KX2-391Src inhibitor,highly selective CAS# 897016-82-9 |
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Quality Control & MSDS
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Chemical structure
3D structure
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. |
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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. |
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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. |
Description | KX2-391 is an inhibitor of Src (peptidomimetic class) with GI50 value of 9-60 nM in cancer cell lines. | ||||||
Targets | Src (HuH7) | Src (PLC/PRF/5) | Src (Hep 3B) | Src (Hep G2) | |||
IC50 | 9 nM(GI50) | 13 nM(GI50) | 26 nM(GI50) | 60 nM(GI50) |
KX2-391 Dilution Calculator
KX2-391 Molarity Calculator
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. |
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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.
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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.