====== Vinblastine 0.002μM R01 exp60 ======
==== Mechanism of Action ====
Inhibits microtubule polymerization and mitotic spindle formation, induces spindle assembly checkpoint (SAC)
* **Class / Subclass 1:** Cell Cycle / Microtubule Poison
* **Class / Subclass 2:** Organelle Function / Cytoskeletal Inhibitor
==== Technical Notes ====
* **PubChem Name:** %%Vincaleukoblastine sulfate%%
* **Synonyms:** Vincaleukoblastine sulfate salt
* **CAS #:** 143-67-9
* **PubChem CID:** [[https://pubchem.ncbi.nlm.nih.gov/compound/241902|241902]]
* **IUPAC:** %%methyl (1R,9R,10S,11R,12R,19R)-11-acetyloxy-12-ethyl-4-[(13S,15S,17S)-17-ethyl-17-hydroxy-13-methoxycarbonyl-1,11-diazatetracyclo[13.3.1.04,12.05,10]nonadeca-4(12),5,7,9-tetraen-13-yl]-10-hydroxy-5-methoxy-8-methyl-8,16-diazapentacyclo[10.6.1.01,9.02,7.016,19]nonadeca-2,4,6,13-tetraene-10-carboxylate;sulfuric acid%%
* **INCHI Name:** InChI=1S/C46H58N4O9.H2O4S/c1-8-42(54)23-28-24-45(40(52)57-6,36-30(15-19-49(25-28)26-42)29-13-10-11-14-33(29)47-36)32-21-31-34(22-35(32)56-5)48(4)38-44(31)17-20-50-18-12-16-43(9-2,37(44)50)39(59-27(3)51)46(38,55)41(53)58-7;1-5(2,3)4/h10-14,16,21-22,28,37-39,47,54-55H,8-9,15,17-20,23-26H2,1-7H3;(H2,1,2,3,4)/t28-,37+,38-,39-,42+,43-,44-,45+,46+;/m1./s1
* **INCHI Key:** KDQAABAKXDWYSZ-JKDPCDLQSA-N
* **Molecular Weight:** 909.1
* **Canonical SMILES:** CCC1(CC2CC(C3=C(CCN(C2)C1)C4=CC=CC=C4N3)(C5=C(C=C6C(=C5)C78CCN9C7C(C=CC9)(C(C(C8N6C)(C(=O)OC)O)OC(=O)C)CC)OC)C(=O)OC)O.OS(=O)(=O)O
* **Isomeric SMILES:** CC[C@@]1(C[C@@H]2C[C@@](C3=C(CCN(C2)C1)C4=CC=CC=C4N3)(C5=C(C=C6C(=C5)[C@]78CCN9[C@H]7[C@@](C=CC9)([C@H]([C@@]([C@@H]8N6C)(C(=O)OC)O)OC(=O)C)CC)OC)C(=O)OC)O.OS(=O)(=O)O
* **Molecular Formula:** C46H60N4O13S
{{:chemogenomics:structures:chem-0040.svg?nolink}}
* **Supplier Name:** Sigma-Aldrich
* **Catalog #:** V1377
* **Lot #:** N/A
* **HRMS (ESI-TOF) m/z:** (M+H)+ Calcd for C46H58N4O9 811.42766; found 811.42916
* **Platform ID:** VINBLASTINE
* **Min:** -0.8093; **Max:** 78.3626
{{:chemogenomics:dose_response:dr_162.png?nolink&500 |}}
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^ IC ^ Concentration (µM) ^
| IC10 |N/A |
| IC20 |0.0461 |
| IC30 |0.1198 |
| IC40 |0.2622 |
| IC50 |0.5380 |
| IC60 |N/A |
| IC70 |N/A |
| IC80 |N/A |
| IC90 |N/A |
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==== Screen Summary ====
* **Round**: 01
* **Dose**: 2nM
* **Days of incubation**: 8
* **Doublings**: 5.2
* **Numbers of reads**: 15570355
==== 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^
|7/6|[[https://files.tyerslab.com/files/public/chemogenomics/cranks/Vinblastine_0.002uM_Round-1_exp60.txt|Scores]]||||||
{{:chemogenomics:cranks_plots:exp60.png?nolink}}
^Gene^CRANKS Score^FDR^
|[[:human_genes:D:DLGAP5|DLGAP5]]|-3.95|<0.01|
|[[:human_genes:L:LRRC40|LRRC40]]|-3.71|<0.01|
|[[:human_genes:K:KIF15|KIF15]]|-3.53|<0.01|
|[[:human_genes:T:TRIP13|TRIP13]]|-3.34|<0.01|
|[[:human_genes:A:ASPM|ASPM]]|-3.21|0.08|
|[[:human_genes:P:PDS5B|PDS5B]]|-3.14|0.01|
