====== Campthothecin 0.001μM R06 exp270 ====== ==== Mechanism of Action ==== Inhibits topoisomerase I, stabilizes TopoI-DNA complex, causes DNA strand breaks * **Class / Subclass 1:** DNA Damage, Repair and Replication / Clastogen ==== Technical Notes ==== * **PubChem Name:** %%Camptothecin%% * **Synonyms:** Camptothecin; (S)-(+)-Camptothecin; CPT * **CAS #:** 7689-03-4 * **PubChem CID:** [[https://pubchem.ncbi.nlm.nih.gov/compound/24360|24360]] * **IUPAC:** %%(19S)-19-ethyl-19-hydroxy-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4,6,8,10,15(20)-heptaene-14,18-dione%% * **INCHI Name:** InChI=1S/C20H16N2O4/c1-2-20(25)14-8-16-17-12(7-11-5-3-4-6-15(11)21-17)9-22(16)18(23)13(14)10-26-19(20)24/h3-8,25H,2,9-10H2,1H3/t20-/m0/s1 * **INCHI Key:** VSJKWCGYPAHWDS-FQEVSTJZSA-N * **Molecular Weight:** 348.4 * **Canonical SMILES:** CCC1(C2=C(COC1=O)C(=O)N3CC4=CC5=CC=CC=C5N=C4C3=C2)O * **Isomeric SMILES:** CC[C@@]1(C2=C(COC1=O)C(=O)N3CC4=CC5=CC=CC=C5N=C4C3=C2)O * **Molecular Formula:** C20H16N2O4 {{:chemogenomics:structures:chem-0162.svg?nolink}} * **Supplier Name:** Sigma-Aldrich * **Catalog #:** C9911 * **Lot #:** N/A * **HRMS (ESI-TOF) m/z:** (M+H)+ Calcd for C20H16N2O4 349.11828; found 349.11567 * **Platform ID:** Camptothecin * **Min:** 25.8061; **Max:** 99.6985 {{:chemogenomics:dose_response:dr_315.png?nolink&500 |}} \\ \\ \\ \\ |< 300px 100px 200px >| ^ IC ^ Concentration (µM) ^ | IC10 |N/A | | IC20 |N/A | | IC30 |0.0006 | | IC40 |N/A | | IC50 |0.0010 | | IC60 |N/A | | IC70 |N/A | | IC80 |N/A | | IC90 |N/A | \\ ==== Screen Summary ==== * **Round**: 06 * **Dose**: 1nM * **Days of incubation**: 8 * **Doublings**: 5.8 * **Numbers of reads**: 8689434 ==== 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^ |7/0|[[https://files.tyerslab.com/files/public/chemogenomics/cranks/Campthothecin_0.001uM_Round-6_exp270.txt|Scores]]|||||| {{:chemogenomics:cranks_plots:exp270.png?nolink}} ^Gene^CRANKS Score^FDR^ |[[:human_genes:M:MCM9|MCM9]]|-3.84|<0.01| |[[:human_genes:M:MCM8|MCM8]]|-3.30|<0.01| |[[:human_genes:S:STRA13|STRA13]]|-3.29|<0.01| |[[:human_genes:A:ATM|ATM]]|-3.09|<0.01| |[[:human_genes:S:SWI5|SWI5]]|-2.72|0.04| |[[:human_genes:S:SWSAP1|SWSAP1]]|-2.70|0.02| |[[:human_genes:N:NBN|NBN]]|-2.65|0.03| |[[:human_genes:A:ANKRD32|ANKRD32]]|-2.48|0.18| |[[:human_genes:P:PARP1|PARP1]]|-2.44|0.07| |[[:human_genes:K:KPNA4|KPNA4]]|-2.39|0.08| |[[:human_genes:U:UIMC1|UIMC1]]|-2.35|0.27| |[[:human_genes:A:APITD1-CORT|APITD1-CORT]]|-2.34|0.10| |[[:human_genes:R:RNF8|RNF8]]|-2.31|0.10| |[[:human_genes:C:CDIPT|CDIPT]]|-2.28|0.62| |[[:human_genes:R:RNASEH2A|RNASEH2A]]|-2.26|0.30| |[[:human_genes:M:MDM2|MDM2]]|-2.25|0.44| |[[:human_genes:S:SAFB|SAFB]]|-2.22|0.17| |[[:human_genes:P:PPP1R15A|PPP1R15A]]|-2.19|0.27| |[[:human_genes:A:ANAPC15|ANAPC15]]|-2.16|0.28| |[[:human_genes:C:C19orf40|C19orf40]]|-2.14|0.22| |[[:human_genes:T:TCF4|TCF4]]|-2.08|0.27| |[[:human_genes:E:ERCC2|ERCC2]]|-2.08|0.49| |[[:human_genes:K:KRT222|KRT222]]|-2.07|0.27| |[[:human_genes:M:METTL14|METTL14]]|-2.06|0.44| |[[:human_genes:C:CHGB|CHGB]]|-2.05|0.33| |[[:human_genes:U:UBE2J1|UBE2J1]]|-2.05|0.28| |[[:human_genes:C:C1orf112|C1orf112]]|-2.04|0.33| |[[:human_genes:E:EIF1|EIF1]]|-2.03|0.44| |[[:human_genes:S:SPIDR|SPIDR]]|-2.02|0.29| |[[:human_genes:D:DNAJB9|DNAJB9]]|-1.99|0.30| |[[:human