====== MLN-4924 0.2μM R00 exp21 ======
==== Mechanism of Action ====
Inhibits NEDD8-activating enzyme (NAE), prevents activity of cullin-RING ligase (CRL) E3 enzymes
* **Class / Subclass 1:** Proteostasis / NEDDylation Inhibitor
==== Technical Notes ====
* **PubChem Name:** %%Pevonedistat%%
* **Synonyms:** MLN4924
* **CAS #:** 905579-51-3
* **PubChem CID:** [[https://pubchem.ncbi.nlm.nih.gov/compound/16720766|16720766]]
* **IUPAC:** %%[(1S,2S,4R)-4-[4-[[(1S)-2,3-dihydro-1H-inden-1-yl]amino]pyrrolo[2,3-d]pyrimidin-7-yl]-2-hydroxycyclopentyl]methyl sulfamate%%
* **INCHI Name:** InChI=1S/C21H25N5O4S/c22-31(28,29)30-11-14-9-15(10-19(14)27)26-8-7-17-20(23-12-24-21(17)26)25-18-6-5-13-3-1-2-4-16(13)18/h1-4,7-8,12,14-15,18-19,27H,5-6,9-11H2,(H2,22,28,29)(H,23,24,25)/t14-,15+,18-,19-/m0/s1
* **INCHI Key:** MPUQHZXIXSTTDU-QXGSTGNESA-N
* **Molecular Weight:** 443.5
* **Canonical SMILES:** C1CC2=CC=CC=C2C1NC3=C4C=CN(C4=NC=N3)C5CC(C(C5)O)COS(=O)(=O)N
* **Isomeric SMILES:** C1CC2=CC=CC=C2[C@H]1NC3=C4C=CN(C4=NC=N3)[C@@H]5C[C@H]([C@H](C5)O)COS(=O)(=O)N
* **Molecular Formula:** C21H25N5O4S
{{:chemogenomics:structures:chem-0012.svg?nolink}}
* **Supplier Name:** N/A
* **Catalog #:** N/A
* **Lot #:** N/A
Characterization data not available.
* **Platform ID:** MLN-4924
* **Min:** 0.2392; **Max:** 97.5121
{{:chemogenomics:dose_response:dr_269.png?nolink&500 |}}
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^ IC ^ Concentration (µM) ^
| IC10 |N/A |
| IC20 |0.0970 |
| IC30 |0.1416 |
| IC40 |0.1931 |
| IC50 |0.2566 |
| IC60 |N/A |
| IC70 |N/A |
| IC80 |N/A |
| IC90 |N/A |
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==== Screen Summary ====
* **Round**: 00
* **Dose**: 200nM
* **Days of incubation**: 8
* **Doublings**: 2.3
* **Numbers of reads**: 11224381
==== 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^
|21/115|[[https://files.tyerslab.com/files/public/chemogenomics/cranks/MLN-4924_0.2uM_Round-0_exp21.txt|Scores]]||||||
{{:chemogenomics:cranks_plots:exp21.png?nolink}}
^Gene^CRANKS Score^FDR^
|[[:human_genes:R:RAB5C|RAB5C]]|-3.66|<0.01|
|[[:human_genes:C:CNOT8|CNOT8]]|-3.43|<0.01|
|[[:human_genes:A:ABCG2|ABCG2]]|-3.11|<0.01|
|[[:human_genes:C:CNOT2|CNOT2]]|-3.05|<0.01|
|[[:human_genes:S:SZT2|SZT2]]|-2.99|<0.01|
|[[:human_genes:C:CUL4A|CUL4A]]|-2.97|<0.01|
|[[:human_genes:P:PDS5B|PDS5B]]|-2.96|<0.01|
|[[:human_genes:N:NONO|NONO]]|-2.94|<0.01|
|[[:human_genes:C:C12orf66|C12orf66]]|-2.93|<0.01|
|[[:human_genes:D:DEPDC5|DEPDC5]]|-2.89|<0.01|
|[[:human_genes:H:HDAC3|HDAC3]]|-2.70|0.01|
|[[:human_genes:T:TMEM127|TMEM127]]|-2.68|0.01|
|[[:human_genes:U:UBE2G1|UBE2G1]]|-2.64|0.01|
|[[:human_genes:U:UBE2C|UBE2C]]|-2.61|0.02|
