A3001-5mg | PCI-32765 (Ibrutinib) [936563-96-1] Clinisciences

Background

PCI-32765, also named as Ibrutinib, is a Bruton tyrosine kinase inhibitor which is used to study the biological effects of Bruton tyrosine kinase inhibition on mature B-cell function and the progression of B cell-associated diseases in vivo. The Bruton tyrosine kinase is specifically necessary for BCR signaling as demonstrated by human and mouse mutations that disrupt Bruton tyrosine kinase function and prevent B-cell maturation at steps which need a functional BCR pathway. PCI-32765 also inhibited autoantibody production. Occupancy of the Bruton tyrosine kinase active site by PCI-32765 was monitored in vitro and in vivo using a fluorescent affinity probe for Bruton tyrosine kinase.

Reference

Lee A. Honigberga, Ashley M. Smitha, Mint Sirisawada, Erik Vernera, David Lourya, Betty Changa, Shyr Lib, Zhengying Panb,d, Douglas H. Thamme, Richard A. Millera, and Joseph J. Buggya. The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy. PNAS. 2010; 107(29): 13075 – 80.

Product Citation

1. Suyog Pol, Ravendra Dhanraj, et al. "Protective Effect of Bruton Tyrosine Kinase Inhibitor in Murine Model of Chronic Demyelination." Research Square September 27th, 2022.
2. Madison Barbara Allerton Hagger. "The Synergy of Adenosine and Ibrutinib on Platelet Aggregation in Chronic Lymphocytic Leukemia." Murdoch University 2021.
3. Alhakeem SS, McKenna MK, et al. "Chronic Lymphocytic Leukemia-Derived IL-10 Suppresses Antitumor Immunity." J Immunol. 2018 Jun 15;200(12):4180-4189. PMID: 29712773
4. Schroeder JT, Bieneman AP. "Activation of Human Basophils by A549 Lung Epithelial Cells Reveals a Novel IgE-Dependent Response Independent of Allergen." J Immunol. 2017 Aug 1;199(3):855-865. PMID: 28652400
5. Kosowicz JG, Lee J, et al. "Drug modulators of B cell signaling pathways and Epstein-Barr virus lytic activation." J Virol. 2017 May 31. pii: JVI.00747-17. PMID: 28566383
6. Lee DD, Muskaj I, et al. "Platelet proteins cause basophil histamine release through an immunoglobulin-dependent mechanism." Transfusion. 2017 May 4. PMID: 28470742

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Chemical Properties

Physical Appearance	A solid
Storage	Desiccate at -20°C
M.Wt	440.5
Cas No.	936563-96-1
Formula	C₂₅H₂₄N₆O₂
Synonyms	PCI-32765,Ibrutinib,CRA-032765
Solubility	≥22.02 mg/mL in DMSO; insoluble in H2O; ≥10.4 mg/mL in EtOH with ultrasonic
Chemical Name	2-[(2R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide
SDF	Download SDF
Canonical SMILES	C=CC(=O)N1CCCC(C1)N2C3=C(C(=N2)C4=CC=C(C=C4)OC5=CC=CC=C5)C(=NC=N3)N
Shipping Condition	Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice.
General tips	We do not recommend long-term storage for the solution, please use it up soon.

Protocol

Cell experiment:
Cell lines	CLL cell lines
Preparation method	The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months.
Reaction Conditions	24 h,48 h and 72 h; 1 μM.
Applications	Anti-IgM–supported CLL cell viability was reduced in the presence of PCI-32765 from 69% to 33% at 24 hours, and to 31% and 29% after 48 and 72 hours, respectively. Anti-IgM stimulation induced an average 27%±12% increase in viability after 24 hours compared with unstimulated controls. Preincubation with 1 μM PCI-32765 before anti-IgM stimulation significantly reduced CLL cell viability to 98%±8% of unstimulated controls. Survival signals from NLCs were also effectively inhibited by PCI-32765.
Animal experiment:
Animal models	CB17 SCID mice and Eμ-TCL1 transgenic (Tg) mice on a C3H/BL6 background
Dosage form	Suboptimal (2.5 mg/kg/d); optimal (25 mg/kg/d)
Applications	In the adoptive transfer TCL1 mouse model, animals treated PCI-32765 at 2 weeks post cell transfer with the suboptimal (2.5 mg/kg/d) and optimal (25 mg/kg/d) doses exhibited a transient lymphocytosis at day 4, with an average of 7- and 10-fold increases in circulating TCL1 leukemia cells, respectively.
Other notes	Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
References: [1] Ponader S, Chen S S, Buggy J J, et al. The Bruton tyrosine kinase inhibitor PCI-32765 thwarts chronic lymphocytic leukemia cell survival and tissue homing in vitro and in vivo[J]. Blood, 2012, 119(5): 1182-1189.

Biological Activity

Description	Ibrutinib is a potent and highly selective inhibitor of Btk with IC50 of 0.5 nM, modestly potent to Bmx, CSK, FGR, BRK, HCK, less potent to EGFR, Yes, ErbB2, JAK3, etc.
Targets	Btk
IC50	0.5 nM