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Ask your administrator if you think this is wrong. ====== Rapamycin 2μM plus Cyclosporin-A 3μM R07 exp307 ====== ==== Mechanism of Action ==== Allosteric mTORC1 inhibitor, forms ternary complex with FKBP12 and mTOR, attenuates protein synthesis and metabolism * **<color #00a2e8>Class / Subclass 1:</color>** Signal Transduction / Kinase Inhibitor * **<color #00a2e8>Class / Subclass 2:</color>** Proteostasis / mTOR inhibitor ==== Technical Notes ==== <accordion collapsed='true'> === Rapamycin === <panel title='Compound References' collapsed='true'> * **<color #00a2e8>PubChem Name:</color>** %%Sirolimus%% * **<color #00a2e8>Synonyms:</color>** Sirolimus; AY 22989 * **<color #00a2e8>CAS #:</color>** 53123-88-9 * **<color #00a2e8>PubChem CID:</color>** [[https://pubchem.ncbi.nlm.nih.gov/compound/5284616|5284616]] * **<color #00a2e8>IUPAC:</color>** %%(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,18-dihydroxy-12-[(2R)-1-[(1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl]propan-2-yl]-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone%% * **<color #00a2e8>INCHI Name:</color>** InChI=1S/C51H79NO13/c1-30-16-12-11-13-17-31(2)42(61-8)28-38-21-19-36(7)51(60,65-38)48(57)49(58)52-23-15-14-18-39(52)50(59)64-43(33(4)26-37-20-22-40(53)44(27-37)62-9)29-41(54)32(3)25-35(6)46(56)47(63-10)45(55)34(5)24-30/h11-13,16-17,25,30,32-34,36-40,42-44,46-47,53,56,60H,14-15,18-24,26-29H2,1-10H3/b13-11+,16-12+,31-17+,35-25+/t30-,32-,33-,34-,36-,37+,38+,39+,40-,42+,43+,44-,46-,47+,51-/m1/s1 * **<color #00a2e8>INCHI Key:</color>** QFJCIRLUMZQUOT-HPLJOQBZSA-N * **<color #00a2e8>Molecular Weight:</color>** 914.2 * **<color #00a2e8>Canonical SMILES:</color>** CC1CCC2CC(C(=CC=CC=CC(CC(C(=O)C(C(C(=CC(C(=O)CC(OC(=O)C3CCCCN3C(=O)C(=O)C1(O2)O)C(C)CC4CCC(C(C4)OC)O)C)C)O)OC)C)C)C)OC * **<color #00a2e8>Isomeric SMILES:</color>** C[C@@H]1CC[C@H]2C[C@@H](/C(=C/C=C/C=C/[C@H](C[C@H](C(=O)[C@@H]([C@@H](/C(=C/[C@H](C(=O)C[C@H](OC(=O)[C@@H]3CCCCN3C(=O)C(=O)[C@@]1(O2)O)[C@H](C)C[C@@H]4CC[C@H]([C@@H](C4)OC)O)C)/C)O)OC)C)C)/C)OC * **<color #00a2e8>Molecular Formula:</color>** C51H79NO13 {{:chemogenomics:structures:chem-0016.svg?nolink}} </panel> <panel title='Compound Supplier' collapsed='true'> * **<color #00a2e8>Supplier Name:</color>** LC Laboratories * **<color #00a2e8>Catalog #:</color>** R-5000 * **<color #00a2e8>Lot #:</color>** ASW-130 </panel> <panel title='Compound Characterization' collapsed='true'> * **<color #00a2e8>HRMS (ESI-TOF) m/z:</color>** (M+Na)+ Calcd for C51H79NO13 936.54436; found 936.54366 </panel> === Cyclosporin A === <panel title='Compound References' collapsed='true'> * **<color #00a2e8>PubChem Name:</color>** %%Cyclosporin A%% * **<color #00a2e8>Synonyms:</color>** Cyclosporine; Ciclosporin * **<color #00a2e8>CAS #:</color>** 