CAS #	330786-24-8
PubChem CID	22346757
Appearance	Off-white to gray solid powder
Density	1.4±0.1 g/cm3
Boiling Point	577.4±50.0 °C at 760 mmHg
Flash Point	303.0±30.1 °C
Vapour Pressure	0.0±1.6 mmHg at 25°C
Index of Refraction	1.734
LogP	3.01
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	3
Heavy Atom Count	23
Complexity	381
Defined Atom Stereocenter Count	0
InChi Key	YYVUOZULIDAKRN-UHFFFAOYSA-N
InChi Code	InChI=1S/C17H13N5O/c18-16-14-15(21-22-17(14)20-10-19-16)11-6-8-13(9-7-11)23-12-4-2-1-3-5-12/h1-10H,(H3,18,19,20,21,22)
Chemical Name	3-(4-phenoxyphenyl)-2H-pyrazolo[3,4-d]pyrimidin-4-amine
Synonyms	330786-24-8; 3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine; 4-Amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidine; Ibrutinib deacryloylpiperidine; Ibrutinib N-2; MFCD20270360; 3-(4-phenoxyphenyl)-2H-pyrazolo[3,4-d]pyrimidin-4-amine; 1H-Pyrazolo[3,4-d]pyrimidin-4-amine, 3-(4-phenoxyphenyl)-;
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 Note: This product requires protection from light (avoid light exposure) during transportation and storage.
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	BTK; impurity of Ibrutinib
References	[1]. A QUALITY BY DESIGN APPROACH FOR DEVELOPMENT OF SIMPLE AND ROBUST REVERSED PHASE STABILITY INDICATING HPLC METHOD FOR ESTIMATION OF IBRUTINIB AND ITS IMPURITIES. [2]. The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy. Proc Natl Acad Sci U S A. 2010 Jul 20;107(29):13075-80.
Additional Infomation	Activation of the B-cell antigen receptor (BCR) signaling pathway contributes to the initiation and maintenance of B-cell malignancies and autoimmune diseases. The Bruton tyrosine kinase (Btk) is specifically required for BCR signaling as demonstrated by human and mouse mutations that disrupt Btk function and prevent B-cell maturation at steps that require a functional BCR pathway. Herein we describe a selective and irreversible Btk inhibitor, PCI-32765, that is currently under clinical development in patients with B-cell non-Hodgkin lymphoma. We have used this inhibitor to investigate the biologic effects of Btk inhibition on mature B-cell function and the progression of B cell-associated diseases in vivo. PCI-32765 blocked BCR signaling in human peripheral B cells at concentrations that did not affect T cell receptor signaling. In mice with collagen-induced arthritis, orally administered PCI-32765 reduced the level of circulating autoantibodies and completely suppressed disease. PCI-32765 also inhibited autoantibody production and the development of kidney disease in the MRL-Fas(lpr) lupus model. Occupancy of the Btk active site by PCI-32765 was monitored in vitro and in vivo using a fluorescent affinity probe for Btk. Active site occupancy of Btk was tightly correlated with the blockade of BCR signaling and in vivo efficacy. Finally, PCI-32765 induced objective clinical responses in dogs with spontaneous B-cell non-Hodgkin lymphoma. These findings support Btk inhibition as a therapeutic approach for the treatment of human diseases associated with activation of the BCR pathway.[2]

Solubility Data

Solubility (In Vitro)

DMSO: 25 mg/mL (82.42 mM) H2O: < 0.1 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: 2.5 mg/mL (8.24 mM) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.2968 mL	16.4842 mL	32.9685 mL
	5 mM	0.6594 mL	3.2968 mL	6.5937 mL
	10 mM	0.3297 mL	1.6484 mL	3.2968 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.