|[[:human_genes:T:TUBB|TUBB]]|-2.55|0.07|
|[[:human_genes:F:FZR1|FZR1]]|-2.45|0.03|
|[[:human_genes:P:PBRM1|PBRM1]]|-2.44|0.03|
|[[:human_genes:G:GLMN|GLMN]]|-2.43|0.04|
|[[:human_genes:B:BRD7|BRD7]]|-2.39|0.04|
|[[:human_genes:S:SIVA1|SIVA1]]|-2.37|0.05|
|[[:human_genes:M:MSL1|MSL1]]|-2.35|0.05|
|[[:human_genes:N:NSMCE1|NSMCE1]]|-2.35|0.05|
|[[:human_genes:L:LRP10|LRP10]]|-2.31|0.14|
|[[:human_genes:C:CSK|CSK]]|-2.29|0.06|
|[[:human_genes:K:KPTN|KPTN]]|-2.28|0.06|
|[[:human_genes:O:OTUB1|OTUB1]]|-2.27|0.10|
|[[:human_genes:Z:ZCRB1|ZCRB1]]|-2.22|0.08|
|[[:human_genes:V:VPS51|VPS51]]|-2.21|0.12|
|[[:human_genes:P:PRSS3|PRSS3]]|-2.19|0.12|
|[[:human_genes:P:PRR14L|PRR14L]]|-2.18|0.09|
|[[:human_genes:S:STRAP|STRAP]]|3.35|<0.01|
|[[:human_genes:M:MAPKAP1|MAPKAP1]]|3.44|<0.01|
|[[:human_genes:Z:ZNF598|ZNF598]]|3.49|<0.01|
|[[:human_genes:D:DENND4A|DENND4A]]|3.51|<0.01|
|[[:human_genes:C:CTU2|CTU2]]|3.52|<0.01|
|[[:human_genes:S:SUV420H1|SUV420H1]]|3.53|<0.01|
|[[:human_genes:M:METAP1|METAP1]]|3.53|<0.01|
|[[:human_genes:R:RPTOR|RPTOR]]|3.53|<0.01|
|[[:human_genes:A:ASUN|ASUN]]|3.55|<0.01|
|[[:human_genes:M:MOCS3|MOCS3]]|3.58|<0.01|
|[[:human_genes:A:ATP2B1|ATP2B1]]|3.59|<0.01|
|[[:human_genes:W:WDR24|WDR24]]|3.63|<0.01|
|[[:human_genes:R:RCOR1|RCOR1]]|3.65|<0.01|
|[[:human_genes:T:TAF3|TAF3]]|3.77|<0.01|
|[[:human_genes:E:EED|EED]]|3.83|<0.01|
|[[:human_genes:C:COPS8|COPS8]]|3.87|<0.01|
|[[:human_genes:S:SUZ12|SUZ12]]|3.95|<0.01|
|[[:human_genes:M:MBNL1|MBNL1]]|4.48|<0.01|
|[[:human_genes:U:UBE2G2|UBE2G2]]|4.60|<0.01|
|[[:human_genes:E:EIF4G1|EIF4G1]]|4.65|<0.01|
|[[:human_genes:S:SLC7A1|SLC7A1]]|4.88|<0.01|
|[[:human_genes:A:AZIN1|AZIN1]]|5.04|<0.01|
|[[:human_genes:M:MLST8|MLST8]]|5.23|<0.01|
|[[:human_genes:S:SLC12A2|SLC12A2]]|5.43|<0.01|
|[[:human_genes:E:EIF4A1|EIF4A1]]|5.45|<0.01|
|[[:human_genes:C:COPS4|COPS4]]|5.65|<0.01|
|[[:human_genes:C:COPS2|COPS2]]|6.08|<0.01|
|[[:human_genes:E:EZH2|EZH2]]|6.72|<0.01|
|[[:human_genes:C:COPS7B|COPS7B]]|7.28|<0.01|
|[[:human_genes:B:BEND3|BEND3]]|8.48|<0.01|
^Screen^Correlation^Plot^
|[[:results:exp102|Nifuroxazide 5μM R03 exp102]]|0.105||
|[[:results:exp444|THZ531 0.225μM R08 exp444]]|0.099||
|[[:results:exp35|TRAIL 5ng/ml R00 exp35]]|0.087||
|[[:results:exp535|Trimetrexate 0.03μM R08 exp535]]|0.085||
|[[:results:exp526|Sulforaphane 9μM R08 exp526 no dilution day6]]|0.083||
|[[:results:exp134|MS023 2μM R03 exp134]]|0.079||
|[[:results:exp135|MS023 7μM R03 exp135]]|0.077||
|[[:results:exp36|TRAIL 50ng/ml R00 exp36]]|0.073||
|[[:results:exp412|THZ531 0.11 to 0.125 to 0.35μM on day4 then day6 R07 exp412]]|0.071||
|[[:results:exp413|THZ531 0.11 to 0.175μM on day4 R07 exp413]]|0.068||
|[[:results:exp525|Sulforaphane 9μM R08 exp525]]|0.066||
