====== Temozolomide 200μM R04 exp189 ====== ==== Mechanism of Action ==== Alkylates purine bases, prodrug hydrolyzes to 3-methyl-(triazen-1-yl)imidazole-4-carboxamide (MTIC) * **Class / Subclass 1:** DNA Damage, Repair and Replication / Base Alkylation ==== Technical Notes ==== * **PubChem Name:** %%Temozolomide%% * **Synonyms:** NSC 362856; CCRG 81045; TMZ; NSC 362856;CCRG 81045;TMZ * **CAS #:** 85622-93-1 * **PubChem CID:** [[https://pubchem.ncbi.nlm.nih.gov/compound/5394|5394]] * **IUPAC:** %%3-methyl-4-oxoimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxamide%% * **INCHI Name:** InChI=1S/C6H6N6O2/c1-11-6(14)12-2-8-3(4(7)13)5(12)9-10-11/h2H,1H3,(H2,7,13) * **INCHI Key:** BPEGJWRSRHCHSN-UHFFFAOYSA-N * **Molecular Weight:** 194.15 * **Canonical SMILES:** CN1C(=O)N2C=NC(=C2N=N1)C(=O)N * **Isomeric SMILES:** N/A * **Molecular Formula:** C6H6N6O2 {{:chemogenomics:structures:chem-0122.svg?nolink}} * **Supplier Name:** Selleck Chemicals * **Catalog #:** S1237 * **Lot #:** N/A * **HRMS (ESI-TOF) m/z:** (M+H)+ Calcd for C6H6N6O2 195.0625; found 195.06203 * **Platform ID:** Temozolomide * **Min:** -5.2800; **Max:** 2.5972 {{:chemogenomics:dose_response:dr_245.png?nolink&500 |}} \\ \\ \\ \\ |< 300px 100px 200px >| ^ IC ^ Concentration (µM) ^ | IC10 |N/A | | IC20 |N/A | | IC30 |N/A | | IC40 |N/A | | IC50 |N/A | | IC60 |N/A | | IC70 |N/A | | IC80 |N/A | | IC90 |N/A | \\ ==== Screen Summary ==== * **Round**: 04 * **Dose**: 200µM * **Days of incubation**: 8 * **Doublings**: 4.9 * **Numbers of reads**: 18157051 ==== 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^ |14/19|[[https://files.tyerslab.com/files/public/chemogenomics/cranks/Temozolomide_200uM_Round-4_exp189.txt|Scores]]|||||| {{:chemogenomics:cranks_plots:exp189.png?nolink}} ^Gene^CRANKS Score^FDR^ |[[:human_genes:M:MDH1|MDH1]]|-4.26|<0.01| |[[:human_genes:N:NT5C2|NT5C2]]|-3.69|<0.01| |[[:human_genes:A:ADIPOR2|ADIPOR2]]|-3.30|<0.01| |[[:human_genes:M:MCM9|MCM9]]|-3.04|<0.01| |[[:human_genes:U:UXS1|UXS1]]|-3.03|<0.01| |[[:human_genes:M:MAD2L2|MAD2L2]]|-2.89|<0.01| |[[:human_genes:R:RNF25|RNF25]]|-2.89|<0.01| |[[:human_genes:P:PARP1|PARP1]]|-2.85|<0.01| |[[:human_genes:O:OTUB1|OTUB1]]|-2.83|0.01| |[[:human_genes:P:PPCS|PPCS]]|-2.68|0.03| |[[:human_genes:R:RCC2|RCC2]]|-2.65|0.01| |[[:human_genes:C:CHD1L|CHD1L]]|-2.59|0.02| |[[:human_genes:G:GOT1|GOT1]]|-2.56|0.02| |[[:human_genes:R:RHOA|RHOA]]|-2.44|0.04| |[[:human_genes:P:PARK2|PARK2]]|-2.37|0.05| |[[:human_genes:M:MAPK14|MAPK14]]|-2.37|0.05| |[[:human_genes:A:ACSL4|ACSL4]]|-2.31|0.13| |[[:human_genes:A:ARL1|ARL1]]|-2.30|0.07| |[[:human_genes:N:NSFL1C|NSFL1C]]|-2.27|0.08| |[[:human_genes:R:RPL36A-HNRNPH2|RPL36A-HNRNPH2]]|-2.25|0.62| |[[:human_genes:M:MYH13|MYH13]]|-2.24|0.24| |[[:human_genes:U:UBE2D3|UBE2D3]]|-2.19|0.12| |[[:human_genes:F:FCRLA|FCRLA]]|-2.16|0.13| |[[:human_genes:P:PRPS1|PRPS1]]|-2.16|0.21| |[[:human_genes:P:PNKP|PNKP]]|-2.16|0.36| |[[:human_genes:P:POLB|POLB]]|-2.14|0.14| |[[:human_genes:S:STIP1|STIP1]]|-2.14|0.21| |[[:human_genes:S:SNF8|SNF8]]|-2.13|0.21| |[[:human_genes:A:ATM|ATM]]|-2.11|0.16| |[[:human_genes:R:RSRC2|RSRC2]]|-2.11|0.40| |[[:human_genes:T:TP53BP2|TP53BP2]]|2.22|0.08| |[[:human_genes:S:SEPT4|SEPT4]]|2.24|0.08| |[[:human