====== CFI-400945 25μM R08 exp469 ====== ==== Mechanism of Action ==== Inhibits PLK4, blocks centriole duplication, induces mitotic defects and cell death * **Class / Subclass 1:** Signal Transduction / Kinase Inhibitor * **Class / Subclass 2:** Cell Cycle / Mitotic Inhibitor ==== Technical Notes ==== * **PubChem Name:** %%CFI-400945 free base%% * **Synonyms:** N/A * **CAS #:** 1338806-73-7 * **PubChem CID:** [[https://pubchem.ncbi.nlm.nih.gov/compound/58486178|58486178]] * **IUPAC:** %%(2'S,3R)-2'-[3-[(E)-2-[4-[[(2S,6R)-2,6-dimethylmorpholin-4-yl]methyl]phenyl]ethenyl]-1H-indazol-6-yl]-5-methoxyspiro[1H-indole-3,1'-cyclopropane]-2-one%% * **INCHI Name:** InChI=1S/C33H34N4O3/c1-20-17-37(18-21(2)40-20)19-23-6-4-22(5-7-23)8-12-29-26-11-9-24(14-31(26)36-35-29)28-16-33(28)27-15-25(39-3)10-13-30(27)34-32(33)38/h4-15,20-21,28H,16-19H2,1-3H3,(H,34,38)(H,35,36)/b12-8+/t20-,21+,28-,33-/m0/s1 * **INCHI Key:** DADASRPKWOGKCU-FVTQAUBDSA-N * **Molecular Weight:** 534.6 * **Canonical SMILES:** CC1CN(CC(O1)C)CC2=CC=C(C=C2)C=CC3=NNC4=C3C=CC(=C4)C5CC56C7=C(C=CC(=C7)OC)NC6=O * **Isomeric SMILES:** C[C@@H]1CN(C[C@@H](O1)C)CC2=CC=C(C=C2)/C=C/C3=NNC4=C3C=CC(=C4)[C@@H]5C[C@]56C7=C(C=CC(=C7)OC)NC6=O * **Molecular Formula:** C33H34N4O3 {{:chemogenomics:structures:chem-0278.svg?nolink}} * **Supplier Name:** Med Chem Express * **Catalog #:** HY-12300 * **Lot #:** 23771 * **HRMS (ESI-TOF) m/z:** (M+H)+ Calcd for C33H34N4O3 535.27037; found 535.27075 * **Platform ID:** CFI400945 * **Min:** -8.6037; **Max:** 76.6696 {{:chemogenomics:dose_response:dr_607.png?nolink&500 |}} \\ \\ \\ \\ |< 300px 100px 200px >| ^ IC ^ Concentration (µM) ^ | IC10 |19.9700 | | IC20 |24.7200 | | IC30 |28.4900 | | IC40 |32.0000 | | IC50 |35.6100 | | IC60 |39.6200 | | IC70 |44.5100 | | IC80 |51.3000 | | IC90 |63.5100 | \\ ==== Screen Summary ==== * **Round**: 08 * **Dose**: 25µM * **Days of incubation**: 8 * **Doublings**: -0.4 * **Numbers of reads**: 14411620 ==== Screen Results ==== ^Sensitive/Resistant hits (FDR<0.05)^CRANKS^Score Plot^Top 30 Genes^Screen Similarity^Top 30 Sensitive GO terms^Top 30 Resistant GO terms^ |29/0|[[https://files.tyerslab.com/files/public/chemogenomics/cranks/CFI-400945_25uM_Round-8_exp469.txt|Scores]]|||||| {{:chemogenomics:cranks_plots:exp469.png?nolink}} ^Gene^CRANKS Score^FDR^ |[[:human_genes:S:SCYL1|SCYL1]]|-3.97|<0.01| |[[:human_genes:G:GPR107|GPR107]]|-3.67|<0.01| |[[:human_genes:G:GOLGA8H|GOLGA8H]]|-3.43|0.04| |[[:human_genes:S:SLC5A3|SLC5A3]]|-3.39|<0.01| |[[:human_genes:O:OSBPL9|OSBPL9]]|-3.35|<0.01| |[[:human_genes:T:TMEM167B|TMEM167B]]|-3.19|<0.01| |[[:human_genes:O:OSBPL11|OSBPL11]]|-3.07|<0.01| |[[:human_genes:C:COG7|COG7]]|-3.02|<0.01| |[[:human_genes:P:PCYT1A|PCYT1A]]|-3.00|<0.01| |[[:human_genes:Y:YIPF5|YIPF5]]|-2.99|<0.01| |[[:human_genes:S:SGMS1|SGMS1]]|-2.98|<0.01| |[[:human_genes:C:CYB561D2|CYB561D2]]|-2.94|<0.01| |[[:human_genes:A:ATP6V0A2|ATP6V0A2]]|-2.84|<0.01| |[[:human_genes:C:COPZ1|COPZ1]]|-2.79|<0.01| |[[:human_genes:U:UNC50|UNC50]]|-2.79|<0.01| |[[:human_genes:G:GAGE2A|GAGE2A]]|-2.79|0.23| |[[:human_genes:F:FLVCR1|FLVCR1]]|-2.78|<0.01| |[[:human_genes:S:SART1|SART1]]|-2.77|0.13| |[[:human_genes:A:ARL1|ARL1]]|-2.75|<0.01| |[[:human_genes:Y:YIPF4|YIPF4]]|-2.74|<0.01| |[[:human_genes:A:ARID4B|ARID4B]]|-2.71|0.01| |[[:human_genes:V:VKORC1L1|VKORC1L1]]|-2.63|<0.01| |[[:human_genes:Z:ZBTB7A|ZBTB7A]]|-2.62|0.01| |[[:human_genes:C:COG5|COG5]]|-2.59|0.02| |[[:human_genes:T:TM9SF2|TM9SF2]]|-2.54|0.01| |[[:human_genes:C:COPB2|COPB2]]|-2.50|0.24| |[[:human_genes:G:GOLGA6L1|GOLGA6L1]]|-2.49|0.46| |[[:human_genes:D:DDX3X|DDX3X]]|-2.48|0.02| |[[:human_genes:P:PI4KB|PI4KB]]|-2.47|0.04| |[[:human_genes:Z:ZNF91|ZNF91]]|-2.47|0.02| |[[:human_genes:U:URM1|URM1]]|1.98|0.32| |[[:human_genes:W:WDR77|WDR77]]|1.98|0.38| |[[:human_genes:P:P2RY4|P2RY4]]|1.99|0.32| |[[:human_genes:C:C11orf87|C11orf87]]|2.00|0.32| |[[:human_genes:D:DSCR4|DSCR4]]|2.00|0.32| |[[:human_genes:R:RRAGA|RRAGA]]|2.00|0.33| |[[:human_genes:T:TBC1D16|TBC1D16]]|2.06|0.33| |[[:human_genes:S:SHISA4|SHISA4]]|2.07|0.32| |[[:human_genes:C:CERCAM|CERCAM]]|2.08|0.26| |[[:human_genes:O:ODC1|ODC1]]|2.10|0.26| |[[:human_genes:M:MEAF6|MEAF6]]|2.16|0.33| |[[:human_genes:C:CDH22|CDH22]]|2.17|0.29| |[[:human_genes:G:GEMIN8|GEMIN8]]|2.17|0.33| |[[:human_genes:D:DDX55|DDX55]]|2.20|0.26| |[[:human_genes:A:ALG13|ALG13]]|2.22|0.26| |[[:human_genes:P:PHIP|PHIP]]|2.23|0.15| |[[:human_genes:L:LIN52|LIN52]]|2.31|0.10| |[[:human_genes:M:MRPS5|MRPS5]]|2.33|0.17| |[[:human_genes:E:ENO1|ENO1]]|2.34|0.33| |[[:human_genes:P:PARK2|PARK2]]|2.35|0.09| |[[:human_genes:T:TAMM41|TAMM41]]|2.36|0.09| |[[:human_genes:U:UQCR10|UQCR10]]|2.40|0.09| |[[:human_genes:A:ATP5B|ATP5B]]|2.40|0.09| |[[:human_genes:P:PAXBP1|PAXBP1]]|2.49|0.09| |[[:human_genes:R:RPE|RPE]]|2.57|0.09| |[[:human_genes:S:SARS|SARS]]|2.81|0.39| |[[:human_genes:S:SUPV3L1|SUPV3L1]]|2.84|0.09| |[[:human_genes:S:SARS2|SARS2]]|2.97|0.09| |[[:human_genes:T:TRIAP1|TRIAP1]]|3.07|0.09| |[[:human_genes:G:GMPPB|GMPPB]]|3.59|0.09| ^Screen^Correlation^Plot^ |[[:results:exp68|Clomiphene 4.4μM R02 exp68]]|0.072|| |[[:results:exp90|WYE-354 6μM R02 exp90]]|0.07|| |[[:results:exp164|Q15 1 to 2μM on day4 R04 exp164]]|0.062|| |[[:results:exp344|Chlorpromazine 10μM R07 exp344]]|0.062|| |[[:results:exp442|Ibrutinib 10μM R08 exp442]]|0.06|| |[[:results:exp79|Q15 2.7μM R02 exp79]]|0.059|| |[[:results:exp507|Monensin 0.3μM R08 exp507]]|0.057|| |[[:results:exp26|Oligomycin-A 20μM R00 exp26]]|0.052|| |[[:results:exp530|Thioridazine 5μM R08 exp530]]|0.051|| |[[:results:exp434|Vemurafenib 6.6μM R08 exp434]]|0.051|| |[[:results:exp169|BH1 1μM R04 exp169]]|0.08|| |[[:results:exp461|BS-181 20μM R08 exp461]]|0.06|| |[[:results:exp539|42°C R08 exp539]]|0.056|| {{:chemogenomics:comparison_plots:exp469_vs_exp68.png?nolink |}} {{:chemogenomics:comparison_plots:exp469_vs_exp90.png?nolink |}} {{:chemogenomics:comparison_plots:exp164_vs_exp469.png?nolink |}} {{:chemogenomics:comparison_plots:exp344_vs_exp469.png?nolink |}} {{:chemogenomics:comparison_plots:exp442_vs_exp469.png?nolink |}} {{:chemogenomics:comparison_plots:exp469_vs_exp79.png?nolink |}} {{:chemogenomics:comparison_plots:exp469_vs_exp507.png?nolink |}} {{:chemogenomics:comparison_plots:exp26_vs_exp469.png?nolink |}} {{:chemogenomics:comparison_plots:exp469_vs_exp530.png?nolink |}} {{:chemogenomics:comparison_plots:exp434_vs_exp469.png?nolink |}} {{:chemogenomics:comparison_plots:exp169_vs_exp469.png?nolink |}} {{:chemogenomics:comparison_plots:exp461_vs_exp469.png?nolink |}} {{:chemogenomics:comparison_plots:exp469_vs_exp539.png?nolink |}} ^GO Term^Fold Change^Genes^ |COPI-coated vesicle membrane|131.50|SCYL1,COPZ1,COPB2| |COPI-coated vesicle|87.67|SCYL1,COPZ1,COPB2| |intra-Golgi vesicle-mediated transport|79.18|COG7,COPZ1,COG5,COPB2| |retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum|51.14|SCYL1,COG7,COPZ1,COPB2| |Golgi organization|27.68|GOLGA8H,COG7,YIPF5,ARL1,YIPF4,COG5| |Golgi vesicle transport|15.62|SCYL1,COG7,YIPF5,COPZ1,YIPF4,COG5,COPB2| |Golgi apparatus subcompartment|11.80|GOLGA8H,COG7,YIPF5,SGMS1,ARL1,YIPF4,COG5| |Golgi membrane|9.35|TMEM167B,COG7,SGMS1,ATP6V0A2,COPZ1,UNC50,ARL1,COG5,COPB2,PI4KB| No GO term hits below threshold. (FDR <0.05)