59865-13-3 * **<color #00a2e8>PubChem CID:</color>** [[https://pubchem.ncbi.nlm.nih.gov/compound/5284373|5284373]] * **<color #00a2e8>IUPAC:</color>** %%(3S,6S,9S,12R,15S,18S,21S,24S,30S,33S)-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,28-nonamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone%% * **<color #00a2e8>INCHI Name:</color>** InChI=1S/C62H111N11O12/c1-25-27-28-40(15)52(75)51-56(79)65-43(26-2)58(81)67(18)33-48(74)68(19)44(29-34(3)4)55(78)66-49(38(11)12)61(84)69(20)45(30-35(5)6)54(77)63-41(16)53(76)64-42(17)57(80)70(21)46(31-36(7)8)59(82)71(22)47(32-37(9)10)60(83)72(23)50(39(13)14)62(85)73(51)24/h25,27,34-47,49-52,75H,26,28-33H2,1-24H3,(H,63,77)(H,64,76)(H,65,79)(H,66,78)/b27-25+/t40-,41+,42-,43+,44+,45+,46+,47+,49+,50+,51+,52-/m1/s1 * **<color #00a2e8>INCHI Key:</color>** PMATZTZNYRCHOR-CGLBZJNRSA-N * **<color #00a2e8>Molecular Weight:</color>** 1202.6 * **<color #00a2e8>Canonical SMILES:</color>** CCC1C(=O)N(CC(=O)N(C(C(=O)NC(C(=O)N(C(C(=O)NC(C(=O)NC(C(=O)N(C(C(=O)N(C(C(=O)N(C(C(=O)N(C(C(=O)N1)C(C(C)CC=CC)O)C)C(C)C)C)CC(C)C)C)CC(C)C)C)C)C)CC(C)C)C)C(C)C)CC(C)C)C)C * **<color #00a2e8>Isomeric SMILES:</color>** CC[C@H]1C(=O)N(CC(=O)N([C@H](C(=O)N[C@H](C(=O)N([C@H](C(=O)N[C@H](C(=O)N[C@@H](C(=O)N([C@H](C(=O)N([C@H](C(=O)N([C@H](C(=O)N([C@H](C(=O)N1)[C@@H]([C@H](C)C/C=C/C)O)C)C(C)C)C)CC(C)C)C)CC(C)C)C)C)C)CC(C)C)C)C(C)C)CC(C)C)C)C * **<color #00a2e8>Molecular Formula:</color>** C62H111N11O12 {{:chemogenomics:structures:chem-0205.svg?nolink}} </panel> <panel title='Compound Supplier' collapsed='true'> * **<color #00a2e8>Supplier Name:</color>** Sigma-Aldrich * **<color #00a2e8>Catalog #:</color>** 30024 * **<color #00a2e8>Lot #:</color>** 142714V </panel> <panel title='Compound Characterization' collapsed='true'> * **<color #00a2e8>HRMS (ESI-TOF) m/z:</color>** (M+H)+ Calcd for C62H111N11O12 1202.84864; found 1202.84948 </panel> ===Rapamycin+Cyclosporin A=== <panel title='Dose Response Curve' collapsed='true'> * **<color #00a2e8>Platform ID:</color>** CyclosporinA_3uM_Rapamycin * **<color #00a2e8>Min:</color>** 1.4508; **<color #00a2e8>Max:</color>** 90.9009 {{:chemogenomics:dose_response:dr_483.png?nolink&500 |}} \\ \\ \\ \\ |< 300px 100px 200px >| ^ IC ^ Concentration (µM) ^ | IC10 |N/A | | IC20 |3.3691 | | IC30 |4.5493 | | IC40 |5.8239 | | IC50 |7.3402 | | IC60 |N/A | | IC70 |N/A | | IC80 |N/A | | IC90 |N/A | \\ \\ \\ The dose response curve for Rapamycin is also available at: * [[results:exp429|exp429]] * [[results:exp29|exp29]] * [[results:exp30|exp30]] * [[results:exp306|exp306]] The dose response curve for Cyclosporin A is also available at: * [[results:exp347|exp347]] * [[results:exp348|exp348]] </panel> </accordion> ==== Screen Summary ==== * **<color #00a2e8>Round</color>**: 07 * **<color #00a2e8>Dose</color>**: 2µM + 3µM * **<color #00a2e8>Days of incubation</color>**: 8 * **<color #00a2e8>Doublings</color>**: 5.0 * **<color #00a2e8>Numbers of reads</color>**: 17458875 ==== 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^ |8/7|<color #e85500>[[https://files.tyerslab.com/files/public/chemogenomics/cranks/Rapamycin_2uM_Cyclosporin_A_3uM_Round-7_exp307.