|[[:human_genes:Q:QRICH1|QRICH1]]|-2.86|0.17|
|[[:human_genes:B:BRD1|BRD1]]|-2.74|0.04|
|[[:human_genes:P:PCGF1|PCGF1]]|-2.73|0.04|
|[[:human_genes:I:ITPK1|ITPK1]]|-2.58|0.12|
|[[:human_genes:T:TUBG1|TUBG1]]|-2.56|0.17|
|[[:human_genes:C:CNOT2|CNOT2]]|-2.56|0.12|
|[[:human_genes:K:KIFC1|KIFC1]]|-2.54|0.08|
|[[:human_genes:S:SLIT1|SLIT1]]|-2.49|0.19|
|[[:human_genes:K:KLF16|KLF16]]|-2.49|0.09|
|[[:human_genes:M:MTSS1L|MTSS1L]]|-2.48|0.40|
|[[:human_genes:C:C5AR1|C5AR1]]|-2.42|0.32|
|[[:human_genes:G:GPR83|GPR83]]|-2.42|0.21|
|[[:human_genes:C:CDC23|CDC23]]|-2.42|0.21|
|[[:human_genes:B:BCORL1|BCORL1]]|-2.41|0.32|
|[[:human_genes:T:TCF4|TCF4]]|-2.40|0.12|
|[[:human_genes:C:CXorf64|CXorf64]]|-2.39|0.24|
|[[:human_genes:A:A1BG|A1BG]]|-2.38|0.17|
|[[:human_genes:K:KIF2A|KIF2A]]|-2.35|0.18|
|[[:human_genes:D:DPH1|DPH1]]|-2.34|0.18|
|[[:human_genes:P:PPIL1|PPIL1]]|-2.32|0.29|
|[[:human_genes:N:NSL1|NSL1]]|-2.30|0.30|
|[[:human_genes:A:ARID4B|ARID4B]]|-2.30|0.19|
|[[:human_genes:S:SMAD9|SMAD9]]|-2.28|0.40|
|[[:human_genes:B:BTN2A2|BTN2A2]]|-2.28|0.20|
|[[:human_genes:K:KPNB1|KPNB1]]|2.22|0.47|
|[[:human_genes:P:PHTF1|PHTF1]]|2.22|0.21|
|[[:human_genes:T:TMEM132C|TMEM132C]]|2.24|0.36|
|[[:human_genes:P:PAN2|PAN2]]|2.25|0.29|
|[[:human_genes:S:SLC38A7|SLC38A7]]|2.27|0.28|
|[[:human_genes:N:NUP88|NUP88]]|2.29|0.27|
|[[:human_genes:P:PRPF31|PRPF31]]|2.30|0.43|
|[[:human_genes:I:IFT74|IFT74]]|2.31|0.35|
|[[:human_genes:A:ARHGEF35|ARHGEF35]]|2.32|0.22|
|[[:human_genes:O:ODC1|ODC1]]|2.32|0.19|
|[[:human_genes:P:PREPL|PREPL]]|2.33|0.22|
|[[:human_genes:O:ORC6|ORC6]]|2.38|0.40|
|[[:human_genes:C:C6orf25|C6orf25]]|2.38|0.26|
|[[:human_genes:N:NDE1|NDE1]]|2.41|0.08|
|[[:human_genes:N:NOC3L|NOC3L]]|2.46|0.49|
|[[:human_genes:Z:ZNF280C|ZNF280C]]|2.48|0.19|
|[[:human_genes:D:DTL|DTL]]|2.49|0.22|
|[[:human_genes:S:SAMHD1|SAMHD1]]|2.58|0.15|
|[[:human_genes:T:TMEM161B|TMEM161B]]|2.58|0.08|
|[[:human_genes:K:KIF13A|KIF13A]]|2.58|0.08|
|[[:human_genes:A:AFTPH|AFTPH]]|2.61|0.19|
|[[:human_genes:T:TBCC|TBCC]]|2.63|0.19|
|[[:human_genes:P:PAFAH1B1|PAFAH1B1]]|2.64|0.32|
|[[:human_genes:N:NCR3|NCR3]]|2.64|0.19|
|[[:human_genes:A:ATP1A1|ATP1A1]]|2.88|<0.01|
|[[:human_genes:O:OTUD6B|OTUD6B]]|3.11|<0.01|
|[[:human_genes:N:NUMA1|NUMA1]]|3.22|0.01|
|[[:human_genes:M:MPHOSPH10|MPHOSPH10]]|3.94|0.03|
|[[:human_genes:T:TP53|TP53]]|4.13|<0.01|
|[[:human_genes:A:ATAT1|ATAT1]]|4.40|<0.01|
^Screen^Correlation^Plot^
|[[:results:exp190|Vincristine 0.0005μM R04 exp190]]|0.081||
|[[:results:exp59|UMK57 1μM R01 exp59]]|0.126||
|[[:results:exp460|BML-284 0.09μM R08 exp460]]|0.094||
|[[:results:exp217|Mdivi-1 15μM R05 exp217]]|0.09||
|[[:results:exp228|Demecolcine 0.03μM R05 exp228]]|0.09||
|[[:results:exp46|HMS-I1 1μM R01 exp46]]|0.086||
|[[:results:exp312|2-Methoxyestradiol 0.55 to 1μM on day4 R07 exp312]]|0.078||
|[[:results:exp179|Combretastatin A4 0.002 to 0.003μM day4 R04 exp179]]|0.077||
|[[:results:exp45|Docetaxel 0.002μM R01 exp45]]|0.075||
