====== Mdivi-1 15μM R05 exp217 ======
==== Mechanism of Action ====
Inhibits GTPase dynamin-related protein 1 (Drp1), impairs mitochondrial fission, also inhibits respiratory complex I
* **Class / Subclass 1:** Organelle Function / Mitochondrial Inhibitor
==== Technical Notes ====
* **PubChem Name:** %%3-(2,4-Dichloro-5-methoxyphenyl)-2-sulfanyl-4(3H)-quinazolinone%%
* **Synonyms:** Mitochondrial division inhibitor 1
* **CAS #:** 338967-87-6
* **PubChem CID:** [[https://pubchem.ncbi.nlm.nih.gov/compound/3825829|3825829]]
* **IUPAC:** %%3-(2,4-dichloro-5-methoxyphenyl)-2-sulfanylidene-1H-quinazolin-4-one%%
* **INCHI Name:** InChI=1S/C15H10Cl2N2O2S/c1-21-13-7-12(9(16)6-10(13)17)19-14(20)8-4-2-3-5-11(8)18-15(19)22/h2-7H,1H3,(H,18,22)
* **INCHI Key:** NZJKEVWTYMOYOR-UHFFFAOYSA-N
* **Molecular Weight:** 353.2
* **Canonical SMILES:** COC1=C(C=C(C(=C1)N2C(=O)C3=CC=CC=C3NC2=S)Cl)Cl
* **Isomeric SMILES:** N/A
* **Molecular Formula:** C15H10Cl2N2O2S
{{:chemogenomics:structures:chem-0119.svg?nolink}}
* **Supplier Name:** Sigma-Aldrich
* **Catalog #:** M0199
* **Lot #:** N/A
* **HRMS (ESI-TOF) m/z:** (M+H)+ Calcd for C15H10Cl2N2O2S 352.99128; found 352.99118
* **Platform ID:** Mdivi-1
* **Min:** -12.2946; **Max:** 89.1505
{{:chemogenomics:dose_response:dr_230.png?nolink&500 |}}
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^ IC ^ Concentration (µM) ^
| IC10 |N/A |
| IC20 |11.9377 |
| IC30 |14.5586 |
| IC40 |17.1308 |
| IC50 |19.8894 |
| IC60 |N/A |
| IC70 |N/A |
| IC80 |N/A |
| IC90 |N/A |
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==== Screen Summary ====
* **Round**: 05
* **Dose**: 15µM
* **Days of incubation**: 8
* **Doublings**: 4.8
* **Numbers of reads**: 17266778
==== 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^
|38/66|[[https://files.tyerslab.com/files/public/chemogenomics/cranks/Mdivi-1_15uM_Round-5_exp217.txt|Scores]]||||||
{{:chemogenomics:cranks_plots:exp217.png?nolink}}
^Gene^CRANKS Score^FDR^
|[[:human_genes:Y:YPEL5|YPEL5]]|-4.80|<0.01|
|[[:human_genes:S:SGOL2|SGOL2]]|-4.42|<0.01|
|[[:human_genes:T:TCF4|TCF4]]|-3.88|<0.01|
|[[:human_genes:T:TRIP13|TRIP13]]|-3.84|<0.01|
|[[:human_genes:A:ASPM|ASPM]]|-3.61|<0.01|
|[[:human_genes:S:SEPHS1|SEPHS1]]|-3.48|<0.01|
|[[:human_genes:C:CALM2|CALM2]]|-3.39|<0.01|
|[[:human_genes:E:EDF1|EDF1]]|-3.37|<0.01|
|[[:human_genes:K:KNTC1|KNTC1]]|-3.31|<0.01|
|[[:human_genes:T:TSC1|TSC1]]|-3.28|<0.01|
|[[:human_genes:B:BRD1|BRD1]]|-3.21|<0.01|
|[[:human_genes:C:CNOT8|CNOT8]]|-3.18|<0.01|
|[[:human_genes:M:MSI2|MSI2]]|-3.06|<0.01|
|[[:human_genes:T:TUBB4B|TUBB4B]]|-2.97|<0.01|
|[[:human_genes:T:TACC3|TACC3]]|-2.93|<0.01|
|[[:human_genes:W:WDR26|WDR26]]|-2.93|<0.01|
|[[:human_genes:K:KIF18A|KIF18A]]|-2.89|<0.01|
|[[:human_genes:Q:QRICH1|QRICH1]]|-2.89|0.01|