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="default" size="sm" modal="modal_go_sensitive">View</button>|<button type="default" size="sm" modal="modal_go_resistant">View</button>| <modal id='ScorePlot' size='lg' title='Rapamycin 2μM plus Cyclosporin-A 3μM R07 exp307'> {{:chemogenomics:cranks_plots:exp307.png?nolink}} </modal> <modal id="modal_hits" size="sm" title="Top 30 S/R Genes"> ^Gene^CRANKS Score^FDR^ |[[:human_genes:D:DNAJC3|DNAJC3]]|-3.72|<0.01| |[[:human_genes:D:DERL2|DERL2]]|-3.52|<0.01| |[[:human_genes:R:RPS17L|RPS17L]]|-3.26|0.01| |[[:human_genes:A:ABCC1|ABCC1]]|-2.89|0.02| |[[:human_genes:U:UXS1|UXS1]]|-2.74|0.02| |[[:human_genes:P:PTMS|PTMS]]|-2.70|0.07| |[[:human_genes:I:INTS3|INTS3]]|-2.63|0.10| |[[:human_genes:Z:ZNF608|ZNF608]]|-2.60|0.04| |[[:human_genes:T:TRIP12|TRIP12]]|-2.50|0.05| |[[:human_genes:R:RPS17|RPS17]]|-2.49|0.05| |[[:human_genes:T:TCF4|TCF4]]|-2.43|0.06| |[[:human_genes:Z:ZBTB10|ZBTB10]]|-2.31|0.10| |[[:human_genes:S:SCGB1A1|SCGB1A1]]|-2.28|0.10| |[[:human_genes:I:ID3|ID3]]|-2.27|0.10| |[[:human_genes:S:SCYL1|SCYL1]]|-2.26|0.10| |[[:human_genes:G:GPR173|GPR173]]|-2.26|0.10| |[[:human_genes:W:WIPF1|WIPF1]]|-2.25|0.10| |[[:human_genes:F:FBXW7|FBXW7]]|-2.24|0.10| |[[:human_genes:O:OR6N2|OR6N2]]|-2.23|0.10| |[[:human_genes:F:FLVCR1|FLVCR1]]|-2.18|0.11| |[[:human_genes:T:TAF6L|TAF6L]]|-2.17|0.11| |[[:human_genes:P:PDIA3|PDIA3]]|-2.17|0.11| |[[:human_genes:C:CYLD|CYLD]]|-2.17|0.11| |[[:human_genes:G:GMPPB|GMPPB]]|-2.13|0.48| |[[:human_genes:B:BANF1|BANF1]]|-2.12|0.37| |[[:human_genes:J:JAKMIP3|JAKMIP3]]|-2.12|0.14| |[[:human_genes:S:SLC22A18AS|SLC22A18AS]]|-2.11|0.15| |[[:human_genes:W:WDR82|WDR82]]|-2.10|0.38| |[[:human_genes:C:CBFA2T3|CBFA2T3]]|-2.09|0.16| |[[:human_genes:M:MS4A13|MS4A13]]|-2.07|0.77| |[[:human_genes:P:PEX16|PEX16]]|2.10|0.20| |[[:human_genes:A:ANP32A|ANP32A]]|2.10|0.20| |[[:human_genes:K:KIAA0141|KIAA0141]]|2.10|0.20| |[[:human_genes:T:TP53I13|TP53I13]]|2.12|0.22| |[[:human_genes:A:AGA|AGA]]|2.16|0.19| |[[:human_genes:L:LARP1|LARP1]]|2.16|0.20| |[[:human_genes:T:TMPRSS12|TMPRSS12]]|2.19|0.20| |[[:human_genes:E:ELP5|ELP5]]|2.20|0.20| |[[:human_genes:C:CNBP|CNBP]]|2.22|0.16| |[[:human_genes:H:HK2|HK2]]|2.23|0.31| |[[:human_genes:M:MPHOSPH10|MPHOSPH10]]|2.24|0.24| |[[:human_genes:C:C21orf91|C21orf91]]|2.25|0.20| |[[:human_genes:E:EIF4A1|EIF4A1]]|2.31|0.19| |[[:human_genes:C:COPB2|COPB2]]|2.31|0.38| |[[:human_genes:A:ARID3A|ARID3A]]|2.35|0.20| |[[:human_genes:R:RSF1|RSF1]]|2.41|0.20| |[[:human_genes:C:CDC45|CDC45]]|2