Methotrexate 0.01μM R08 exp501 [The Human Chemical-Genetic Interaction Map Project]

This page is read only. You can view the source, but not change it. Ask your administrator if you think this is wrong.
====== Methotrexate 0.01μM R08 exp501 ======
==== Mechanism of Action ====
Inhibits dihydrofolate reductase (DHFR)
  * **<color #00a2e8>Class / Subclass 1:</color>** Metabolism / Antimetabolite
  * **<color #00a2e8>Class / Subclass 2:</color>** DNA Damage, Repair and Replication / Replication Inhibitor



==== Technical Notes ====
<accordion collapsed='true'>
<panel title='Compound References' collapsed='true'>
    * **<color #00a2e8>PubChem Name:</color>** %%Methotrexate%%
    * **<color #00a2e8>Synonyms:</color>** Amethopterin; CL14377; WR19039; Amethopterin;CL14377;WR19039
    * **<color #00a2e8>CAS #:</color>** 59-05-2
    * **<color #00a2e8>PubChem CID:</color>** [[https://pubchem.ncbi.nlm.nih.gov/compound/126941|126941]]
    * **<color #00a2e8>IUPAC:</color>** %%(2S)-2-[[4-[(2,4-diaminopteridin-6-yl)methyl-methylamino]benzoyl]amino]pentanedioic acid%%
    * **<color #00a2e8>INCHI Name:</color>** InChI=1S/C20H22N8O5/c1-28(9-11-8-23-17-15(24-11)16(21)26-20(22)27-17)12-4-2-10(3-5-12)18(31)25-13(19(32)33)6-7-14(29)30/h2-5,8,13H,6-7,9H2,1H3,(H,25,31)(H,29,30)(H,32,33)(H4,21,22,23,26,27)/t13-/m0/s1
    * **<color #00a2e8>INCHI Key:</color>** FBOZXECLQNJBKD-ZDUSSCGKSA-N
    * **<color #00a2e8>Molecular Weight:</color>** 454.4
    * **<color #00a2e8>Canonical SMILES:</color>** CN(CC1=CN=C2C(=N1)C(=NC(=N2)N)N)C3=CC=C(C=C3)C(=O)NC(CCC(=O)O)C(=O)O
    * **<color #00a2e8>Isomeric SMILES:</color>** CN(CC1=CN=C2C(=N1)C(=NC(=N2)N)N)C3=CC=C(C=C3)C(=O)N[C@@H](CCC(=O)O)C(=O)O
    * **<color #00a2e8>Molecular Formula:</color>** C20H22N8O5
{{:chemogenomics:structures:chem-0306.svg?nolink}}
</panel>


<panel title='Compound Supplier' collapsed='true'>
    * **<color #00a2e8>Supplier Name:</color>** Toronto Research Chemicals
    * **<color #00a2e8>Catalog #:</color>** M260675
    * **<color #00a2e8>Lot #:</color>** 2-ZPK-113-1
</panel>


<panel title='Compound Characterization' collapsed='true'>
    * **<color #00a2e8>HRMS (ESI-TOF) m/z:</color>** (M+H)+ Calcd for C20H22N8O5 455.17859; found 455.17795
</panel>


<panel title='Dose Response Curve' collapsed='true'>
    * **<color #00a2e8>Platform ID:</color>** Methotrexate
    * **<color #00a2e8>Min:</color>** -8.2495; **<color #00a2e8>Max:</color>** 94.1747
{{:chemogenomics:dose_response:dr_554.png?nolink&500 |}}
\\ 
\\ 
\\ 
\\ 
|< 300px 100px 200px >|
^ IC   ^ Concentration (µM) ^
| IC10  |0.0074    |
| IC20  |0.0091    |
| IC30  |0.0105    |
| IC40  |0.0117    |
| IC50  |0.0130    |
| IC60  |0.0144    |
| IC70  |0.0161    |
| IC80  |0.0185    |
| IC90  |0.0227    |
\\ 
</panel>
</accordion>
==== Screen Summary ====
    * **<color #00a2e8>Round</color>**: 08
    * **<color #00a2e8>Dose</color>**: 10nM
    * **<color #00a2e8>Days of incubation</color>**: 8
    * **<color #00a2e8>Doublings</color>**: 6.2
    * **<color #00a2e8>Numbers of reads</color>**: 17006804