|[[:human_genes:G:GTSE1|GTSE1]]|-2.86|<0.01|
|[[:human_genes:Z:ZWILCH|ZWILCH]]|-2.72|<0.01|
|[[:human_genes:D:DNTTIP1|DNTTIP1]]|-2.71|<0.01|
|[[:human_genes:T:TSC2|TSC2]]|-2.70|<0.01|
|[[:human_genes:G:GSK3B|GSK3B]]|-2.67|<0.01|
|[[:human_genes:E:ESCO2|ESCO2]]|-2.67|<0.01|
|[[:human_genes:C:CDK2|CDK2]]|-2.65|<0.01|
|[[:human_genes:A:ATP2B1|ATP2B1]]|-2.59|0.02|
|[[:human_genes:U:UBE4B|UBE4B]]|-2.56|0.01|
|[[:human_genes:P:PPIL1|PPIL1]]|-2.55|0.02|
|[[:human_genes:M:MAPRE1|MAPRE1]]|-2.51|0.03|
|[[:human_genes:P:PSME4|PSME4]]|-2.49|0.03|
|[[:human_genes:H:HAUS6|HAUS6]]|2.74|<0.01|
|[[:human_genes:T:TMEM161B|TMEM161B]]|2.75|<0.01|
|[[:human_genes:M:MEF2C|MEF2C]]|2.78|<0.01|
|[[:human_genes:C:CBX3|CBX3]]|2.80|<0.01|
|[[:human_genes:P:PPP2R5C|PPP2R5C]]|2.80|<0.01|
|[[:human_genes:T:TIPRL|TIPRL]]|2.83|<0.01|
|[[:human_genes:P:PPP1CC|PPP1CC]]|2.84|<0.01|
|[[:human_genes:N:NSD1|NSD1]]|2.85|<0.01|
|[[:human_genes:S:SNRK|SNRK]]|2.87|<0.01|
|[[:human_genes:C:CELF1|CELF1]]|2.97|<0.01|
|[[:human_genes:K:KATNA1|KATNA1]]|2.97|<0.01|
|[[:human_genes:S:SEC63|SEC63]]|2.98|<0.01|
|[[:human_genes:D:DCUN1D1|DCUN1D1]]|3.01|<0.01|
|[[:human_genes:P:PHF15|PHF15]]|3.04|<0.01|
|[[:human_genes:A:ATAT1|ATAT1]]|3.09|<0.01|
|[[:human_genes:P:PPME1|PPME1]]|3.24|<0.01|
|[[:human_genes:K:KIF2A|KIF2A]]|3.25|<0.01|
|[[:human_genes:T:TUBB|TUBB]]|3.70|<0.01|
|[[:human_genes:K:KATNB1|KATNB1]]|3.92|<0.01|
|[[:human_genes:N:NUMA1|NUMA1]]|4.12|<0.01|
|[[:human_genes:C:CLASP1|CLASP1]]|4.23|<0.01|
|[[:human_genes:H:HAUS3|HAUS3]]|4.27|<0.01|
|[[:human_genes:C:CCNF|CCNF]]|4.29|<0.01|
|[[:human_genes:P:PPP2R1A|PPP2R1A]]|4.53|<0.01|
|[[:human_genes:C:CLASP2|CLASP2]]|4.86|<0.01|
|[[:human_genes:K:KIF4A|KIF4A]]|4.97|<0.01|
|[[:human_genes:T:TP53|TP53]]|5.44|<0.01|
|[[:human_genes:K:KIF2C|KIF2C]]|5.88|<0.01|
|[[:human_genes:L:LCMT1|LCMT1]]|6.45|<0.01|
|[[:human_genes:K:KIF18B|KIF18B]]|7.96|<0.01|
^Screen^Correlation^Plot^
|[[:results:exp59|UMK57 1μM R01 exp59]]|0.216||
|[[:results:exp106|UM131593 0.2μM R03 exp106]]|0.133||
|[[:results:exp103|Taxol 0.004μM R03 exp103]]|0.104||
|[[:results:exp190|Vincristine 0.0005μM R04 exp190]]|0.097||
|[[:results:exp517|Quercetin 20μM R08 exp517]]|0.095||
|[[:results:exp60|Vinblastine 0.002μM R01 exp60]]|0.09||
|[[:results:exp80|RO-3307 4.7μM R02 exp80]]|0.066||
|[[:results:exp107|UMK57 0.6μM R03 exp107]]|0.059||
|[[:results:exp243|S-trityl-L-cysteine 0.5μM R05 exp243]]|0.058||
|[[:results:exp294|Nutlin-3A 1.6μM R06 exp294]]|0.054||
|[[:results:exp502|Milciclib 2μM R08 exp502]]|0.051||
|[[:results:exp460|BML-284 0.09μM R08 exp460]]|0.207||
|[[:results:exp312|2-Methoxyestradiol 0.55 to 1μM on day4 R07 exp312]]|0.121||
|[[:results:exp228|Demecolcine 0.03μM R05 exp228]]|0.12||
|[[:results:exp67|BVD-523 15μM R02 exp67]]|0.118||