|[[:results:exp184|Ixabepilone 0.004 to 0.005μM on day4 R04 exp184]]|0.067||
|[[:results:exp517|Quercetin 20μM R08 exp517]]|0.067||
|[[:results:exp54|Taxol 0.002μM R01 exp54]]|0.066||
|[[:results:exp215|Colchicine 0.009μM R05 exp215]]|0.065||
|[[:results:exp310|2-Methoxyestradiol 0.55μM R07 exp310]]|0.059||
|[[:results:exp243|S-trityl-L-cysteine 0.5μM R05 exp243]]|0.058||
|[[:results:exp103|Taxol 0.004μM R03 exp103]]|0.056||
{{:chemogenomics:comparison_plots:exp190_vs_exp60.png?nolink |}}
{{:chemogenomics:comparison_plots:exp59_vs_exp60.png?nolink |}}
{{:chemogenomics:comparison_plots:exp460_vs_exp60.png?nolink |}}
{{:chemogenomics:comparison_plots:exp217_vs_exp60.png?nolink |}}
{{:chemogenomics:comparison_plots:exp228_vs_exp60.png?nolink |}}
{{:chemogenomics:comparison_plots:exp46_vs_exp60.png?nolink |}}
{{:chemogenomics:comparison_plots:exp312_vs_exp60.png?nolink |}}
{{:chemogenomics:comparison_plots:exp179_vs_exp60.png?nolink |}}
{{:chemogenomics:comparison_plots:exp45_vs_exp60.png?nolink |}}
{{:chemogenomics:comparison_plots:exp184_vs_exp60.png?nolink |}}
{{:chemogenomics:comparison_plots:exp517_vs_exp60.png?nolink |}}
{{:chemogenomics:comparison_plots:exp54_vs_exp60.png?nolink |}}
{{:chemogenomics:comparison_plots:exp215_vs_exp60.png?nolink |}}
{{:chemogenomics:comparison_plots:exp310_vs_exp60.png?nolink |}}
{{:chemogenomics:comparison_plots:exp243_vs_exp60.png?nolink |}}
{{:chemogenomics:comparison_plots:exp103_vs_exp60.png?nolink |}}
^GO Term^Fold Change^Genes^
|kinesin complex|41.82|KIF15,KIFC1,KIF2A|
|mitotic sister chromatid segregation|27.46|DLGAP5,TUBG1,KIFC1,CDC23,KIF2A,NSL1|
|sister chromatid segregation|26.67|DLGAP5,TUBG1,KIFC1,CDC23,KIF2A,NSL1|
|mitotic spindle organization|26.67|DLGAP5,TUBG1,KIFC1,KIF2A|
|chromosome localization|26.10|DLGAP5,KIFC1,CDC23,NSL1|
|mitotic nuclear division|22.86|DLGAP5,TUBG1,KIFC1,CDC23,KIF2A,NSL1|
|nuclear chromosome segregation|19.88|DLGAP5,TRIP13,ASPM,TUBG1,KIFC1,CDC23,KIF2A|
|microtubule cytoskeleton organization involved in mitosis|19.32|DLGAP5,TUBG1,KIFC1,KIF2A|
|spindle pole|18.25|DLGAP5,ASPM,TUBG1,KIF2A,NSL1|
|spindle organization|18.15|DLGAP5,ASPM,TUBG1,KIFC1,KIF2A|
|nuclear division|16.36|DLGAP5,TRIP13,ASPM,TUBG1,KIFC1,CDC23,KIF2A,NSL1|
|chromosome segregation|15.14|DLGAP5,TRIP13,ASPM,TUBG1,KIFC1,CDC23,KIF2A,NSL1|
|organelle fission|15.10|DLGAP5,TRIP13,ASPM,TUBG1,KIFC1,CDC23,KIF2A,NSL1|
|chromosome organization|11.20|DLGAP5,TRIP13,PDS5B,TUBG1,KIFC1,CDC23,KIF2A,NSL1|
|spindle|10.40|DLGAP5,KIF15,ASPM,TUBG1,KIFC1,KIF2A,NSL1|
|mitotic cell cycle process|8.39|DLGAP5,TRIP13,TUBG1,KIFC1,CDC23,KIF2A,NSL1|
|mitotic cell cycle|8.23|DLGAP5,KIF15,TRIP13,TUBG1,KIFC1,CDC23,KIF2A,NSL1|
|cell cycle process|6.37|DLGAP5,TRIP13,ASPM,PDS5B,TUBG1,KIFC1,CDC23,KIF2A,NSL1|
^GO Term^Fold Change^Genes^
|establishment of mitotic spindle localization|58.11|NUMA1,PAFAH1B1,NDE1,KPNB1|
|establishment of spindle localization|40.15|NUMA1,PAFAH1B1,NDE1,KPNB1|
|spindle localization|36.80|NUMA1,PAFAH1B1,NDE1,KPNB1|