_genes:A:AGAP5|AGAP5]]|2.26|0.07| |[[:human_genes:I:INPP5F|INPP5F]]|2.30|0.06| |[[:human_genes:T:TSC1|TSC1]]|2.30|0.06| |[[:human_genes:N:NAA38|NAA38]]|2.31|0.22| |[[:human_genes:U:U2SURP|U2SURP]]|2.34|0.21| |[[:human_genes:D:DDX3X|DDX3X]]|2.34|0.05| |[[:human_genes:C:C2orf43|C2orf43]]|2.36|0.08| |[[:human_genes:I:IBA57|IBA57]]|2.36|0.05| |[[:human_genes:C:CNGB3|CNGB3]]|2.43|0.03| |[[:human_genes:P:PAICS|PAICS]]|2.48|0.35| |[[:human_genes:T:TSC2|TSC2]]|2.52|0.02| |[[:human_genes:U:USP16|USP16]]|2.56|0.02| |[[:human_genes:P:PNO1|PNO1]]|2.58|0.21| |[[:human_genes:N:NPRL2|NPRL2]]|2.58|0.02| |[[:human_genes:S:SLC25A1|SLC25A1]]|2.67|0.01| |[[:human_genes:C:CMAS|CMAS]]|2.79|<0.01| |[[:human_genes:M:MDH2|MDH2]]|2.86|0.01| |[[:human_genes:A:ABHD11|ABHD11]]|2.86|<0.01| |[[:human_genes:S:SFXN4|SFXN4]]|2.89|0.01| |[[:human_genes:I:IMPDH2|IMPDH2]]|2.92|<0.01| |[[:human_genes:N:NUDT5|NUDT5]]|2.93|<0.01| |[[:human_genes:A:ARID4B|ARID4B]]|2.96|<0.01| |[[:human_genes:N:NPRL3|NPRL3]]|2.97|0.01| |[[:human_genes:G:GOT2|GOT2]]|2.98|<0.01| |[[:human_genes:N:NANS|NANS]]|3.52|<0.01| |[[:human_genes:G:GCN1L1|GCN1L1]]|4.28|<0.01| |[[:human_genes:H:HPRT1|HPRT1]]|6.54|<0.01| |[[:human_genes:E:EIF2AK4|EIF2AK4]]|6.69|<0.01| ^Screen^Correlation^Plot^ |[[:results:exp216|Erlotinib 10μM R05 exp216]]|0.098|| {{:chemogenomics:comparison_plots:exp189_vs_exp216.png?nolink |}} ^GO Term^Fold Change^Genes^ |site of double-strand break|30.31|MAD2L2,PARP1,CHD1L,PNKP| |double-strand break repair|18.32|MCM9,MAD2L2,PARP1,PNKP,POLB,ATM| |DNA repair|11.75|MCM9,MAD2L2,PARP1,OTUB1,CHD1L,UBE2D3,PNKP,POLB,ATM| |DNA damage response|8.61|MCM9,MAD2L2,PARP1,OTUB1,CHD1L,MAPK14,UBE2D3,PNKP,POLB,ATM| |nucleobase-containing small molecule metabolic process|8.05|MDH1,NT5C2,UXS1,PARP1,PPCS,ACSL4,PRPS1| |DNA metabolic process|7.74|MCM9,MAD2L2,PARP1,OTUB1,CHD1L,UBE2D3,PNKP,POLB,ATM| ^GO Term^Fold Change^Genes^ |GATOR1 complex|552.47|NPRL3,NPRL2| |XMP metabolic process|184.16|IMPDH2,PAICS| |positive regulation of translation in response to stress|184.16|EIF2AK4,DDX3X| |GMP biosynthetic process|127.49|HPRT1,IMPDH2,PAICS| |purine ribonucleoside monophosphate biosynthetic process|92.08|HPRT1,IMPDH2,PAICS| |purine nucleoside monophosphate biosynthetic process|82.87|HPRT1,IMPDH2,PAICS| |GMP metabolic process|61.39|HPRT1,IMPDH2,PAICS| |negative regulation of TORC1 signaling|53.90|NPRL3,NPRL2,TSC2,TSC1| |ribonucleoside monophosphate biosynthetic process|48.75|HPRT1,IMPDH2,PAICS| |cellular response to amino acid starvation|46.04|EIF2AK4,GCN1,NPRL3,NPRL2| |response to amino acid starvation|43.33|EIF2AK4,GCN1,NPRL3,NPRL2| |negative regulation of TOR signaling|33.48|NPRL3,NPRL2,TSC2,TSC1| |regulation of TORC1 signaling|25.70|NPRL3,NPRL2,TSC2,TSC1| |cellular response to starvation|19.38|EIF2AK4,GCN1,NPRL3,NPRL2,TSC2,TSC1| |response to starvation|15.78|EIF2AK4,GCN1,NPRL3,NPRL2,TSC2,TSC1| |cellular response to nutrient levels|14.23|EIF2AK4,GCN1,NPRL3,NPRL2,TSC2,TSC1| |cellular response to extracellular stimulus|12.65|EIF2AK4,GCN1,NPRL3,NPRL2,TSC2,TSC1| |cellular response to external stimulus|10.14|EIF2AK4,GCN1,NPRL3,NPRL2,TSC2,TSC1| |nucleobase-containing small molecule metabolic process|7.24|HPRT1,NANS,NUDT5,IMPDH2,MDH2,SLC25A1,PAICS|