|[[:results:exp311|2-Methoxyestradiol 0.55 to 0.75μM on day4 R07 exp311]]|0.105||
|[[:results:exp215|Colchicine 0.009μM R05 exp215]]|0.098||
|[[:results:exp179|Combretastatin A4 0.002 to 0.003μM day4 R04 exp179]]|0.097||
|[[:results:exp46|HMS-I1 1μM R01 exp46]]|0.085||
|[[:results:exp310|2-Methoxyestradiol 0.55μM R07 exp310]]|0.084||
|[[:results:exp184|Ixabepilone 0.004 to 0.005μM on day4 R04 exp184]]|0.083||
|[[:results:exp231|Epothilone-B 0.0015μM R05 exp231]]|0.065||
|[[:results:exp97|BI-6727 0.0125μM R03 exp97]]|0.061||
|[[:results:exp45|Docetaxel 0.002μM R01 exp45]]|0.051||
{{:chemogenomics:comparison_plots:exp217_vs_exp59.png?nolink |}}
{{:chemogenomics:comparison_plots:exp106_vs_exp217.png?nolink |}}
{{:chemogenomics:comparison_plots:exp103_vs_exp217.png?nolink |}}
{{:chemogenomics:comparison_plots:exp190_vs_exp217.png?nolink |}}
{{:chemogenomics:comparison_plots:exp217_vs_exp517.png?nolink |}}
{{:chemogenomics:comparison_plots:exp217_vs_exp60.png?nolink |}}
{{:chemogenomics:comparison_plots:exp217_vs_exp80.png?nolink |}}
{{:chemogenomics:comparison_plots:exp107_vs_exp217.png?nolink |}}
{{:chemogenomics:comparison_plots:exp217_vs_exp243.png?nolink |}}
{{:chemogenomics:comparison_plots:exp217_vs_exp294.png?nolink |}}
{{:chemogenomics:comparison_plots:exp217_vs_exp502.png?nolink |}}
{{:chemogenomics:comparison_plots:exp217_vs_exp460.png?nolink |}}
{{:chemogenomics:comparison_plots:exp217_vs_exp312.png?nolink |}}
{{:chemogenomics:comparison_plots:exp217_vs_exp228.png?nolink |}}
{{:chemogenomics:comparison_plots:exp217_vs_exp67.png?nolink |}}
{{:chemogenomics:comparison_plots:exp217_vs_exp311.png?nolink |}}
{{:chemogenomics:comparison_plots:exp215_vs_exp217.png?nolink |}}
{{:chemogenomics:comparison_plots:exp179_vs_exp217.png?nolink |}}
{{:chemogenomics:comparison_plots:exp217_vs_exp46.png?nolink |}}
{{:chemogenomics:comparison_plots:exp217_vs_exp310.png?nolink |}}
{{:chemogenomics:comparison_plots:exp184_vs_exp217.png?nolink |}}
{{:chemogenomics:comparison_plots:exp217_vs_exp231.png?nolink |}}
{{:chemogenomics:comparison_plots:exp217_vs_exp97.png?nolink |}}
{{:chemogenomics:comparison_plots:exp217_vs_exp45.png?nolink |}}
^GO Term^Fold Change^Genes^
|kinetochore microtubule|95.23|KNTC1,KIF18A,ZWILCH|
|mitotic spindle checkpoint signaling|61.22|TRIP13,KNTC1,ZWILCH|
|mitotic spindle assembly checkpoint signaling|61.22|TRIP13,KNTC1,ZWILCH|
|spindle assembly checkpoint signaling|61.22|TRIP13,KNTC1,ZWILCH|
|spindle checkpoint signaling|59.11|TRIP13,KNTC1,ZWILCH|
|spindle microtubule|36.63|CALM2,KNTC1,KIF18A,ZWILCH,MAPRE1|
|cytoplasmic microtubule|27.21|TUBB4B,KIF18A,GTSE1,MAPRE1|
|mitotic cell cycle checkpoint signaling|23.42|TRIP13,KNTC1,GTSE1,ZWILCH,CDK2|
|spindle pole|20.17|YPEL5,ASPM,CALM2,KNTC1,TACC3,MAPRE1|
