ITK inhibitor

Potent ITK inhibitor CAS# 439574-61-5

ITK inhibitor

Catalog No. BCC1662----Order now to get a substantial discount!

Product Name & Size Price Stock
ITK inhibitor: 5mg $242 In Stock
ITK inhibitor: 10mg Please Inquire In Stock
ITK inhibitor: 20mg Please Inquire Please Inquire
ITK inhibitor: 50mg Please Inquire Please Inquire
ITK inhibitor: 100mg Please Inquire Please Inquire
ITK inhibitor: 200mg Please Inquire Please Inquire
ITK inhibitor: 500mg Please Inquire Please Inquire
ITK inhibitor: 1000mg Please Inquire Please Inquire
Related Products
  • BMS-509744

    Catalog No.:BCC1424
    CAS No.:439575-02-7

Quality Control of ITK inhibitor

Number of papers citing our products

Chemical structure

ITK inhibitor

3D structure

Chemical Properties of ITK inhibitor

Cas No. 439574-61-5 SDF Download SDF
PubChem ID 20635522 Appearance Powder
Formula C31H39N5O4S2 M.Wt 609.82
Type of Compound N/A Storage Desiccate at -20°C
Solubility Soluble in DMSO
Chemical Name N-[5-[5-(4-acetylpiperazine-1-carbonyl)-4-methoxy-2-methylphenyl]sulfanyl-1,3-thiazol-2-yl]-4-[(3-methylbutan-2-ylamino)methyl]benzamide
SMILES CC1=C(C=C(C(=C1)OC)C(=O)N2CCN(CC2)C(=O)C)SC3=CN=C(S3)NC(=O)C4=CC=C(C=C4)CNC(C)C(C)C
Standard InChIKey RRHONYZEMUNMJX-UHFFFAOYSA-N
Standard InChI InChI=1S/C31H39N5O4S2/c1-19(2)21(4)32-17-23-7-9-24(10-8-23)29(38)34-31-33-18-28(42-31)41-27-16-25(26(40-6)15-20(27)3)30(39)36-13-11-35(12-14-36)22(5)37/h7-10,15-16,18-19,21,32H,11-14,17H2,1-6H3,(H,33,34,38)
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months.
Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it.
About Packaging 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial.
2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial.
3. Try to avoid loss or contamination during the experiment.
Shipping Condition Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request.

Biological Activity of ITK inhibitor

DescriptionITK inhibitor is a potent inhibitor of ITK.
TargetsITK    

ITK inhibitor Dilution Calculator

Concentration (start)
x
Volume (start)
=
Concentration (final)
x
Volume (final)
 
 
 
C1
V1
C2
V2

calculate

ITK inhibitor Molarity Calculator

Mass
=
Concentration
x
Volume
x
MW*
 
 
 
g/mol

calculate

Preparing Stock Solutions of ITK inhibitor

1 mg 5 mg 10 mg 20 mg 25 mg
1 mM 1.6398 mL 8.1991 mL 16.3983 mL 32.7966 mL 40.9957 mL
5 mM 0.328 mL 1.6398 mL 3.2797 mL 6.5593 mL 8.1991 mL
10 mM 0.164 mL 0.8199 mL 1.6398 mL 3.2797 mL 4.0996 mL
50 mM 0.0328 mL 0.164 mL 0.328 mL 0.6559 mL 0.8199 mL
100 mM 0.0164 mL 0.082 mL 0.164 mL 0.328 mL 0.41 mL
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations.

Organizitions Citing Our Products recently

 
 
 

Calcutta University

University of Minnesota

University of Maryland School of Medicine

University of Illinois at Chicago

The Ohio State University

University of Zurich

Harvard University

Colorado State University

Auburn University

Yale University

Worcester Polytechnic Institute

Washington State University

Stanford University

University of Leipzig

Universidade da Beira Interior

The Institute of Cancer Research

Heidelberg University

University of Amsterdam

University of Auckland
TsingHua University
TsingHua University
The University of Michigan
The University of Michigan
Miami University
Miami University
DRURY University
DRURY University
Jilin University
Jilin University
Fudan University
Fudan University
Wuhan University
Wuhan University
Sun Yat-sen University
Sun Yat-sen University
Universite de Paris
Universite de Paris
Deemed University
Deemed University
Auckland University
Auckland University
The University of Tokyo
The University of Tokyo
Korea University
Korea University

