KX1-004 is a novel and potent small molecule inhibitor of Src-protein tyrosine kinase that can be used to reduce cisplatin ototoxicity while preserving its antitumor effect. KX1-004 has also been used to protect the cochlea from hazardous noise. Animals treated with KX1-004 had from 10 to 20 dB less temporary threshold shift at day 1 and an average 10 dB less permanent threshold shift by day 21 when compared to control saline treated animals. There were no significant side effects (i.e.: appetite loss, weight loss, lethargy, etc.) related to the drug treatments. KX1-004 produced at least as much protection as L-NAC, but at a significantly lower concentration.
理化性质和储存条件
| Molecular Weight (MW) | 284.10 |
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| Formula | C16H13FN2O2 |
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| CAS No. | 518058-84-9 |
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| Storage | -20℃ for 3 years in powder form |
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| -80℃ for 2 years in solvent |
| Solubility (In vitro) | DMSO: ≥ 40 mg/mL |
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| Water: <1 mg/mL |
| Ethanol: N/A |
| SMILES Code | O=C(C(N1)=CC2=C1C=CC(F)=C2)NCC3=CC=CC(O)=C3 |
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| Synonyms | KX1004; KX 1004; KX1-004. |
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实验参考方法
| In Vitro | In vitro activity: KX1-004 is a novel and potent small molecule inhibitor of Src-protein tyrosine kinase that can be used to reduce cisplatin ototoxicity while preserving its antitumor effect. KX1-004 has also been used to protect the cochlea from hazardous noise. Animals treated with KX1-004 had from 10 to 20 dB less temporary threshold shift at day 1 and an average 10 dB less permanent threshold shift by day 21 when compared to control saline treated animals. There were no significant side effects (i.e.: appetite loss, weight loss, lethargy, etc.) related to the drug treatments. KX1-004 produced at least as much protection as L-NAC, but at a significantly lower concentration.
Kinase Assay: KX1-004 is a potent small molecule inhibitor of Src-PTK as a potential protective drug for NIHL. |
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| In Vivo | Src-PTK inhibitor KX1-004, KX1-005 and KX1-174 as potential protective drugs for NIHL. Chinchillas were used as subjects. A 30 microl drop of one of the Src inhibitors was placed on the round window membrane of the anesthetized chinchilla; the vehicle (DMSO and buffered saline) alone was placed on the other ear. After the drug application, the middle ear was sutured and the subjects were exposed to noise. Hearing was measured before and several times after the noise exposure and treatment using evoked responses. At 20 days post-exposure, the animals were anesthetized their cochleae extracted and cochleograms were constructed. All three Src inhibitors provided protection from a 4 h, 4 kHz octave band noise at 106 dB. The most effective drug, KX1-004 was further evaluated by repeating the exposure with different doses, as well as, substituting an impulse noise exposure. LNAC was delivered intraperitoneally at a dose of 325 mg/kg while KX1-004 was administered subcutaneously at a dose of 50 mg/kg. The noise exposure consisted of a 4 kHz octave band of noise at 100 dB SPL for 6 hours/day for 4 days. The drugs were administered once each day, 30 minutes prior to the onset of the noise exposure. The animals' hearing was estimated using the evoked response records from surgically-implanted chronic electrodes in the inferior colliculi. Animals treated with LNAC and KX1-004 had from 10 to 20 dB less temporary threshold shift at day 1 and an average 10 dB less permanent threshold shift by day 21 when compared to control saline treated animals. |
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| Animal model | N/A |
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| Formulation & Dosage | Administered subcutaneously at a dose of 50 mg/kg |
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| References | Noise Health. 2005 Oct-Dec;7(29):24-30; Hear Res. 2005 Oct;208(1-2):14-25. |
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