.42|0.31| |[[:human_genes:C:CNOT8|CNOT8]]|2.45|0.06| |[[:human_genes:P:PRICKLE1|PRICKLE1]]|2.48|0.05| |[[:human_genes:E:EIF2AK1|EIF2AK1]]|2.57|0.06| |[[:human_genes:T:TRIP10|TRIP10]]|2.59|0.06| |[[:human_genes:S:SCAP|SCAP]]|2.60|0.03| |[[:human_genes:R:RASIP1|RASIP1]]|2.63|0.19| |[[:human_genes:N:NLK|NLK]]|2.70|0.16| |[[:human_genes:C:CRAMP1L|CRAMP1L]]|2.82|<0.01| |[[:human_genes:F:FAM122A|FAM122A]]|3.03|<0.01| |[[:human_genes:G:GSK3B|GSK3B]]|3.17|<0.01| |[[:human_genes:N:NANS|NANS]]|3.23|<0.01| |[[:human_genes:Y:YPEL5|YPEL5]]|3.37|<0.01| |[[:human_genes:F:FKBP1A|FKBP1A]]|5.49|<0.01| </modal> <modal id="modal_screen_similarity" size="lg" title="Correlated Screens"> ^Screen^Correlation^Plot^ |[[:results:exp306|Rapamycin 2μM R07 exp306]]|0.107|<button type="primary" size="small" modal="1">View</button>| |[[:results:exp308|Rapamycin 2μM plus FK-506 5μM R07 exp308]]|0.095|<button type="primary" size="small" modal="2">View</button>| |[[:results:exp30|Rapamycin 10μM R00 exp30]]|0.1|<button type="primary" size="small" modal="3">View</button>| |[[:results:exp29|Rapamycin 1μM R00 exp29]]|0.079|<button type="primary" size="small" modal="4">View</button>| |[[:results:exp429|Rapamycin 0.001μM R08 exp429]]|0.078|<button type="primary" size="small" modal="5">View</button>| |[[:results:exp351|Dexamethasone 0.006μM R07 exp351]]|0.077|<button type="primary" size="small" modal="6">View</button>| |[[:results:exp334|All-trans-Retinoic-Acid 40μM R07 exp334]]|0.065|<button type="primary" size="small" modal="7">View</button>| |[[:results:exp352|Dexamethasone 0.006 to 0.015μM on day4 R07 exp352]]|0.064|<button type="primary" size="small" modal="8">View</button>| |[[:results:exp347|Cyclosporin-A 0.8μM R07 exp347]]|0.064|<button type="primary" size="small" modal="9">View</button>| |[[:results:exp442|Ibrutinib 10μM R08 exp442]]|0.063|<button type="primary" size="small" modal="10">View</button>| |[[:results:exp233|EPZ-5676 30μM R05 exp233]]|0.059|<button type="primary" size="small" modal="11">View</button>| |[[:results:exp242|Radicicol 0.16μM R05 exp242]]|0.055|<button type="primary" size="small" modal="12">View</button>| |[[:results:exp504|MK2206 4μM R08 exp504]]|0.054|<button type="primary" size="small" modal="13">View</button>| |[[:results:exp342|Calcium Ionophore 0.4μM R07 exp342]]|0.052|<button type="primary" size="small" modal="14">View</button>| |[[:results:exp449|Arsenic trioxide 60μM R08 exp449]]|0.051|<button type="primary" size="small" modal="15">View</button>| </modal> <modal id="1" size="lg" title="Rapamycin 2μM plus Cyclosporin-A 3μM R07 exp307 vs Rapamycin 2μM R07 exp306"> {{:chemogenomics:comparison_plots:exp306_vs_exp307.png?nolink |}} </modal> <modal id="2" size="lg" title="Rapamycin 2μM plus Cyclosporin-A 3μM R07 exp307 vs Rapamycin 2μM plus FK-506 5μM R07 