|[[:results:exp512|Olaparib 4μM R08 exp512]]|0.062||
|[[:results:exp517|Quercetin 20μM R08 exp517]]|0.053||
|[[:results:exp515|PU-H71 1μM R08 exp515]]|0.052||
|[[:results:exp499|LY2090314 0.003μM R08 exp499]]|0.102||
|[[:results:exp505|ML-792 0.2μM R08 exp505]]|0.096||
|[[:results:exp500|LY2090314 0.003μM R08 exp500 no dilution day6]]|0.09||
|[[:results:exp456|Benzoate 20000μM R08 exp456]]|0.082||
|[[:results:exp468|CB-5083 0.4μM R08 exp468]]|0.075||
|[[:results:exp489|Hippuristanol 0.12μM R08 exp489 no dilution day6]]|0.074||
|[[:results:exp488|Hippuristanol 0.12μM R08 exp488]]|0.074||
|[[:results:exp447|Amiloride 100μM R08 exp447]]|0.07||
|[[:results:exp259|6-Thio-2-deoxyguanosine 2μM R06 exp259]]|0.069||
|[[:results:exp211|AICAR 240μM R05 exp211]]|0.066||
|[[:results:exp264|Arsenate 40μM R06 exp264]]|0.066||
|[[:results:exp234|Ethanol 0.01 R05 exp234]]|0.065||
|[[:results:exp3|Actinomycin-D 0.001μM R00 exp3]]|0.06||
|[[:results:exp199|Etoposide 0.3μM R05 exp199]]|0.055||
|[[:results:exp485|GSK626616 14μM R08 exp485]]|0.055||
|[[:results:exp450|Artemisinin 50μM R08 exp450]]|0.054||
|[[:results:exp116|AICAR 240μM R03 exp116]]|0.054||
|[[:results:exp2|5-Fluorouracil 20μM R00 exp2]]|0.053||
|[[:results:exp214|2-Deoxy-D-glucose 800μM R05 exp214]]|0.053||
|[[:results:exp440|Aphidicolin 0.4μM R08 exp440]]|0.052||
{{:chemogenomics:comparison_plots:exp102_vs_exp21.png?nolink |}}
{{:chemogenomics:comparison_plots:exp21_vs_exp444.png?nolink |}}
{{:chemogenomics:comparison_plots:exp21_vs_exp35.png?nolink |}}
{{:chemogenomics:comparison_plots:exp21_vs_exp535.png?nolink |}}
{{:chemogenomics:comparison_plots:exp21_vs_exp526.png?nolink |}}
{{:chemogenomics:comparison_plots:exp134_vs_exp21.png?nolink |}}
{{:chemogenomics:comparison_plots:exp135_vs_exp21.png?nolink |}}
{{:chemogenomics:comparison_plots:exp21_vs_exp36.png?nolink |}}
{{:chemogenomics:comparison_plots:exp21_vs_exp412.png?nolink |}}
{{:chemogenomics:comparison_plots:exp21_vs_exp413.png?nolink |}}
{{:chemogenomics:comparison_plots:exp21_vs_exp525.png?nolink |}}
{{:chemogenomics:comparison_plots:exp21_vs_exp512.png?nolink |}}
{{:chemogenomics:comparison_plots:exp21_vs_exp517.png?nolink |}}
{{:chemogenomics:comparison_plots:exp21_vs_exp515.png?nolink |}}
{{:chemogenomics:comparison_plots:exp21_vs_exp499.png?nolink |}}
{{:chemogenomics:comparison_plots:exp21_vs_exp505.png?nolink |}}
{{:chemogenomics:comparison_plots:exp21_vs_exp500.png?nolink |}}
{{:chemogenomics:comparison_plots:exp21_vs_exp456.png?nolink |}}
{{:chemogenomics:comparison_plots:exp21_vs_exp468.png?nolink |}}
{{:chemogenomics:comparison_plots:exp21_vs_exp489.png?nolink |}}
