CNX-774

BTK inhibitor, orally active, irreversible and selective CAS# 1202759-32-7

CNX-774

Catalog No. BCC4394----Order now to get a substantial discount!

Product Name & Size Price Stock
CNX-774: 5mg $115 In Stock
CNX-774: 10mg Please Inquire In Stock
CNX-774: 20mg Please Inquire Please Inquire
CNX-774: 50mg Please Inquire Please Inquire
CNX-774: 100mg Please Inquire Please Inquire
CNX-774: 200mg Please Inquire Please Inquire
CNX-774: 500mg Please Inquire Please Inquire
CNX-774: 1000mg Please Inquire Please Inquire
Related Products
  • PF-4708671

    Catalog No.:BCC5031
    CAS No.:1255517-76-0
  • BIX 02565

    Catalog No.:BCC4303
    CAS No.:1311367-27-7
  • BI-D1870

    Catalog No.:BCC5030
    CAS No.:501437-28-1
  • FMK

    Catalog No.:BCC1580
    CAS No.:821794-92-7

Quality Control of CNX-774

Number of papers citing our products

Chemical structure

CNX-774

3D structure

Chemical Properties of CNX-774

Cas No. 1202759-32-7 SDF Download SDF
PubChem ID 59174579 Appearance Powder
Formula C26H22FN7O3 M.Wt 499.5
Type of Compound N/A Storage Desiccate at -20°C
Solubility DMSO : ≥ 45 mg/mL (90.09 mM)
*"≥" means soluble, but saturation unknown.
Chemical Name 4-[4-[[5-fluoro-4-[3-(prop-2-enoylamino)anilino]pyrimidin-2-yl]amino]phenoxy]-N-methylpyridine-2-carboxamide
SMILES CNC(=O)C1=NC=CC(=C1)OC2=CC=C(C=C2)NC3=NC=C(C(=N3)NC4=CC(=CC=C4)NC(=O)C=C)F
Standard InChIKey VVLHQJDAUIPZFH-UHFFFAOYSA-N
Standard InChI InChI=1S/C26H22FN7O3/c1-3-23(35)31-17-5-4-6-18(13-17)32-24-21(27)15-30-26(34-24)33-16-7-9-19(10-8-16)37-20-11-12-29-22(14-20)25(36)28-2/h3-15H,1H2,2H3,(H,28,36)(H,31,35)(H2,30,32,33,34)
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 CNX-774

DescriptionCNX-774 is a potent, selective, and orally available small molecule inhibitor of Btk (IC50< 1 nM) that forms a ligand-directed covalent bond with Cys-481, a non-conserved amino acid within the active site of the enzyme. IC50 Value: <1 nM [1] Target: Btk Kinase In biochemical assays, CNX-774 has demonstrated potent inhibition of Btk with an IC50 of <1nM in a continuous-read assay. The covalent bonding of CNX-774 to Btk was confirmed by incubating recombinant Btk protein with a 10-fold molar excess of CNX-774 for 1 hour at room temperature and analysis by MALDI-TOF MS. A shift of protein mass corresponding to the molecular weight of CNX-774 confirmed the covalent bonding of CNX-774 to Btk. Digestion of the covalently bonded Btk with pepsin followed by MSMS analysis established the bonding of CNX-774 to Cys-481. Cellular potency as well as prolonged duration of action of CNX-774 was demonstrated in Ramos cells by using a biotinylated covalent probe that targets the same Cysteine residue as CNX-774. CNX-774 was found to be >90% extractable after 2 hrs of incubation in both rat and human whole blood. These results demonstrate that CNX-774 has potent inhibitory activity towards the intended target, Btk, while achieving remarkable specificity in a variety of assays designed to assess off-target reactivity towards abundant cellular thiols and blood proteins.

References:
[1]. Akinleye A, et al. Ibrutinib and novel BTK inhibitors in clinical development. J Hematol Oncol. 2013 Aug 19;6:59. [2]. In Vitro Reactivity Assessment of Covalent Drugs Targeting Bruton's Tyrosine Kinase

CNX-774 Dilution Calculator

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

calculate

CNX-774 Molarity Calculator

Mass
=
Concentration
x
Volume
x
MW*
 
 
 
g/mol

calculate

Preparing Stock Solutions of CNX-774

1 mg 5 mg 10 mg 20 mg 25 mg
1 mM 2.002 mL 10.01 mL 20.02 mL 40.04 mL 50.0501 mL
5 mM 0.4004 mL 2.002 mL 4.004 mL 8.008 mL 10.01 mL
10 mM 0.2002 mL 1.001 mL 2.002 mL 4.004 mL 5.005 mL
50 mM 0.04 mL 0.2002 mL 0.4004 mL 0.8008 mL 1.001 mL
100 mM 0.02 mL 0.1001 mL 0.2002 mL 0.4004 mL 0.5005 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 CNX-774

CNX-774 is an orally active and selective inhibitor of BTK with IC50 value of <1 nM.