==== 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^
|15/12|<color #e85500>[[https://files.tyerslab.com/files/public/chemogenomics/cranks/Methotrexate_0.01uM_Round-8_exp501.txt|Scores]]</color>|<button type="primary" size="sm" modal="ScorePlot">View</button>|<button type="primary" size="sm" modal="modal_hits">View</button>|<button type="primary" size="sm" modal="modal_screen_similarity">View</button>|<button type="primary" size="sm" modal="modal_go_sensitive">View</button>|<button type="primary" size="sm" modal="modal_go_resistant">View</button>|
<modal id='ScorePlot' size='lg' title='Methotrexate 0.01μM R08 exp501'>
{{:chemogenomics:cranks_plots:exp501.png?nolink}}
</modal>


<modal id="modal_hits" size="sm" title="Top 30 S/R Genes">
^Gene^CRANKS Score^FDR^
|[[:human_genes:S:SLC25A32|SLC25A32]]|-3.52|<0.01|
|[[:human_genes:M:MTR|MTR]]|-3.21|<0.01|
|[[:human_genes:F:FAM58A|FAM58A]]|-3.08|<0.01|
|[[:human_genes:M:MMACHC|MMACHC]]|-2.83|0.01|
|[[:human_genes:M:MTHFD2|MTHFD2]]|-2.77|0.01|
|[[:human_genes:M:MSI2|MSI2]]|-2.74|0.01|
|[[:human_genes:P:POTEE|POTEE]]|-2.68|0.09|
|[[:human_genes:G:G3BP1|G3BP1]]|-2.62|0.03|
|[[:human_genes:C:CDK12|CDK12]]|-2.55|0.05|
|[[:human_genes:M:MTRR|MTRR]]|-2.49|0.04|
|[[:human_genes:U:USP10|USP10]]|-2.48|0.04|
|[[:human_genes:M:MTHFD1L|MTHFD1L]]|-2.47|0.04|
|[[:human_genes:S:SFXN1|SFXN1]]|-2.44|0.04|
|[[:human_genes:P:PGF|PGF]]|-2.44|0.06|
|[[:human_genes:N:NR2C2|NR2C2]]|-2.44|0.04|
|[[:human_genes:U:UFC1|UFC1]]|-2.41|0.05|
|[[:human_genes:E:EPN1|EPN1]]|-2.41|0.05|
|[[:human_genes:N:NADK|NADK]]|-2.36|0.14|
|[[:human_genes:D:DENR|DENR]]|-2.34|0.06|
|[[:human_genes:M:MCTS1|MCTS1]]|-2.33|0.06|
|[[:human_genes:I:INO80E|INO80E]]|-2.32|0.10|
|[[:human_genes:Q:QRICH1|QRICH1]]|-2.32|0.06|
|[[:human_genes:T:TMEM185B|TMEM185B]]|-2.32|0.06|
|[[:human_genes:L:LARP4B|LARP4B]]|-2.31|0.06|
|[[:human_genes:D:DAZAP1|DAZAP1]]|-2.28|0.06|
|[[:human_genes:S:SHMT2|SHMT2]]|-2.28|0.16|
|[[:human_genes:P:PPIL4|PPIL4]]|-2.21|0.20|
|[[:human_genes:D:DDX39B|DDX39B]]|-2.20|0.14|
|[[:human_genes:A:ATIC|ATIC]]|-2.20|0.09|
|[[:human_genes:D:DHX36|DHX36]]|-2.18|0.14|
|[[:human_genes:S:SLU7|SLU7]]|2.13|0.36|
|[[:human_genes:E:EZH2|EZH2]]|2.13|0.18|
|[[:human_genes:M:MYH2|MYH2]]|2.14|0.23|
|[[:human_genes:F:FAM231B|FAM231B]]|2.19|0.23|
|[[:human_genes:E:E2F1|E2F1]]|2.21|0.26|
|[[:human_genes:C:CPVL|CPVL]]|2.23|0.20|
|[[:human_genes:T:TSC22D2|TSC22D2]]|2.24|0.12|
|[[:human_genes:S:STIP1|STIP1]]|2.25|0.24|
|[[:human_genes:C:CDK2|CDK2]]|2.26|0.11|
|[[:human_genes:R:RNF214|RNF214]]|2.27|0.18|
|[[:human_genes:S:SLC19A1|SLC19A1]]|2.27|0.23|
|[[:human_genes:C:C9orf41|C9orf41]]|2.29|0.23|
|[[:human_genes:U:UNK|UNK]]|2.30|0.16|
|[[:human_genes:H:HIST1H2AL|HIST1H2AL]]|2.30|0.16|
|[[:human_genes:F:FRMPD4|FRMPD4]]|2.31|0.09|
|[[:human_genes:T:TBCC|TBCC]]|2.41|0.44|
|[[:human_genes:R:RBM6|RBM6]]|2.43|0.05|
|[[:human_genes:E:E2F7|E2F7]]|2.48|0.04|
|[[:human_genes:R:RFC1|RFC1]]|2.52|0.23|
|[[:human_genes:T:TMEM219|TMEM219]]|2.52|0.03|
|[[:human_genes:P:PTP4A1|PTP4A1]]|2.56|0.03|
|[[:human_genes:P:POLR2C|POLR2C]]|2.76|0.28|
|[[:human_genes:P:PARP2|PARP2]]|2.83|0.02|
|[[:human_genes:C:CCNT1|CCNT1]]|2.90|<0.01|
|[[:human_genes:M:MBNL1|MBNL1]]|2.93|<0.01|
|[[:human_genes:Z:ZBTB7A|ZBTB7A]]|2.98|<0.01|
|[[:human_genes:Y:YLPM1|YLPM1]]|3.45|<0.01|
|[[:human_genes:E:E2F2|E2F2]]|3.47|<0.01|
|[[:human_genes:O:ODC1|ODC1]]|3.52|<0.01|
|[[:human_genes:N:NAA60|NAA60]]|5.45|<0.01|
</modal>


