====== Vincristine 0.0005μM R04 exp190 ====== ==== 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:** %%Vincristine sulfate%% * **Synonyms:** Leurocristine sulfate; 22-Oxovincaleukoblastine sulfate * **CAS #:** 2068-78-2 * **PubChem CID:** [[https://pubchem.ncbi.nlm.nih.gov/compound/249332|249332]] * **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]-8-formyl-10-hydroxy-5-methoxy-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/C46H56N4O10.H2O4S/c1-7-42(55)22-28-23-45(40(53)58-5,36-30(14-18-48(24-28)25-42)29-12-9-10-13-33(29)47-36)32-20-31-34(21-35(32)57-4)50(26-51)38-44(31)16-19-49-17-11-15-43(8-2,37(44)49)39(60-27(3)52)46(38,56)41(54)59-6;1-5(2,3)4/h9-13,15,20-21,26,28,37-39,47,55-56H,7-8,14,16-19,22-25H2,1-6H3;(H2,1,2,3,4)/t28-,37+,38-,39-,42+,43-,44-,45+,46+;/m1./s1 * **INCHI Key:** AQTQHPDCURKLKT-JKDPCDLQSA-N * **Molecular Weight:** 923 * **Canonical SMILES:** CCC1(CC2CC(C3=C(CCN(C2)C1)C4=CC=CC=C4N3)(C5=C(C=C6C(=C5)C78CCN9C7C(C=CC9)(C(C(C8N6C=O)(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=O)(C(=O)OC)O)OC(=O)C)CC)OC)C(=O)OC)O.OS(=O)(=O)O * **Molecular Formula:** C46H58N4O14S {{:chemogenomics:structures:chem-0123.svg?nolink}} * **Supplier Name:** Sigma-Aldrich * **Catalog #:** V8879 * **Lot #:** N/A * **LCMS:** Tr 1.08 min, m/z 825+ [M+H]+, 839- [M-H+O]- * **Platform ID:** Vincristine * **Min:** -7.1789; **Max:** 86.5763 {{:chemogenomics:dose_response:dr_251.png?nolink&500 |}} \\ \\ \\ \\ |< 300px 100px 200px >| ^ IC ^ Concentration (µM) ^ | IC10 |N/A | | IC20 |0.0005 | | IC30 |0.0006 | | IC40 |0.0006 | | IC50 |0.0007 | | IC60 |N/A | | IC70 |N/A | | IC80 |N/A | | IC90 |N/A | \\ ==== Screen Summary ==== * **Round**: 04 * **Dose**: 0.5nM * **Days of incubation**: 8 * **Doublings**: 5.2 * **Numbers of reads**: 23430321 ==== 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^ |56/22|[[https://files.tyerslab.com/files/public/chemogenomics/cranks/Vincristine_0.0005uM_Round-4_exp190.txt|Scores]]|||||| {{:chemogenomics:cranks_plots:exp190.png?nolink}} ^Gene^CRANKS Score^FDR^ |[[:human_genes:A:ABCC1|ABCC1]]|-5.09|<0.01| |[[:human_genes:L:LRRC40|LRRC40]]|-4.62|<0.01| |[[:human_genes:A:ATP8B2|ATP8B2]]|-4.29|<0.01| |[[:human_genes:M:MAPRE1|MAPRE1]]|-3.87|<0.01| |[[:human_genes:A:ASPM|ASPM]]|-3.81|<0.01| |[[:human_genes:T:TMEM230|TMEM230]]|-3.62|<0.01| |[[:human_genes:K:KLF16|KLF16]]|-3.62|<0.01| |[[:human_genes:G:GCLM|GCLM]]|-3.37|<0.01| |[[:human_genes:N:NPRL2|NPRL2]]|-3.37|<0.01| |[[:human_genes:D:DLGAP5|DLGAP5]]|-3.23|<0.01| |[[:human_genes:K:KIF15|KIF15]]|-3.22|<0.01| |[[:human_genes:Q:QRICH1|QRICH1]]|-3.22|<0.01| |[[:human_genes:T:TCF4|TCF4]]|-3.19|<0.01| |[[:human_genes:D:DPH1|DPH1]]|-3.19|<0.01| |[[:human_genes:C:CALM2|CALM2]]|-3.16|<0.01| |[[:human_genes:C:CNOT8|CNOT8]]|-3.08|<0.01| |[[:human_genes:K:KCTD5|KCTD5]]|-3.01|<0.01| |[[:human_genes:M:MSI2|MSI2]]|-2.96|<0.01| |[[:human_genes:S:SEPHS1|SEPHS1]]|-2.95|<0.01| |[[:human_genes:T:TMEM127|TMEM127]]|-2.92|<0.01| |[[:human_genes:K:KIFC1|KIFC1]]|-2.89|<0.01| |[[:human_genes:A:ATP2B1|ATP2B1]]|-2.88|<0.01| |[[:human_genes:G:GAK|GAK]]|-2.86|<0.01| |[[:human_genes:Z:ZWILCH|ZWILCH]]|-2.74|<0.01| |[[:human_genes:T:TMEM30A|TMEM30