Bruton’s tyrosine kinase (BTK) is an important enzyme in the B-cell antigen receptor (BCR) signaling pathway and also plays an important role in mast cell activation and B cell maturation.

CNX-774 is an orally active, irreversible and selective BTK inhibitor with IC50 value of <1 nM. CNX-774 formed covalent bond with the Cys481 residue within the ATP binding site of BTK. In cellular assays, CNX-774 inhibited BTK with IC50 values of 1-10 nM [1].

Reference:
[1].  Akinleye A, Chen Y, Mukhi N, et al. Ibrutinib and novel BTK inhibitors in clinical development. J Hematol Oncol, 2013, 6: 59.

Featured Products
New Products
 

References on CNX-774

BTK inhibition is a potent approach to block IgE-mediated histamine release in human basophils.[Pubmed:28328081]

Allergy. 2017 Nov;72(11):1666-1676.

BACKGROUND: Recent data suggest that Bruton's tyrosine kinase (BTK) is an emerging therapeutic target in IgE receptor (IgER)-cross-linked basophils. METHODS: We examined the effects of four BTK inhibitors (ibrutinib, dasatinib, AVL-292, and CNX-774) on IgE-dependent activation and histamine release in blood basophils obtained from allergic patients (n=11) and nonallergic donors (n=5). In addition, we examined the effects of these drugs on the growth of the human basophil cell line KU812 and the human mast cell line HMC-1. RESULTS: All four BTK blockers were found to inhibit anti-IgE-induced histamine release from basophils in nonallergic subjects and allergen-induced histamine liberation from basophils in allergic donors. Drug effects on allergen-induced histamine release were dose dependent, with IC50 values ranging between 0.001 and 0.5 mumol/L, and the following rank order of potency: ibrutinib>AVL-292>dasatinib>CNX-774. The basophil-targeting effect of ibrutinib was confirmed by demonstrating that IgE-dependent histamine release in ex vivo blood basophils is largely suppressed in a leukemia patient treated with ibrutinib. Dasatinib and ibrutinib were also found to counteract anti-IgE-induced and allergen-induced upregulation of CD13, CD63, CD164, and CD203c on basophils, whereas AVL-292 and CNX-774 showed no significant effects. Whereas dasatinib and CNX-774 were found to inhibit the growth of HMC-1 cells and KU812 cells, no substantial effects were seen with ibrutinib or AVL-292. CONCLUSIONS: BTK-targeting drugs are potent inhibitors of IgE-dependent histamine release in human basophils. The clinical value of BTK inhibition in the context of allergic diseases remains to be determined.

Ibrutinib and novel BTK inhibitors in clinical development.[Pubmed:23958373]

J Hematol Oncol. 2013 Aug 19;6:59.

Small molecule inhibitors targeting dysregulated pathways (RAS/RAF/MEK, PI3K/AKT/mTOR, JAK/STAT) have significantly improved clinical outcomes in cancer patients. Recently Bruton's tyrosine kinase (BTK), a crucial terminal kinase enzyme in the B-cell antigen receptor (BCR) signaling pathway, has emerged as an attractive target for therapeutic intervention in human malignancies and autoimmune disorders. Ibrutinib, a novel first-in-human BTK-inhibitor, has demonstrated clinical effectiveness and tolerability in early clinical trials and has progressed into phase III trials. However, additional research is necessary to identify the optimal dosing schedule, as well as patients most likely to benefit from BTK inhibition. This review summarizes preclinical and clinical development of ibrutinib and other novel BTK inhibitors (GDC-0834, CGI-560, CGI-1746, HM-71224, CC-292, and ONO-4059, CNX-774, LFM-A13) in the treatment of B-cell malignancies and autoimmune disorders.

Description

CNX-774 is a potent, selective, and orally available small molecule inhibitor of Btk (IC50< 1 nM) that forms a ligand-directed covalent bond with Cys-481, a non-conserved amino acid within the active site of the enzyme.

Keywords:

CNX-774,1202759-32-7,Natural Products,BTK, buy CNX-774 , CNX-774 supplier , purchase CNX-774 , CNX-774 cost , CNX-774 manufacturer , order CNX-774 , high purity CNX-774

Online Inquiry for:

      Fill out the information below

      • Size:Qty: - +

      * Required Fields

                                      Result: