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Phortress is a 2-(4-aminophenyl)benzothiazole derivative that is currently in phase-1 [[clinical trial]]s. It was developed from compound CJM 126, which was previously identified in a [[kinase inhibitor]] discovery programme. In order to improve this drug's anti-tumour activity, CJM 126 was derivatised by methylation on its phenolic ring, producing 2-(4-Amino-3-methylphenyl)benzothiazole (DF 203). DF 203 suffered from [[metabolism]] at higher concentrations, so a [[fluorine]] atom was substituted on the [[benzothiazole]] group. Finally, to improve its [[solubility]] it was conjugated to [[lysine]] forming the final |
Phortress is a 2-(4-aminophenyl)benzothiazole derivative that is currently in phase-1 [[clinical trial]]s. It was developed from compound CJM 126, which was previously identified in a [[kinase inhibitor]] discovery programme. In order to improve this drug's anti-tumour activity, CJM 126 was derivatised by methylation on its phenolic ring, producing 2-(4-Amino-3-methylphenyl)benzothiazole (DF 203). DF 203 suffered from [[metabolism]] at higher concentrations, so a [[fluorine]] atom was substituted on the [[benzothiazole]] group (producing 5F 203). Finally, to improve its [[solubility]] it was conjugated to [[lysine]], forming the final lysylamide [[prodrug]] for clinical assessment. |
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In cells, the drug is broken down by hydrolysis of the lysylamide group, producing the active drug 5F 203. This binds to the [[aryl hydrocarbon receptor]], activating [[gene transcription|transcription]] of the [[Cytochrome P450, family 1, member A1|''cyp1a1'']] [[gene]]. The enzyme produced from this gene further breaks down 5F 203 into reactive species, which lead to DNA damage and cell death. |
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[[File:CJM-126.png|thumb|CJM-126]] |
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[[File:CJM126 DF203 5F203.png|thumb|262px|CJM 126, DF 203 and 5F 203]] |
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Revision as of 14:18, 8 March 2018
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| Clinical data | |
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| Trade names | Phortress |
| Identifiers | |
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| PubChem CID | |
| Chemical and physical data | |
| Formula | C20H24ClFN4OS |
| Molar mass | 422.947 g/mol g·mol−1 |
Phortress is a 2-(4-aminophenyl)benzothiazole derivative that is currently in phase-1 clinical trials. It was developed from compound CJM 126, which was previously identified in a kinase inhibitor discovery programme. In order to improve this drug's anti-tumour activity, CJM 126 was derivatised by methylation on its phenolic ring, producing 2-(4-Amino-3-methylphenyl)benzothiazole (DF 203). DF 203 suffered from metabolism at higher concentrations, so a fluorine atom was substituted on the benzothiazole group (producing 5F 203). Finally, to improve its solubility it was conjugated to lysine, forming the final lysylamide prodrug for clinical assessment.
In cells, the drug is broken down by hydrolysis of the lysylamide group, producing the active drug 5F 203. This binds to the aryl hydrocarbon receptor, activating transcription of the cyp1a1 gene. The enzyme produced from this gene further breaks down 5F 203 into reactive species, which lead to DNA damage and cell death.