{{:chemogenomics:comparison_plots:exp21_vs_exp488.png?nolink |}}
{{:chemogenomics:comparison_plots:exp21_vs_exp447.png?nolink |}}
{{:chemogenomics:comparison_plots:exp21_vs_exp259.png?nolink |}}
{{:chemogenomics:comparison_plots:exp21_vs_exp211.png?nolink |}}
{{:chemogenomics:comparison_plots:exp21_vs_exp264.png?nolink |}}
{{:chemogenomics:comparison_plots:exp21_vs_exp234.png?nolink |}}
{{:chemogenomics:comparison_plots:exp21_vs_exp3.png?nolink |}}
{{:chemogenomics:comparison_plots:exp199_vs_exp21.png?nolink |}}
{{:chemogenomics:comparison_plots:exp21_vs_exp485.png?nolink |}}
{{:chemogenomics:comparison_plots:exp21_vs_exp450.png?nolink |}}
{{:chemogenomics:comparison_plots:exp116_vs_exp21.png?nolink |}}
{{:chemogenomics:comparison_plots:exp2_vs_exp21.png?nolink |}}
{{:chemogenomics:comparison_plots:exp21_vs_exp214.png?nolink |}}
{{:chemogenomics:comparison_plots:exp21_vs_exp440.png?nolink |}}
^GO Term^Fold Change^Genes^
|ubiquitin-protein transferase regulator activity|74.02|FZR1,GLMN,OTUB1|
|negative regulation of TOR signaling|35.89|SZT2,DEPDC5,TMEM127,KPTN|
|regulation of TORC1 signaling|27.54|SZT2,DEPDC5,KPTN,OTUB1|
|regulation of TOR signaling|21.93|SZT2,DEPDC5,HDAC3,TMEM127,KPTN|
|ubiquitin-like protein ligase binding|11.21|CUL4A,UBE2G1,UBE2C,TUBB,GLMN,OTUB1|
|negative regulation of intracellular signal transduction|8.08|SZT2,NONO,DEPDC5,HDAC3,TMEM127,CSK,KPTN|
^GO Term^Fold Change^Genes^
|positive regulation of pentose-phosphate shunt|552.70|MLST8,RPTOR|
|tRNA wobble position uridine thiolation|368.47|MOCS3,CTU2|
|tRNA thio-modification|276.35|MOCS3,CTU2|
|COP9 signalosome assembly|276.35|COPS7B,COPS8|
|protein deneddylation|165.81|COPS7B,COPS4,COPS8|
|COP9 signalosome|138.18|COPS7B,COPS2,COPS4,COPS8|
|protein neddylation|100.49|COPS7B,COPS2,COPS4,COPS8|
|positive regulation of purine nucleotide metabolic process|97.54|BEND3,MLST8,RPTOR|
|positive regulation of nucleotide metabolic process|97.54|BEND3,MLST8,RPTOR|
|regulation of protein neddylation|92.12|COPS2,COPS4,COPS8|
|facultative heterochromatin formation|69.09|BEND3,EZH2,SUZ12|
|TOR signaling|47.37|MLST8,RPTOR,MAPKAP1|
|PcG protein complex|46.06|EZH2,SUZ12,EED|
|histone methyltransferase activity|33.50|EZH2,SUZ12,EED,KMT5B|
|protein methyltransferase activity|24.84|EZH2,SUZ12,EED,KMT5B|
|protein modification by small protein removal|19.92|COPS7B,COPS2,COPS4,COPS8|
|protein modification by small protein conjugation|7.40|COPS7B,COPS2,COPS4,UBE2G2,COPS8,WDR24,MOCS3,CTU2,ZNF598|
|protein modification by small protein conjugation or removal|6.51|COPS7B,COPS2,COPS4,UBE2G2,COPS8,WDR24,MOCS3,CTU2,ZNF598|
|post-translational protein modification|5.61|COPS7B,COPS2,COPS4,UBE2G2,COPS8,WDR24,MOCS3,CTU2,ZNF598|