|mitotic spindle|19.37|YPEL5,ASPM,TUBB4B,TACC3,KIF18A,MAPRE1|
|cell cycle checkpoint signaling|18.31|TRIP13,KNTC1,GTSE1,ZWILCH,CDK2|
|spindle|12.42|YPEL5,ASPM,CALM2,KNTC1,TUBB4B,TACC3,KIF18A,ZWILCH,MAPRE1|
|chromosome segregation|12.23|SGO2,TRIP13,ASPM,KNTC1,KIF18A,ESCO2,MAPRE1|
|microtubule|10.53|ASPM,CALM2,KNTC1,TUBB4B,KIF18A,GTSE1,ZWILCH,MAPRE1|
|mitotic cell cycle process|9.93|TRIP13,CALM2,KNTC1,TACC3,KIF18A,GTSE1,ZWILCH,CDK2,MAPRE1|
|mitotic cell cycle|9.49|TRIP13,CALM2,KNTC1,TUBB4B,TACC3,KIF18A,GTSE1,ZWILCH,CDK2,MAPRE1|
|cell division|7.90|SGO2,ASPM,KNTC1,TACC3,ZWILCH,CDK2,MAPRE1|
|cell cycle process|7.85|SGO2,TRIP13,ASPM,CALM2,KNTC1,TACC3,KIF18A,GTSE1,ZWILCH,ESCO2,CDK2,MAPRE1|
|polymeric cytoskeletal fiber|6.92|ASPM,CALM2,KNTC1,TSC1,TUBB4B,KIF18A,GTSE1,ZWILCH,MAPRE1|
^GO Term^Fold Change^Genes^
|spindle microtubule|56.65|KIF18B,KIF4A,CLASP2,HAUS3,CLASP1,NUMA1,KIF2A,HAUS6|
|spindle assembly|35.47|KIF4A,CLASP2,HAUS3,CLASP1,NUMA1,KIF2A,HAUS6|
|mitotic sister chromatid segregation|32.49|KIF18B,KIF2C,KIF4A,CLASP2,PPP2R1A,CLASP1,KATNB1,KIF2A|
|sister chromatid segregation|31.56|KIF18B,KIF2C,KIF4A,CLASP2,PPP2R1A,CLASP1,KATNB1,KIF2A|
|spindle organization|28.90|KIF4A,CLASP2,PPP2R1A,HAUS3,CLASP1,NUMA1,TUBB,KIF2A,HAUS6|
|mitotic spindle|28.08|KIF18B,CLASP2,HAUS3,CLASP1,NUMA1,TUBB,ATAT1,KATNA1,HAUS6|
|microtubule binding|20.84|KIF18B,KIF2C,KIF4A,CLASP2,CLASP1,NUMA1,KATNB1,KIF2A,KATNA1,HAUS6|
|chromosome segregation|20.27|KIF18B,KIF2C,KIF4A,CLASP2,PPP2R1A,HAUS3,CLASP1,NUMA1,KATNB1,TUBB,KIF2A,HAUS6|
|nuclear chromosome segregation|20.18|KIF18B,KIF2C,KIF4A,CLASP2,PPP2R1A,CLASP1,KATNB1,KIF2A|
|spindle|18.68|KIF18B,KIF2C,KIF4A,CLASP2,HAUS3,CLASP1,NUMA1,KATNB1,TUBB,KIF2A,ATAT1,KATNA1,CBX3,HAUS6|
|microtubule|16.54|KIF18B,KIF2C,KIF4A,CLASP2,HAUS3,CLASP1,NUMA1,KATNB1,TUBB,KIF2A,ATAT1,KATNA1,HAUS6|
|cell division|15.28|KIF18B,KIF2C,KIF4A,CLASP2,CCNF,HAUS3,CLASP1,NUMA1,KATNB1,TUBB,KIF2A,KATNA1,PPP1CC,HAUS6|
|tubulin binding|15.09|KIF18B,KIF2C,KIF4A,CLASP2,CLASP1,NUMA1,KATNB1,KIF2A,KATNA1,HAUS6|
|microtubule cytoskeleton organization|14.35|KIF18B,KIF2C,KIF4A,CLASP2,PPP2R1A,HAUS3,CLASP1,NUMA1,KATNB1,TUBB,KIF2A,ATAT1,KATNA1,HAUS6|
|mitotic cell cycle process|13.86|KIF18B,LCMT1,KIF2C,TP53,KIF4A,CLASP2,PPP2R1A,CCNF,CLASP1,NUMA1,KATNB1,KIF2A,PPME1|
|mitotic cell cycle|12.84|KIF18B,LCMT1,KIF2C,TP53,KIF4A,CLASP2,PPP2R1A,CCNF,CLASP1,NUMA1,KATNB1,TUBB,KIF2A,PPME1|
|cell cycle process|10.11|KIF18B,LCMT1,KIF2C,TP53,KIF4A,CLASP2,PPP2R1A,CCNF,HAUS3,CLASP1,NUMA1,KATNB1,TUBB,KIF2A,PPME1,HAUS6|
|microtubule-based process|9.91|KIF18B,KIF2C,KIF4A,CLASP2,PPP2R1A,HAUS3,CLASP1,NUMA1,KATNB1,TUBB,KIF2A,ATAT1,KATNA1,HAUS6|
|polymeric cytoskeletal fiber|9.66|KIF18B,KIF2C,KIF4A,CLASP2,HAUS3,CLASP1,NUMA1,KATNB1,TUBB,KIF2A,ATAT1,KATNA1,HAUS6|