exp308"> {{:chemogenomics:comparison_plots:exp307_vs_exp308.png?nolink |}} </modal> <modal id="3" size="lg" title="Rapamycin 10μM R00 exp30 vs Rapamycin 2μM plus Cyclosporin-A 3μM R07 exp307"> {{:chemogenomics:comparison_plots:exp30_vs_exp307.png?nolink |}} </modal> <modal id="4" size="lg" title="Rapamycin 1μM R00 exp29 vs Rapamycin 2μM plus Cyclosporin-A 3μM R07 exp307"> {{:chemogenomics:comparison_plots:exp29_vs_exp307.png?nolink |}} </modal> <modal id="5" size="lg" title="Rapamycin 0.001μM R08 exp429 vs Rapamycin 2μM plus Cyclosporin-A 3μM R07 exp307"> {{:chemogenomics:comparison_plots:exp307_vs_exp429.png?nolink |}} </modal> <modal id="6" size="lg" title="Dexamethasone 0.006μM R07 exp351 vs Rapamycin 2μM plus Cyclosporin-A 3μM R07 exp307"> {{:chemogenomics:comparison_plots:exp307_vs_exp351.png?nolink |}} </modal> <modal id="7" size="lg" title="All-trans-Retinoic-Acid 40μM R07 exp334 vs Rapamycin 2μM plus Cyclosporin-A 3μM R07 exp307"> {{:chemogenomics:comparison_plots:exp307_vs_exp334.png?nolink |}} </modal> <modal id="8" size="lg" title="Dexamethasone 0.006 to 0.015μM on day4 R07 exp352 vs Rapamycin 2μM plus Cyclosporin-A 3μM R07 exp307"> {{:chemogenomics:comparison_plots:exp307_vs_exp352.png?nolink |}} </modal> <modal id="9" size="lg" title="Cyclosporin-A 0.8μM R07 exp347 vs Rapamycin 2μM plus Cyclosporin-A 3μM R07 exp307"> {{:chemogenomics:comparison_plots:exp307_vs_exp347.png?nolink |}} </modal> <modal id="10" size="lg" title="Ibrutinib 10μM R08 exp442 vs Rapamycin 2μM plus Cyclosporin-A 3μM R07 exp307"> {{:chemogenomics:comparison_plots:exp307_vs_exp442.png?nolink |}} </modal> <modal id="11" size="lg" title="EPZ-5676 30μM R05 exp233 vs Rapamycin 2μM plus Cyclosporin-A 3μM R07 exp307"> {{:chemogenomics:comparison_plots:exp233_vs_exp307.png?nolink |}} </modal> <modal id="12" size="lg" title="Radicicol 0.16μM R05 exp242 vs Rapamycin 2μM plus Cyclosporin-A 3μM R07 exp307"> {{:chemogenomics:comparison_plots:exp242_vs_exp307.png?nolink |}} </modal> <modal id="13" size="lg" title="MK2206 4μM R08 exp504 vs Rapamycin 2μM plus Cyclosporin-A 3μM R07 exp307"> {{:chemogenomics:comparison_plots:exp307_vs_exp504.png?nolink |}} </modal> <modal id="14" size="lg" title="Calcium Ionophore 0.4μM R07 exp342 vs Rapamycin 2μM plus Cyclosporin-A 3μM R07 exp307"> {{:chemogenomics:comparison_plots:exp307_vs_exp342.png?nolink |}} </modal> <modal id="15" size="lg" title="Arsenic trioxide 60μM R08 exp449 vs Rapamycin 2μM plus Cyclosporin-A 3μM R07 exp307"> {{:chemogenomics:comparison_plots:exp307_vs_exp449.png?nolink |}} </modal> <modal id="modal_go_sensitive" size="lg" title="Top 30 sensitive GO terms">No GO term hits below threshold. (FDR <0.05)</modal> <modal id="modal_go_resistant" size="lg" title="Top 30 resistant GO terms">No GO term hits below threshold. (FDR <0.05)</modal> Last modified: 2026/01/15 21:36by 127.0.0.1