A]]|-2.74|<0.01| |[[:human_genes:R:RSRC2|RSRC2]]|-2.71|0.04| |[[:human_genes:H:HDAC3|HDAC3]]|-2.71|<0.01| |[[:human_genes:C:CENPF|CENPF]]|-2.65|0.01| |[[:human_genes:V:VBP1|VBP1]]|-2.62|<0.01| |[[:human_genes:L:LRP10|LRP10]]|-2.61|0.03| |[[:human_genes:E:EIF3G|EIF3G]]|2.35|0.08| |[[:human_genes:S:SPG21|SPG21]]|2.35|0.08| |[[:human_genes:R:RAB1A|RAB1A]]|2.36|0.04| |[[:human_genes:M:MED17|MED17]]|2.37|0.08| |[[:human_genes:T:TMSB15B|TMSB15B]]|2.41|0.35| |[[:human_genes:R:RAB10|RAB10]]|2.44|0.03| |[[:human_genes:P:PSMD3|PSMD3]]|2.45|0.34| |[[:human_genes:T:TRIP11|TRIP11]]|2.46|0.03| |[[:human_genes:R:RHOB|RHOB]]|2.47|0.03| |[[:human_genes:E:EIF3H|EIF3H]]|2.48|0.05| |[[:human_genes:S:STARD7|STARD7]]|2.54|0.04| |[[:human_genes:P:PACS1|PACS1]]|2.66|0.09| |[[:human_genes:R:RABIF|RABIF]]|2.66|<0.01| |[[:human_genes:D:DEGS1|DEGS1]]|2.71|<0.01| |[[:human_genes:S:STMN1|STMN1]]|2.73|<0.01| |[[:human_genes:M:MANSC4|MANSC4]]|2.81|<0.01| |[[:human_genes:M:MIDN|MIDN]]|2.99|<0.01| |[[:human_genes:H:HSPA5|HSPA5]]|3.03|0.13| |[[:human_genes:X:XAB2|XAB2]]|3.08|0.12| |[[:human_genes:T:TP53BP1|TP53BP1]]|3.10|<0.01| |[[:human_genes:W:WDR37|WDR37]]|3.25|<0.01| |[[:human_genes:R:R3HCC1L|R3HCC1L]]|3.33|<0.01| |[[:human_genes:E:EIF4G2|EIF4G2]]|3.36|<0.01| |[[:human_genes:E:EIF4A1|EIF4A1]]|3.51|<0.01| |[[:human_genes:H:HMGN2|HMGN2]]|3.53|<0.01| |[[:human_genes:D:DDX3X|DDX3X]]|3.62|<0.01| |[[:human_genes:C:CCNF|CCNF]]|3.79|<0.01| |[[:human_genes:N:NUMA1|NUMA1]]|4.19|<0.01| |[[:human_genes:T:TP53|TP53]]|4.86|<0.01| |[[:human_genes:S:SNN|SNN]]|5.05|<0.01| ^Screen^Correlation^Plot^ |[[:results:exp179|Combretastatin A4 0.002 to 0.003μM day4 R04 exp179]]|0.12|| |[[:results:exp184|Ixabepilone 0.004 to 0.005μM on day4 R04 exp184]]|0.117|| |[[:results:exp460|BML-284 0.09μM R08 exp460]]|0.116|| |[[:results:exp228|Demecolcine 0.03μM R05 exp228]]|0.113|| |[[:results:exp215|Colchicine 0.009μM R05 exp215]]|0.112|| |[[:results:exp217|Mdivi-1 15μM R05 exp217]]|0.097|| |[[:results:exp310|2-Methoxyestradiol 0.55μM R07 exp310]]|0.089|| |[[:results:exp312|2-Methoxyestradiol 0.55 to 1μM on day4 R07 exp312]]|0.087|| |[[:results:exp517|Quercetin 20μM R08 exp517]]|0.086|| |[[:results:exp103|Taxol 0.004μM R03 exp103]]|0.084|| |[[:results:exp60|Vinblastine 0.002μM R01 exp60]]|0.081|| |[[:results:exp243|S-trityl-L-cysteine 0.5μM R05 exp243]]|0.079|| |[[:results:exp159|Docetaxel 0.001 to 0.002μM on day4 R04 exp159]]|0.076|| |[[:results:exp45|Docetaxel 0.002μM R01 exp45]]|0.073|| |[[:results:exp59|UMK57 1μM R01 exp59]]|0.07|| |[[:results:exp125|GSK461364A 0.005μM R03 exp125]]|0.07|| |[[:results:exp525|Sulforaphane 9μM R08 exp525]]|0.065|| |[[:results:exp526|Sulforaphane 9μM R08 exp526 no dilution day6]]|0.061|| |[[:results:exp231|Epothilone-B 0.0015μM R05 exp231]]|0.06|| |[[:results:exp177|Apcin 25μM plus proTAME 2μM R04 exp177]]|0.06|| |[[:results:exp311|2-Methoxyestradiol 0.55 to 0.75μM on day4 R07 exp311]]|0.06|| |[[:results:exp97|BI-6727 0.0125μM R03 exp97]]|0.06|| |[[:results:exp210|LB-100 2μM R05 exp210]]|0.059|| |[[:results:exp223|Cabazitaxel 0.001μM R05 exp223]]|0.057|| |[[:results:exp292|Menadione 5μM R06 exp292]]|0.057|| |[[:results:exp480|ETC-159 