Ferroptosis-centered Drug Response Information

General Information of the Drug (ID: ferrodrug0314)
Name
CyPPA
Synonyms
CyPPA; 73029-73-9; N-cyclohexyl-2-(3,5-dimethyl-1H-pyrazol-1-yl)-6-methylpyrimidin-4-amine; cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine; CHEMBL453730; N-cyclohexyl-2-(3,5-dimethylpyrazol-1-yl)-6-methylpyrimidin-4-amine; N-Cyclohexyl-N-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-4-pyrimidinamine; C16H23N5; GTPL2323; SCHEMBL3233745; DTXSID20358676; USEMRPYUFJNFQN-UHFFFAOYSA-N; HMS3262M15; HMS3742C19; AMY18135; EX-A5595; Tox21_500707; BDBM50275157; CyPPA, >=98% (HPLC), solid; HB1044; STK052676; AKOS015999173; CCG-222011; CS-W012225; HY-W011509; LP00707; SDCCGSBI-0633746.P001; NCGC00186022-01; NCGC00186022-05; NCGC00261392-01; MS-24068; F85618; Q27076959

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Status
Investigative
Drug Type
Small molecular drug
Structure
Formula
C16H23N5
IUPAC Name
N-cyclohexyl-2-(3,5-dimethylpyrazol-1-yl)-6-methylpyrimidin-4-amine
Canonical SMILES
CC1=CC(=NC(=N1)N2C(=CC(=N2)C)C)NC3CCCCC3
InChI
InChI=1S/C16H23N5/c1-11-10-15(18-14-7-5-4-6-8-14)19-16(17-11)21-13(3)9-12(2)20-21/h9-10,14H,4-8H2,1-3H3,(H,17,18,19)
InChIKey
USEMRPYUFJNFQN-UHFFFAOYSA-N
PubChem CID
909822
TTD Drug ID
D00DIF
Full List of Ferroptosis Target Related to This Drug
Unspecific Target
In total 1 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [1]
Responsed Disease Health ICD-11: N.A.
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Gluconeogenesis hsa00010
Cell Process Cell ferroptosis
In Vitro Model HT22 cells Normal Mus musculus CVCL_0321
In Vivo Model
The C. elegans strain N2 was grown on NGM plates and on OP50 bacteria as a food source. For the lactate measurement, the nematodes were synchronized by bleaching with NaOH/NaClO and grown on NGM plates containing OP50 and either DMSO, 100 uM CyPPA or 250 uM CyPPA for 4 days. To determine lactate levels, the lactate assay kit was used (Sigma-Aldrich, MAK064). Briefly, worms were collected and washed to remove OP50. The worm pellet was snap-frozen, resuspended in lactate assay buffer and sonicated to break the cuticle. After centrifugation at 13000 rpm for 10 min, the supernatant was applied to a 10 kDa MWCO filter and centrifuged for 60 min at 13000 rpm to remove insoluble material.

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Response regulation CyPPA rescued the neuronal cells from ferroptosis, while scavenging mitochondrial ROS and inhibiting glycolysis reduced its protection. Furthermore, SK channel activation increased survival of C. elegans challenged with mitochondrial toxins.
References
Ref 1 SK channel-mediated metabolic escape to glycolysis inhibits ferroptosis and supports stress resistance in C. elegans. Cell Death Dis. 2020 Apr 23;11(4):263. doi: 10.1038/s41419-020-2458-4.