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.
- 1. Michaela T. Reichmann, Liku B Tezera, et al. "Integrated transcriptomic analysis of human tuberculosis granulomas and a biomimetic model identifies therapeutic targets." J Clin Invest. 2021 Aug 2;131(15):e148136. PMID:34128839
- 2. Chen Y, Yu Y, et al. "Bradykinin promotes migration and invasion of hepatocellular carcinoma cells through TRPM7 and MMP2." Exp Cell Res. 2016 Sep 29. PMID:27693494
| Storage | Store at -20°C |
| M.Wt | 431.53 |
| Cas No. | 897016-82-9 |
| Formula | C26H29N3O3 |
| Solubility | insoluble in H2O; ≥121 mg/mL in DMSO; ≥2.44 mg/mL in EtOH with gentle warming and ultrasonic |
| Chemical Name | N-benzyl-2-[5-[4-(2-morpholin-4-ylethoxy)phenyl]pyridin-2-yl]acetamide |
| SDF | Download SDF |
| Canonical SMILES | C1COCCN1CCOC2=CC=C(C=C2)C3=CN=C(C=C3)CC(=O)NCC4=CC=CC=C4 |
| 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. |
| Cell experiment [1-3]: | |
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Cell lines |
HCC cell lines Huh7, PLC/PRF/5, Hep3B, and HepG2 |
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Preparation method |
The solubility of this compound in DMSO is >121mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
6,564 to 0.012 nM, 3 days |
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Applications |
KX2-391 showed dose-response curves against all four HCC cell lines Huh7, PLC/PRF/5, Hep3B, and HepG2 with the GI50 of 9 nM, 13 nM, 26 nM, and 60 nM, respectively. In NIH3T3/c-Src527F and SYF/c-Src527F cells, KX2-391 inhibited cell growth with the GI50 of 23 nM and 39 nM, respectively. KXO1 (10-30 nM) could halve proliferation rates (GI50) of a panel of human cancer cell lines known to have activated levels of SFK- such as HT-29 human colon cancer cells, as well as NIH3T3/c-Src527F cells. KXO1 inhibited anchorage-independent growth of HT-29 and 3T3/c-Src527F cells. |
| Animal experiment [3]: | |
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Animal models |
nude mice bearing 50 cc HT-29 tumors |
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Dosage form |
Oral administration, 5 mg/kg bid |
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Application |
Treatment of nude mice bearing 50 cc HT-29 tumors with 5 mg/kg KXO1 bid p.o. resulted in a 70% reduction tumor growth, with no significant toxicity to the host as determined by weight loss. |
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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. |
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References: [1]. Lau G M, Lau G M, Yu G L, et al. Expression of Src and FAK in hepatocellular carcinoma and the effect of Src inhibitors on hepatocellular carcinoma in vitro[J]. Digestive diseases and sciences, 2009, 54(7): 1465-1474. [2]. Fallah-Tafti A, Foroumadi A, Tiwari R, et al. Thiazolyl N-benzyl-substituted acetamide derivatives: synthesis, Src kinase inhibitory and anticancer activities[J]. European journal of medicinal chemistry, 2011, 46(10): 4853-4858. [3]. Bu Y, Gao L, Smolinski M, et al. KXO1 (KX2-391), a Src-family kinase inhibitor targeting the peptide-binding domain, suppresses oncogenic proliferation in vitro and in vivo[J]. 2008. |
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| 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) | ||
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