====== 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 |}}
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^ 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 |
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==== 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)