_genes:N:NOL12|NOL12]]|1.95|0.65| |[[:human_genes:N:NPIPA5|NPIPA5]]|1.96|0.70| |[[:human_genes:N:NCSTN|NCSTN]]|1.96|0.57| |[[:human_genes:T:TMEM134|TMEM134]]|1.97|0.57| |[[:human_genes:S:SMG5|SMG5]]|1.98|0.75| |[[:human_genes:S:SRPK3|SRPK3]]|1.99|0.57| |[[:human_genes:M:MED14|MED14]]|1.99|0.57| |[[:human_genes:P:PPP1R8|PPP1R8]]|2.00|0.57| |[[:human_genes:C:COPB1|COPB1]]|2.01|0.70| |[[:human_genes:D:DNM2|DNM2]]|2.03|0.78| |[[:human_genes:C:CPEB2|CPEB2]]|2.04|0.70| |[[:human_genes:P:POLDIP2|POLDIP2]]|2.05|0.57| |[[:human_genes:N:NDUFB7|NDUFB7]]|2.06|0.58| |[[:human_genes:L:LYG2|LYG2]]|2.07|0.57| |[[:human_genes:R:RPL11|RPL11]]|2.09|0.78| |[[:human_genes:M:MT1X|MT1X]]|2.09|0.57| |[[:human_genes:C:C19orf59|C19orf59]]|2.11|0.57| |[[:human_genes:H:HMHA1|HMHA1]]|2.11|0.57| |[[:human_genes:T:TOP1MT|TOP1MT]]|2.13|0.57| |[[:human_genes:E:EIF4A3|EIF4A3]]|2.15|0.64| |[[:human_genes:R:RPS5|RPS5]]|2.18|0.57| |[[:human_genes:K:KDR|KDR]]|2.28|0.57| |[[:human_genes:P:PSMC3|PSMC3]]|2.28|0.65| |[[:human_genes:S:SLC2A1|SLC2A1]]|2.28|0.57| |[[:human_genes:S:SLC10A7|SLC10A7]]|2.31|0.30| |[[:human_genes:T:TCN2|TCN2]]|2.35|0.42| |[[:human_genes:C:CERKL|CERKL]]|2.39|0.26| |[[:human_genes:P:PIK3CD|PIK3CD]]|2.43|0.26| |[[:human_genes:F:FAM72C|FAM72C]]|2.50|0.70| |[[:human_genes:S:SOWAHA|SOWAHA]]|2.56|0.26| ^Screen^Correlation^Plot^ |[[:results:exp520|Rucaparib 6.5μM R08 exp520]]|0.081|| |[[:results:exp512|Olaparib 4μM R08 exp512]]|0.056|| |[[:results:exp299|Talazoparib 0.006μM R06 exp299]]|0.052|| {{:chemogenomics:comparison_plots:exp270_vs_exp520.png?nolink |}} {{:chemogenomics:comparison_plots:exp270_vs_exp512.png?nolink |}} {{:chemogenomics:comparison_plots:exp270_vs_exp299.png?nolink |}} ^GO Term^Fold Change^Genes^ |interstrand cross-link repair|74.99|MCM9,MCM8,CENPX,RNF8| |DNA-templated DNA replication maintenance of fidelity|60.13|MCM9,MCM8,CENPX,NBN,PARP1| |recombinational repair|42.85|MCM9,MCM8,ATM,SWI5,SWSAP1,NBN,SLF1,SPIDR| |site of double-strand break|39.34|NBN,SLF1,PARP1,UIMC1,RNF8| |double-strand break repair via homologous recombination|38.46|MCM9,MCM8,ATM,SWI5,NBN,SLF1,SPIDR| |double-strand break repair|34.88|MCM9,MCM8,ATM,SWI5,SWSAP1,NBN,SLF1,PARP1,UIMC1,RNF8,SPIDR| |response to ionizing radiation|33.55|ATM,SWI5,PARP1,UIMC1,RNF8,MDM2,SPIDR| |site of DNA damage|29.51|NBN,SLF1,PARP1,UIMC1,RNF8| |DNA recombination|28.33|MCM9,MCM8,CENPX,ATM,SWI5,SWSAP1,NBN,SLF1,RNF8,SPIDR| |positive regulation of DNA repair|26.12|SLF1,PARP1,UIMC1,RNF8,SPIDR| |DNA-templated DNA replication|24.33|MCM9,MCM8,CENPX,NBN,PARP1| |signal transduction in response to DNA damage|22.93|ATM,NBN,UIMC1,RNF8,MDM2| |DNA replication|19.71|MCM9,MCM8,CENPX,NBN,PARP1,RNASEH2A| |DNA repair|18.95|MCM9,MCM8,CENPX,ATM,SWI5,SWSAP1,NBN,SLF1,PARP1,UIMC1,RNF8,RNASEH2A,ERCC2,SPIDR| |positive regulation of DNA metabolic process|17.77|ATM,NBN,SLF1,PARP1,UIMC1,RNF8,ERCC2,SPIDR| |DNA damage response|14.26|MCM9,MCM8,CENPX,ATM,SWI5,SWSAP1,NBN,SLF1,PARP1,UIMC1,RNF8,RNASEH2A,MDM2,PPP1R15A,ERCC2,SPIDR| |DNA metabolic process|12.46|MCM9,MCM8,CENPX,ATM,SWI5,SWSAP1,NBN,SLF1,PARP1,UIMC1,RNF8,RNASEH2A,ERCC2,SPIDR| |response to radiation|12.44|ATM,SWI5,PARP1,UIMC1,RNF8,MDM2,ERCC2,SPIDR| |regulation of DNA metabolic process|10.06|ATM,NBN,SLF1,PARP1,UIMC1,RNF8,ERCC2,SPIDR| No GO term hits below threshold. (FDR <0.05)