Background on ITK inhibitor

Interleukin-2-inducible T cell kinase (ITK) is a non-receptor tyrosine kinase expressed in T cells, NKT cells and mast cells which plays a crucial role in regulating the T cell receptor (TCR), CD28, CD2, chemokine receptor CXCR4, and FcepsilonR-mediated signaling pathways. ITK inhibitors can be used for the treatment of inflammation and immune-mediated disorders. ITK inhibitor (N-[5-[[3-[(4-Acetylpiperazin-1-yl)carbonyl]-4-methyl-6-methoxy-phenyl]thio]thiazol-2-yl]-4-(N-1,2-dimethylpropylaminomethyl)benzamide) is the analogue of BMS-509744, which can potently and selectively inhibit Itk kinase activity.

In vitro: BMS-509744 could reduce TCR-induced functions including PLCγ1 tyrosine phosphorylation, calcium mobilization, IL-2 secretion, and T-cell proliferation in vitro in both human and mouse cells [1].

In vivo: BMS-509744 suppressed the production of IL-2 induced by anti-TCR antibody administered to mice. BMS-509744 also significantly diminishes lung inflammation in a mouse model of ovalbumin-induced allergy/asthma [1].

Clinical trial: Up to now, both BMS-509744 and ITK inhibitor is still in the preclinical development stage.

Reference:
[1] Lin TA, McIntyre KW, Das J, Liu C, O'Day KD, Penhallow B, Hung CY, Whitney GS, Shuster DJ, Yang X, Townsend R, Postelnek J, Spergel SH, Lin J, Moquin RV, Furch JA, Kamath AV, Zhang H, Marathe PH, Perez-Villar JJ, Doweyko A, Killar L, Dodd JH, Barrish JC, Wityak J, Kanner SB.  Selective Itk inhibitors block T-cell activation and murine lung inflammation. Biochemistry. 2004 Aug 31;43(34):11056-62.

Featured Products
New Products
 

References on ITK inhibitor

Ibrutinib is an irreversible molecular inhibitor of ITK driving a Th1-selective pressure in T lymphocytes.[Pubmed:23886836]

Blood. 2013 Oct 10;122(15):2539-49.

Given its critical role in T-cell signaling, interleukin-2-inducible kinase (ITK) is an appealing therapeutic target that can contribute to the pathogenesis of certain infectious, autoimmune, and neoplastic diseases. Ablation of ITK subverts Th2 immunity, thereby potentiating Th1-based immune responses. While small-molecule ITK inhibitors have been identified, none have demonstrated clinical utility. Ibrutinib is a confirmed irreversible inhibitor of Bruton tyrosine kinase (BTK) with outstanding clinical activity and tolerability in B-cell malignancies. Significant homology between BTK and ITK alongside in silico docking studies support ibrutinib as an immunomodulatory inhibitor of both ITK and BTK. Our comprehensive molecular and phenotypic analysis confirms ITK as an irreversible T-cell target of ibrutinib. Using ibrutinib clinical trial samples along with well-characterized neoplastic (chronic lymphocytic leukemia), parasitic infection (Leishmania major), and infectious disease (Listeria monocytogenes) models, we establish ibrutinib as a clinically relevant and physiologically potent ITK inhibitor with broad therapeutic utility. This trial was registered at www.clinicaltrials.gov as #NCT01105247 and #NCT01217749.

A Small Molecule Inhibitor of ITK and RLK Impairs Th1 Differentiation and Prevents Colitis Disease Progression.[Pubmed:26466958]

J Immunol. 2015 Nov 15;195(10):4822-31.

In T cells, the Tec kinases IL-2-inducible T cell kinase (ITK) and resting lymphocyte kinase (RLK) are activated by TCR stimulation and are required for optimal downstream signaling. Studies of CD4(+) T cells from Itk(-/-) and Itk(-/-)Rlk(-/-) mice have indicated differential roles of ITK and RLK in Th1, Th2, and Th17 differentiation and cytokine production. However, these findings are confounded by the complex T cell developmental defects in these mice. In this study, we examine the consequences of ITK and RLK inhibition using a highly selective and potent small molecule covalent inhibitor PRN694. In vitro Th polarization experiments indicate that PRN694 is a potent inhibitor of Th1 and Th17 differentiation and cytokine production. Using a T cell adoptive transfer model of colitis, we find that in vivo administration of PRN694 markedly reduces disease progression, T cell infiltration into the intestinal lamina propria, and IFN-gamma production by colitogenic CD4(+) T cells. Consistent with these findings, Th1 and Th17 cells differentiated in the presence of PRN694 show reduced P-selectin binding and impaired migration to CXCL11 and CCL20, respectively. Taken together, these data indicate that ITK plus RLK inhibition may have therapeutic potential in Th1-mediated inflammatory diseases.

