Ferroptosis-centered Drug Response Information
General Information of the Drug (ID: ferrodrug0352)
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GAP 27
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| Synonyms |
GAP 27; 198284-64-9; Gap27; Connexin mimetic peptide; Connexin43 mimetic peptide; DTXSID80432769; MFCD03456920; AKOS024456622; H-Ser-Arg-Pro-Thr-Glu-Lys-Thr-Ile-Phe-Ile-Ile-OH
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| Structure |
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3D MOL
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| Formula |
C60H101N15O17
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| IUPAC Name |
(2S,3S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S,3R)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-amino-3-hydroxypropanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxybutanoyl]amino]-4-carboxybutanoyl]amino]hexanoyl]amino]-3-hydroxybutanoyl]amino]-3-methylpentanoyl]amino]-3-phenylpropanoyl]amino]-3-methylpentanoyl]amino]-3-methylpentanoic acid
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| Canonical SMILES |
CCC(C)C(C(=O)NC(C(C)CC)C(=O)O)NC(=O)C(CC1=CC=CC=C1)NC(=O)C(C(C)CC)NC(=O)C(C(C)O)NC(=O)C(CCCCN)NC(=O)C(CCC(=O)O)NC(=O)C(C(C)O)NC(=O)C2CCCN2C(=O)C(CCCN=C(N)N)NC(=O)C(CO)N
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| InChI |
InChI=1S/C60H101N15O17/c1-9-31(4)44(54(86)69-41(29-36-19-13-12-14-20-36)52(84)70-45(32(5)10-2)55(87)72-46(59(91)92)33(6)11-3)71-57(89)48(35(8)78)73-51(83)38(21-15-16-26-61)66-50(82)39(24-25-43(79)80)67-56(88)47(34(7)77)74-53(85)42-23-18-28-75(42)58(90)40(22-17-27-65-60(63)64)68-49(81)37(62)30-76/h12-14,19-20,31-35,37-42,44-48,76-78H,9-11,15-18,21-30,61-62H2,1-8H3,(H,66,82)(H,67,88)(H,68,81)(H,69,86)(H,70,84)(H,71,89)(H,72,87)(H,73,83)(H,74,85)(H,79,80)(H,91,92)(H4,63,64,65)/t31-,32-,33-,34+,35+,37-,38-,39-,40-,41-,42-,44-,45-,46-,47-,48-/m0/s1
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| InChIKey |
SXRAPDIXXYFGJG-MDAHIHQXSA-N
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| PubChem CID | |||||
Full List of Ferroptosis Target Related to This Drug
Cystine/glutamate transporter (SLC7A11)
| In total 1 item(s) under this Target | |||||
| Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target | [1] | ||||
| Target for Ferroptosis | Suppressor | ||||
| Responsed Disease | Acute kidney failure | ICD-11: GB60 | |||
| Responsed Regulator | Gap junction alpha-1 protein (GJA1) | Driver | |||
| Pathway Response | Fatty acid metabolism | hsa01212 | |||
| Glutathione metabolism | hsa00480 | ||||
| Apoptosis | hsa04210 | ||||
| Cell Process | Cell ferroptosis | ||||
| Cell apoptosis | |||||
| In Vitro Model | HK-2 cells | Normal | Homo sapiens | CVCL_0302 | |
| In Vivo Model |
Thirty-two male C57BL/6 mice (20 ± 2) g (Beijing Weitonglihua Experimental Animal Technology Co., Ltd.) were bred in individually ventilated cages (IVC) at SPF conditions, kept on a 12 h light/dark cycle, relative humidity conditions (40-70%) and controlled temperature (24 ± 2 ). After one-week acclimation mice were divided randomly into four groups: control group, cisplatin group (20 mg/kg cisplatin dissolved in saline), cisplatin + Fer-1 group (5 mg/kg Fer-1 dissolved in DMSO), and cisplatin + gap27 group (35 ug/kg gap27 dissolved in DMSO). There were eight animals in each group and 20 mg/kg cisplatin was given to each animal once by intraperitoneal injection except mice in the control group. Fer-1 and gap27 was administered 1 h before the injection of cisplatin.
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| Response regulation | Downregulation of Cx43 expression by gap27 reduced acute kidney injury in the animal model by inhibiting cisplatin-induced ferroptosis. Therefore, our results indicated that downregulation of Cx43 can inhibit ferroptosis by restoring the level of SLC7A11 in the system xctransporter and alleviate cisplatin-induced acute kidney injury. | ||||