50μM R08 exp480]]|0.057|| |[[:results:exp95|BI-2536 0.0042μM R03 exp95]]|0.053|| |[[:results:exp240|Pyridostatin 4μM R05 exp240]]|0.053|| |[[:results:exp107|UMK57 0.6μM R03 exp107]]|0.051|| {{:chemogenomics:comparison_plots:exp179_vs_exp190.png?nolink |}} {{:chemogenomics:comparison_plots:exp184_vs_exp190.png?nolink |}} {{:chemogenomics:comparison_plots:exp190_vs_exp460.png?nolink |}} {{:chemogenomics:comparison_plots:exp190_vs_exp228.png?nolink |}} {{:chemogenomics:comparison_plots:exp190_vs_exp215.png?nolink |}} {{:chemogenomics:comparison_plots:exp190_vs_exp217.png?nolink |}} {{:chemogenomics:comparison_plots:exp190_vs_exp310.png?nolink |}} {{:chemogenomics:comparison_plots:exp190_vs_exp312.png?nolink |}} {{:chemogenomics:comparison_plots:exp190_vs_exp517.png?nolink |}} {{:chemogenomics:comparison_plots:exp103_vs_exp190.png?nolink |}} {{:chemogenomics:comparison_plots:exp190_vs_exp60.png?nolink |}} {{:chemogenomics:comparison_plots:exp190_vs_exp243.png?nolink |}} {{:chemogenomics:comparison_plots:exp159_vs_exp190.png?nolink |}} {{:chemogenomics:comparison_plots:exp190_vs_exp45.png?nolink |}} {{:chemogenomics:comparison_plots:exp190_vs_exp59.png?nolink |}} {{:chemogenomics:comparison_plots:exp125_vs_exp190.png?nolink |}} {{:chemogenomics:comparison_plots:exp190_vs_exp525.png?nolink |}} {{:chemogenomics:comparison_plots:exp190_vs_exp526.png?nolink |}} {{:chemogenomics:comparison_plots:exp190_vs_exp231.png?nolink |}} {{:chemogenomics:comparison_plots:exp177_vs_exp190.png?nolink |}} {{:chemogenomics:comparison_plots:exp190_vs_exp311.png?nolink |}} {{:chemogenomics:comparison_plots:exp190_vs_exp97.png?nolink |}} {{:chemogenomics:comparison_plots:exp190_vs_exp210.png?nolink |}} {{:chemogenomics:comparison_plots:exp190_vs_exp223.png?nolink |}} {{:chemogenomics:comparison_plots:exp190_vs_exp292.png?nolink |}} {{:chemogenomics:comparison_plots:exp190_vs_exp480.png?nolink |}} {{:chemogenomics:comparison_plots:exp190_vs_exp95.png?nolink |}} {{:chemogenomics:comparison_plots:exp190_vs_exp240.png?nolink |}} {{:chemogenomics:comparison_plots:exp107_vs_exp190.png?nolink |}} ^GO Term^Fold Change^Genes^ |chromosome localization|25.85|MAPRE1,DLGAP5,KIFC1,CENPF| |spindle assembly|22.53|MAPRE1,ASPM,KIFC1,HDAC3| |spindle pole|18.05|MAPRE1,ASPM,DLGAP5,CALM2,CENPF| |spindle organization|17.74|MAPRE1,ASPM,DLGAP5,KIFC1,HDAC3| |mitotic spindle|17.24|MAPRE1,ASPM,DLGAP5,KIFC1,HDAC3| |nuclear chromosome segregation|13.95|MAPRE1,ASPM,DLGAP5,KIFC1,CENPF| |spindle|13.31|MAPRE1,ASPM,DLGAP5,KIF15,CALM2,KIFC1,ZWILCH,HDAC3,CENPF| |chromosome segregation|11.23|MAPRE1,ASPM,DLGAP5,KIFC1,HDAC3,CENPF| |non-membrane-bounded organelle assembly|10.96|MAPRE1,ASPM,DLGAP5,KIFC1,HDAC3,CENPF| |tubulin binding|10.09|MAPRE1,DLGAP5,KIF15,KIFC1,CENPF,VBP1| |mitotic cell cycle process|8.31|MAPRE1,DLGAP5,CALM2,KIFC1,ZWILCH,HDAC3,CENPF| |organelle localization|8.20|MAPRE1,ASPM,TMEM230,DLGAP5,KIFC1,HDAC3,CENPF| |mitotic cell cycle|8.17|MAPRE1,DLGAP5,KIF15,CALM2,KIFC1,ZWILCH,HDAC3,CENPF| ^GO Term^Fold Change^Genes^ |translation initiation factor activity|45.10|EIF4A1,EIF4G2,EIF3H,EIF3G| |translational initiation|42.50|DDX3X,EIF4A1,EIF4G2,EIF3H,EIF3G|