Targeting interleukin-2-inducible T-cell kinase (ITK) and resting lymphocyte kinase (RLK) using a novel covalent inhibitor PRN694.[Pubmed:25593320]

J Biol Chem. 2015 Mar 6;290(10):5960-78.

Interleukin-2-inducible T-cell kinase (ITK) and resting lymphocyte kinase (RLK or TXK) are essential mediators of intracellular signaling in both normal and neoplastic T-cells and natural killer (NK) cells. Thus, ITK and RLK inhibitors have therapeutic potential in a number of human autoimmune, inflammatory, and malignant diseases. Here we describe a novel ITK/RLK inhibitor, PRN694, which covalently binds to cysteine residues 442 of ITK and 350 of RLK and blocks kinase activity. Molecular modeling was utilized to design molecules that interact with cysteine while binding to the ATP binding site in the kinase domain. PRN694 exhibits extended target residence time on ITK and RLK and is highly selective for a subset of the TEC kinase family. In vitro cellular assays confirm that PRN694 prevents T-cell receptor- and Fc receptor-induced cellular and molecular activation, inhibits T-cell receptor-induced T-cell proliferation, and blocks proinflammatory cytokine release as well as activation of Th17 cells. Ex vivo assays demonstrate inhibitory activity against T-cell prolymphocytic leukemia cells, and in vivo assays demonstrate durable pharmacodynamic effects on ITK, which reduces an oxazolone-induced delayed type hypersensitivity reaction. These data indicate that PRN694 is a highly selective and potent covalent inhibitor of ITK and RLK, and its extended target residence time enables durable attenuation of effector cells in vitro and in vivo. The results from this study highlight potential applications of this dual inhibitor for the treatment of T-cell- or NK cell-mediated inflammatory, autoimmune, and malignant diseases.

Therapeutic antitumor immunity by checkpoint blockade is enhanced by ibrutinib, an inhibitor of both BTK and ITK.[Pubmed:25730880]

Proc Natl Acad Sci U S A. 2015 Mar 3;112(9):E966-72.

Monoclonal antibodies can block cellular interactions that negatively regulate T-cell immune responses, such as CD80/CTLA-4 and PD-1/PD1-L, amplifying preexisting immunity and thereby evoking antitumor immune responses. Ibrutinib, an approved therapy for B-cell malignancies, is a covalent inhibitor of BTK, a member of the B-cell receptor (BCR) signaling pathway, which is critical to the survival of malignant B cells. Interestingly this drug also inhibits ITK, an essential enzyme in Th2 T cells and by doing so it can shift the balance between Th1 and Th2 T cells and potentially enhance antitumor immune responses. Here we report that the combination of anti-PD-L1 antibody and ibrutinib suppresses tumor growth in mouse models of lymphoma that are intrinsically insensitive to ibrutinib. The combined effect of these two agents was also documented for models of solid tumors, such as triple negative breast cancer and colon cancer. The enhanced therapeutic activity of PD-L1 blockade by ibrutinib was accompanied by enhanced antitumor T-cell immune responses. These preclinical results suggest that the combination of PD1/PD1-L blockade and ibrutinib should be tested in the clinic for the therapy not only of lymphoma but also in other hematologic malignancies and solid tumors that do not even express BTK.

Description

ITK inhibitor is a potent ITK inhibitor.

Keywords:

ITK inhibitor,439574-61-5,Natural Products,ITK, buy ITK inhibitor , ITK inhibitor supplier , purchase ITK inhibitor , ITK inhibitor cost , ITK inhibitor manufacturer , order ITK inhibitor , high purity ITK inhibitor

Online Inquiry for:

      Fill out the information below

      • Size:Qty: - +

      * Required Fields

                                      Result: