KX2-391

Src inhibitor,highly selective CAS# 897016-82-9

KX2-391

Catalog No. BCC5080----Order now to get a substantial discount!

Product Name & Size Price Stock
KX2-391: 5mg $69 In Stock
KX2-391: 10mg Please Inquire In Stock
KX2-391: 20mg Please Inquire Please Inquire
KX2-391: 50mg Please Inquire Please Inquire
KX2-391: 100mg Please Inquire Please Inquire
KX2-391: 200mg Please Inquire Please Inquire
KX2-391: 500mg Please Inquire Please Inquire
KX2-391: 1000mg Please Inquire Please Inquire
Related Products

Quality Control of KX2-391

Number of papers citing our products

Chemical structure

KX2-391

3D structure

Chemical Properties of KX2-391

Cas No. 897016-82-9 SDF Download SDF
PubChem ID 23635314 Appearance Powder
Formula C26H29N3O3 M.Wt 431.53
Type of Compound N/A Storage Desiccate at -20°C
Synonyms KX-01
Solubility DMSO : 41.67 mg/mL (96.56 mM; Need ultrasonic)
Chemical Name N-benzyl-2-[5-[4-(2-morpholin-4-ylethoxy)phenyl]pyridin-2-yl]acetamide
SMILES C1COCCN1CCOC2=CC=C(C=C2)C3=CN=C(C=C3)CC(=O)NCC4=CC=CC=C4
Standard InChIKey HUNGUWOZPQBXGX-UHFFFAOYSA-N
Standard InChI InChI=1S/C26H29N3O3/c30-26(28-19-21-4-2-1-3-5-21)18-24-9-6-23(20-27-24)22-7-10-25(11-8-22)32-17-14-29-12-15-31-16-13-29/h1-11,20H,12-19H2,(H,28,30)
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 KX2-391

DescriptionKX2-391 is an inhibitor of Src (peptidomimetic class) with GI50 value of 9-60 nM in cancer cell lines.
TargetsSrc (HuH7)Src (PLC/PRF/5)Src (Hep 3B)Src (Hep G2)    
IC509 nM(GI50)13 nM(GI50)26 nM(GI50)60 nM(GI50)    

Protocol

Cell Assay [1]
Liver cell lines including Huh7, PLC/PRF/5, Hep3B, and HepG2 are routinely cultured and maintained in basal medium containing 2% fetal bovine serum (FBS) at 37°C and 5% CO2. Cells are seeded at 4.0×103/190 μL and 8.0×103/190 μL per well of 96-well plate in basal medium containing 1.5% FBS. These are cultured overnight at 37°C and 5% CO2 prior to the addition of KX2-391, at concentrations ranging from 6,564 to 0.012 nM in triplicates. Treated cells are incubated for 3 days. Ten μLs of 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide (MTT) solution (5 mg/mL) is then added to each well on day 3 and cells incubated for 4 hours. The formazan product is dissolved with 10% SDS in dilute HCl. Optical density at 570 nm is measured. For comparison of activity and potency, parallel experiments are performed using KX2-391. Growth inhibition curves, 50% inhibition concentration (GI50), and 80% inhibition concentration (GI80) are determined using GraphPad Prism 5 statistical software. Data are normalized to represent percentage of maximum response as well as reported in optical density at wavelength of 570 nm (OD570) signal format[1].

References:
[1]. Lau GM, et al. Expression of Src and FAK in hepatocellular carcinoma and the effect of Src inhibitors on hepatocellular carcinoma in vitro. Dig Dis Sci, 2009, 54(7), 1465-1474. [2]. Fallah-Tafti A, et al. Thiazolyl N-benzyl-substituted acetamide derivatives: synthesis, Src kinase inhibitory and anticancer activities. Eur J Med Chem, 2011, 46(10), 4853-4858.

KX2-391 Dilution Calculator

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

calculate

KX2-391 Molarity Calculator

Mass
=
Concentration
x
Volume
x
MW*
 
 
 
g/mol

calculate

Preparing Stock Solutions of KX2-391

1 mg 5 mg 10 mg 20 mg 25 mg
1 mM 2.3173 mL 11.5867 mL 23.1734 mL 46.3467 mL 57.9334 mL
5 mM 0.4635 mL 2.3173 mL 4.6347 mL 9.2693 mL 11.5867 mL
10 mM 0.2317 mL 1.1587 mL 2.3173 mL 4.6347 mL 5.7933 mL
50 mM 0.0463 mL 0.2317 mL 0.4635 mL 0.9269 mL 1.1587 mL
100 mM 0.0232 mL 0.1159 mL 0.2317 mL 0.4635 mL 0.5793 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 KX2-391

KX2-391 is a highly selective inhibitor of Src kinase with IC50 value of 20nM [1].

KX2-391 is a non-ATP competitive inhibitor of Src. It is the first inhibitor that targets Src kinase within the substrate binding site. KX2-391 inhibits Src catalyzed trans-phosphorylation of FAK, Shc, paxillin as well as Src kinase autophosphorylation. KX2-391 has no effects on PDGFR, EGFR, JAK1, JAK2 and Lck demonstrating it as a selective inhibitor. It is also found to be an inhibitor of tubulin polymerization through binding to the unique confirmation on heterodimeric tubulin. In cellular assays, KX2-391 shows growth inhibition in NIH3T3/c-Src527F cells and SYF/c-Src527F cells with GI50 values of 23nM and 39nM, respectively [1, 2].

Since Src acts as a regulator in cell proliferation survival, motility and invasiveness, KX2-391 is potent against a variety of solid tumors and many leukemia tumors. It is shown to inhibit primary tumor growth and to suppress metastasis [2].

References:
[1] Fallah-Tafti A, Foroumadi A, Tiwari R, et al. Thiazolyl N-benzyl-substituted acetamide derivatives: Synthesis, Src kinase inhibitory and anticancer activities. European journal of medicinal chemistry, 2011, 46(10): 4853-4858.
[2] Naing A, Cohen R, Dy G K, et al. A phase I trial of KX2-391, a novel non-ATP competitive substrate-pocket-directed SRC inhibitor, in patients with advanced malignancies. Investigational new drugs, 2013, 31(4): 967-973.

Featured Products
New Products
 

References on KX2-391

A phase 2 study of KX2-391, an oral inhibitor of Src kinase and tubulin polymerization, in men with bone-metastatic castration-resistant prostate cancer.[Pubmed:23314737]

Cancer Chemother Pharmacol. 2013 Apr;71(4):883-92.

PURPOSE: KX2-391 is an oral non-ATP-competitive inhibitor of Src kinase and tubulin polymerization. In phase 1 trials, prostate-specific antigen (PSA) declines were seen in patients with advanced prostate cancer. We conducted a single-arm phase 2 study evaluating KX2-391 in men with chemotherapy-naive bone-metastatic castration-resistant prostate cancer (CRPC). METHODS: We treated 31 patients with oral KX2-391 (40 mg twice-daily) until disease progression or unacceptable toxicity. The primary endpoint was 24-week progression-free survival (PFS); a 50 % success rate was pre-defined as clinically significant. Secondary endpoints included PSA progression-free survival (PPFS) and PSA response rates. Exploratory outcomes included pharmacokinetic studies, circulating tumor cell (CTC) enumeration, and analysis of markers of bone resorption [urinary N-telopeptide (uNTx); C-telopeptide (CTx)] and formation [bone alkaline phosphatase (BAP); osteocalcin]. RESULTS: The trial closed early after accrual of 31 patients, due to a pre-specified futility rule. PFS at 24 weeks was 8 %, and median PFS was 18.6 weeks. The PSA response rate (>/= 30 % decline) was 10 %, and median PPFS was 5.0 weeks. Additionally, 18 % of men with unfavorable (>/= 5) CTCs at baseline converted to favorable (<5) CTCs with treatment. The proportion of men with declines in bone turnover markers was 32 % for uNTx, 21 % for CTx, 10 % for BAP, and 25 % for osteocalcin. In pharmacokinetic studies, median C max was 61 (range 16-129) ng/mL, and median AUC was 156 (35-348) ng h/mL. Common toxicities included hepatic derangements, myelosuppression, fatigue, nausea, and constipation. CONCLUSION: KX2-391 dosed at 40 mg twice-daily lacks antitumor activity in men with CRPC, but has modest effects on bone turnover markers. Because a C max of >/=142 ng/mL is required for tubulin polymerization inhibition (defined from preclinical studies), higher once-daily dosing will be used in future trials.

A phase I trial of KX2-391, a novel non-ATP competitive substrate-pocket- directed SRC inhibitor, in patients with advanced malignancies.[Pubmed:23361621]

Invest New Drugs. 2013 Aug;31(4):967-73.

BACKGROUND: Src kinase is central to tumor cell proliferation, apoptosis, and metastasis. KX2-391 is a synthetic, orally bioavailable small molecule inhibitor of Src tyrosine kinase (TK) signaling and tubulin polymerization. This compound is distinct from other Src kinase inhibitors by targeting the peptide substrate rather than the ATP binding site; the binding site on hetero-dimeric tubulin is novel and distinct from the taxanes and other known tubulin inhibitors. METHODS: This multicenter Phase I trial utilized a 4 + 2 study design to determine the maximum tolerated dose (MTD), safety, and pharmacokinetics (PK) of KX2-391 in patients with refractory solid tumors. RESULTS: Forty-four (44) patients (18 M, 26 F; median age, 59) were enrolled in 9 dose cohorts. Dose-limiting toxicities, all reversible within 7 days, occurred in 7 patients and consisted of elevated AST (n = 4), ALT (n = 2), neutropenia (n = 1), thrombocytopenia (n = 1), failure to thrive (n = 1) and anorexia (n = 1). The MTD is 40 mg BID continuously. Eleven patients had stable disease for >/= 4 months, including patients with ovarian, carcinoid, papillary thyroid, prostate, pancreas and head and neck cancer. Patients with prostate and pancreatic cancer also had significant biomarker decreases (PSA, 205 ng/mL to 39 ng/mL; CA19-9, 38,838 U/mL to 267 U/mL). The ovarian cancer patient has had stable disease > 12 months. KX2-391 was orally available, rapidly absorbed, and exposure was proportional to dose across the range investigated. CONCLUSIONS: KX2-391 has a favorable pharmacokinetic profile, is well tolerated, demonstrates preliminary evidence of biologic activity, and warrants further evaluation in Phase II trials.

Description

Tirbanibulin (KX2-391) is an inhibitor of Src that targets the peptide substrate site of Src, with GI50 of 9-60 nM in cancer cell lines.

Keywords:

KX2-391,897016-82-9,KX-01,Natural Products,Src, buy KX2-391 , KX2-391 supplier , purchase KX2-391 , KX2-391 cost , KX2-391 manufacturer , order KX2-391 , high purity KX2-391

Online Inquiry for:

      Fill out the information below

      • Size:Qty: - +

      * Required Fields

                                      Result: