====== Tunicamycin 0.04 to 0.125μM on day4 R07 exp420 ======
==== Mechanism of Action ====
Inhibits GlcNAc phosphotransferase (GPT), blocks N-linked glycoslylation, induces protein unfolding in ER, nucleoside antibiotic
* **Class / Subclass 1:** Proteostasis / Unfolded Protein Response Activator
* **Class / Subclass 2:** Infectious Disease / Antibiotic
==== Technical Notes ====
* **PubChem Name:** %%Tunicamycin from Streptomyces sp.%%
* **Synonyms:** N/A
* **CAS #:** 11089-65-9
* **PubChem CID:** [[https://pubchem.ncbi.nlm.nih.gov/compound/16220051|16220051]]
* **IUPAC:** %%(E)-N-[(2S,3R,4R,5R,6R)-2-[(2S,3S,4S,5R,6S)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-6-[(2R)-2-[(2R,3S,4R,5R)-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]-2-hydroxyethyl]-4,5-dihydroxyoxan-3-yl]-12-methyltridec-2-enamide%%
* **INCHI Name:** InChI=1S/C37H60N4O16/c1-18(2)12-10-8-6-4-5-7-9-11-13-23(45)39-26-30(50)27(47)21(54-36(26)57-35-25(38-19(3)43)29(49)28(48)22(17-42)55-35)16-20(44)33-31(51)32(52)34(56-33)41-15-14-24(46)40-37(41)53/h11,13-15,18,20-22,25-36,42,44,47-52H,4-10,12,16-17H2,1-3H3,(H,38,43)(H,39,45)(H,40,46,53)/b13-11+/t20-,21-,22+,25+,26-,27+,28+,29+,30-,31+,32-,33-,34-,35+,36+/m1/s1
* **INCHI Key:** YJQCOFNZVFGCAF-WPTOCQRYSA-N
* **Molecular Weight:** 816.9
* **Canonical SMILES:** CC(C)CCCCCCCCC=CC(=O)NC1C(C(C(OC1OC2C(C(C(C(O2)CO)O)O)NC(=O)C)CC(C3C(C(C(O3)N4C=CC(=O)NC4=O)O)O)O)O)O
* **Isomeric SMILES:** CC(C)CCCCCCCC/C=C/C(=O)N[C@@H]1[C@H]([C@H]([C@H](O[C@H]1O[C@H]2[C@H]([C@@H]([C@H]([C@@H](O2)CO)O)O)NC(=O)C)C[C@H]([C@@H]3[C@H]([C@H]([C@@H](O3)N4C=CC(=O)NC4=O)O)O)O)O)O
* **Molecular Formula:** C37H60N4O16
{{:chemogenomics:structures:chem-0251.svg?nolink}}
* **Supplier Name:** Sigma-Aldrich
* **Catalog #:** T7765
* **Lot #:** 037M4047V
* **HRMS (ESI-TOF) m/z:** (M+NH4)+ Calcd for C37H60N4O16 834.43426; found 834.4337
* **Platform ID:** Tunicamycin
* **Min:** -6.5253; **Max:** 80.8037
{{:chemogenomics:dose_response:dr_411.png?nolink&500 |}}
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^ IC ^ Concentration (µM) ^
| IC10 |N/A |
| IC20 |0.0211 |
| IC30 |0.0328 |
| IC40 |0.0492 |
| IC50 |0.0748 |
| IC60 |N/A |
| IC70 |N/A |
| IC80 |N/A |
| IC90 |N/A |
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==== Screen Summary ====
* **Round**: 07
* **Dose**: 0.04-0.125µM
* **Days of incubation**: 8
* **Doublings**: 4.9
* **Numbers of reads**: 15573095
==== 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^
|9/14|[[https://files.tyerslab.com/files/public/chemogenomics/cranks/Tunicamycin_0.04-0.125day4uM_Round-7_exp420.txt|Scores]]||||||
{{:chemogenomics:cranks_plots:exp420.png?nolink}}
^Gene^CRANKS Score^FDR^
|[[:human_genes:D:DPAGT1|DPAGT1]]|-4.40|<0.01|
|[[:human_genes:H:HSP90B1|HSP90B1]]|-3.79|<0.01|
|[[:human_genes:D:DNAJC3|DNAJC3]]|-3.70|<0.01|
|[[:human_genes:C:CXCR4|CXCR4]]|-3.25|<0.01|
|[[:human_genes:N:NANS|NANS]]|-2.89|<0.01|
|[[:human_genes:M:MANF|MANF]]|-2.88|<0.01|
|[[:human_genes:R:RNF149|RNF149]]|-2.73|0.01|
|[[:human_genes:M:MGA|MGA]]|-2.60|0.03|
|[[:human_genes:O:OTUB1|OTUB1]]|-2.58|0.06|
|[[:human_genes:E:ENY2|ENY2]]|-2.55|0.06|
|[[:human_genes:T:THAP1|THAP1]]|-2.52|0.07|
|[[:human_genes:Z:ZBTB1|ZBTB1]]|-2.51|0.04|
|[[:human_genes:Z:ZC3H13|ZC3H13]]|-2.35|0.13|
|[[:human_genes:A:ARL1|ARL1]]|-2.34|0.07|
|[[:human_genes:I:INTS12|INTS12]]|-2.33|0.07|
|[[:human_genes:S:SMC5|SMC5]]|-2.24|0.19|
|[[:human_genes:D:DERL2|DERL2]]|-2.23|0.12|
|[[:human_genes:F:FKBP5|FKBP5]]|-2.18|0.14|
|[[:human_genes:E:EIF3B|EIF3B]]|-2.18|0.61|
|[[:human_genes:I:IRF2BP2|IRF2BP2]]|-2.18|0.14|
|[[:human_genes:D:DHRSX|DHRSX]]|-2.11|0.19|
|[[:human_genes:S:SEPHS1|SEPHS1]]|-2.07|0.22|
|[[:human_genes:T:THEG|THEG]]|-2.06|0.22|
|[[:human_genes:F:FAM228A|FAM228A]]|-2.06|0.22|
|[[:human_genes:S:SUMO2|SUMO2]]|-2.04|0.48|
|[[:human_genes:C:CLEC4F|CLEC4F]]|-2.03|0.24|
|[[:human_genes:A:ALG9|ALG9]]|-2.02|0.25|
|[[:human_genes:Z:ZNF519|ZNF519]]|-2.01|0.38|
|[[:human_genes:Q:QRICH1|QRICH1]]|-1.99|0.44|
|[[:human_genes:N:NOSIP|NOSIP]]|-1.98|0.38|
|[[:human_genes:R:RPN2|RPN2]]|2.18|0.11|
|[[:human_genes:S:SDE2|SDE2]]|2.18|0.11|
|[[:human_genes:C:CTR9|CTR9]]|2.19|0.15|
|[[:human_genes:S:SF1|SF1]]|2.20|0.23|
|[[:human_genes:P:PSMB3|PSMB3]]|2.20|0.36|
|[[:human_genes:K:KPTN|KPTN]]|2.20|0.11|
|[[:human_genes:R:RSF1|RSF1]]|2.21|0.22|
|[[:human_genes:S:SERP2|SERP2]]|2.22|0.10|
|[[:human_genes:P:PRKG2|PRKG2]]|2.24|0.14|
|[[:human_genes:U:UBE2V2|UBE2V2]]|2.25|0.09|
|[[:human_genes:M:MMS19|MMS19]]|2.34|0.15|
|[[:human_genes:U:UBE4B|UBE4B]]|2.37|0.06|
|[[:human_genes:C:CDK8|CDK8]]|2.38|0.09|
|[[:human_genes:A:ACACA|ACACA]]|2.47|0.06|
|[[:human_genes:C:CD79A|CD79A]]|2.48|0.06|
|[[:human_genes:G:GALE|GALE]]|2.50|0.03|
|[[:human_genes:S:SP2|SP2]]|2.61|0.02|
|[[:human_genes:G:GPNMB|GPNMB]]|2.62|0.03|
|[[:human_genes:N:NOL6|NOL6]]|2.71|0.02|
|[[:human_genes:P:PDS5B|PDS5B]]|2.88|<0.01|
|[[:human_genes:D:DRG1|DRG1]]|2.95|<0.01|
|[[:human_genes:M:MGAT1|MGAT1]]|3.08|<0.01|
|[[:human_genes:E:ELF1|ELF1]]|3.25|<0.01|
|[[:human_genes:O:OST4|OST4]]|3.46|0.02|
|[[:human_genes:R:RPL8|RPL8]]|3.50|0.15|
|[[:human_genes:E:EIF2AK3|EIF2AK3]]|3.71|<0.01|
|[[:human_genes:S:SCAP|SCAP]]|3.81|<0.01|
|[[:human_genes:M:MAGT1|MAGT1]]|5.96|<0.01|
|[[:human_genes:S:STT3B|STT3B]]|6.62|<0.01|
|[[:human_genes:M:MFSD2A|MFSD2A]]|8.50|<0.01|
^Screen^Correlation^Plot^
|[[:results:exp418|Tunicamycin 0.04μM R07 exp418]]|0.203||
|[[:results:exp419|Tunicamycin 0.04 to 0.075μM on day4 R07 exp419]]|0.246||
|[[:results:exp407|Thapsigargin 0.005μM R07 exp407]]|0.056||
|[[:results:exp334|All-trans-Retinoic-Acid 40μM R07 exp334]]|0.051||
{{:chemogenomics:comparison_plots:exp418_vs_exp420.png?nolink |}}
{{:chemogenomics:comparison_plots:exp419_vs_exp420.png?nolink |}}
{{:chemogenomics:comparison_plots:exp407_vs_exp420.png?nolink |}}
{{:chemogenomics:comparison_plots:exp334_vs_exp420.png?nolink |}}
No GO term hits below threshold. (FDR <0.05)
^GO Term^Fold Change^Genes^
|oligosaccharyltransferase complex|170.04|STT3B,MAGT1,OST4,RPN2|
|protein N-linked glycosylation via asparagine|120.14|STT3B,MAGT1,OST4,MGAT1,RPN2|
|protein N-linked glycosylation|40.05|STT3B,MAGT1,OST4,MGAT1,RPN2|
|transferase complex|6.01|STT3B,MAGT1,OST4,CDK8,UBE4B,MMS19,UBE2V2,CTR9,RPN2|