<modal id="modal_screen_similarity" size="lg" title="Correlated Screens">
^Screen^Correlation^Plot^
|[[:results:exp335|Aminopterin 0.005μM R07 exp335]]|0.081|<button type="primary" size="small" modal="1">View</button>|
</modal>


<modal id="1" size="lg" title="Aminopterin 0.005μM R07 exp335  vs  Methotrexate 0.01μM R08 exp501">
{{:chemogenomics:comparison_plots:exp335_vs_exp501.png?nolink |}}
</modal>



<modal id="modal_go_sensitive" size="lg" title="Top 30 sensitive GO terms">
^GO Term^Fold Change^Genes^
|tetrahydrofolate interconversion|253.61|MTHFD2,MTHFD1L,SHMT2|
|oxidoreductase activity, acting on metal ions, NAD or NADP as acceptor|236.70|MMACHC,MTRR|
|tetrahydrofolate metabolic process|227.60|MTR,MTHFD2,MTHFD1L,SHMT2,ATIC|
|folic acid-containing compound metabolic process|147.94|MTR,MTHFD2,MTRR,MTHFD1L,SHMT2,ATIC|
|pteridine-containing compound metabolic process|138.07|SLC25A32,MTR,MTHFD2,MTRR,MTHFD1L,SHMT2,ATIC|
|folic acid metabolic process|126.80|SLC25A32,MTHFD2,SHMT2|
|one-carbon metabolic process|65.75|MTHFD2,MTHFD1L,SFXN1,SHMT2|
|water-soluble vitamin metabolic process|61.22|SLC25A32,MTR,MMACHC,MTHFD2,MTRR,SHMT2|
|dicarboxylic acid metabolic process|40.81|SLC25A32,MTHFD2,MTRR,MTHFD1L,SHMT2,ATIC|
|cellular modified amino acid metabolic process|36.66|SLC25A32,MTR,MTHFD2,MTRR,MTHFD1L,SHMT2,ATIC|
|vitamin metabolic process|36.60|SLC25A32,MTR,MMACHC,MTHFD2,MTRR,SHMT2|
|mRNA binding|11.38|MSI2,G3BP1,DENR,LARP4B,DAZAP1,SHMT2|
</modal>
<modal id="modal_go_resistant" size="lg" title="Top 30 resistant GO terms">
^GO Term^Fold Change^Genes^
|Rb-E2F complex|368.20|E2F2,E2F1|
|regulation of transcription involved in G1/S transition of mitotic cell cycle|78.90|E2F2,E2F7,E2F1|
|G1/S transition of mitotic cell cycle|32.49|E2F2,E2F7,CDK2,E2F1,EZH2|
|cell cycle G1/S phase transition|32.11|E2F2,E2F7,CDK2,E2F1,EZH2|
|mitotic cell cycle phase transition|17.05|E2F2,E2F7,CDK2,E2F1,EZH2|
|cell cycle phase transition|15.87|E2F2,E2F7,CDK2,E2F1,EZH2|
</modal>