====== PF-06409577 20μM R07 exp389 ======
==== Mechanism of Action ====
Activates AMPK, lowers cholesterol levels in NAFLD/NASH preclinical models
* **Class / Subclass 1:** Signal Transduction / Kinase Activator
==== Technical Notes ====
* **PubChem Name:** %%6-Chloro-5-(4-(1-hydroxycyclobutyl)phenyl)-1H-indole-3-carboxylic acid%%
* **Synonyms:** N/A
* **CAS #:** 1467057-23-3
* **PubChem CID:** [[https://pubchem.ncbi.nlm.nih.gov/compound/71748255|71748255]]
* **IUPAC:** %%6-chloro-5-[4-(1-hydroxycyclobutyl)phenyl]-1H-indole-3-carboxylic acid%%
* **INCHI Name:** InChI=1S/C19H16ClNO3/c20-16-9-17-14(15(10-21-17)18(22)23)8-13(16)11-2-4-12(5-3-11)19(24)6-1-7-19/h2-5,8-10,21,24H,1,6-7H2,(H,22,23)
* **INCHI Key:** FHQXLWCFSUSXBF-UHFFFAOYSA-N
* **Molecular Weight:** 341.8
* **Canonical SMILES:** C1CC(C1)(C2=CC=C(C=C2)C3=C(C=C4C(=C3)C(=CN4)C(=O)O)Cl)O
* **Isomeric SMILES:** N/A
* **Molecular Formula:** C19H16ClNO3
{{:chemogenomics:structures:chem-0231.svg?nolink}}
* **Supplier Name:** Med Chem Express
* **Catalog #:** HY-103683
* **Lot #:** 27233
* **HRMS (ESI-TOF) m/z:** (M+Na)+ Calcd for C19H16ClNO3 364.07109; found 364.07064
* **Platform ID:** PF-06409577
* **Min:** -1.6834; **Max:** 29.3429
{{:chemogenomics:dose_response:dr_396.png?nolink&500 |}}
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^ IC ^ Concentration (µM) ^
| IC10 |N/A |
| IC20 |N/A |
| IC30 |N/A |
| IC40 |N/A |
| IC50 |N/A |
| IC60 |N/A |
| IC70 |N/A |
| IC80 |N/A |
| IC90 |N/A |
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==== Screen Summary ====
* **Round**: 07
* **Dose**: 20µM
* **Days of incubation**: 8
* **Doublings**: 6.1
* **Numbers of reads**: 20658744
==== 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^
|1/10|[[https://files.tyerslab.com/files/public/chemogenomics/cranks/PF-06409577_20uM_Round-7_exp389.txt|Scores]]||||||
{{:chemogenomics:cranks_plots:exp389.png?nolink}}
^Gene^CRANKS Score^FDR^
|[[:human_genes:P:PNMA1|PNMA1]]|-2.94|0.03|
|[[:human_genes:A:AHCYL1|AHCYL1]]|-2.73|0.13|
|[[:human_genes:L:LAMTOR4|LAMTOR4]]|-2.53|0.19|
|[[:human_genes:W:WDR20|WDR20]]|-2.45|0.16|
|[[:human_genes:S:SLC7A11|SLC7A11]]|-2.31|0.23|
|[[:human_genes:M:MCM9|MCM9]]|-2.27|0.31|
|[[:human_genes:P:PLEKHA6|PLEKHA6]]|-2.26|0.23|
|[[:human_genes:P:PRAMEF25|PRAMEF25]]|-2.24|0.68|
|[[:human_genes:Z:ZC3H7B|ZC3H7B]]|-2.24|0.33|
|[[:human_genes:T:TGS1|TGS1]]|-2.23|0.23|
|[[:human_genes:G:GPR152|GPR152]]|-2.23|0.23|
|[[:human_genes:P:PRAMEF26|PRAMEF26]]|-2.23|0.68|
|[[:human_genes:K:KDSR|KDSR]]|-2.21|0.23|
|[[:human_genes:K:KDM6B|KDM6B]]|-2.13|0.38|
|[[:human_genes:P:PRUNE|PRUNE]]|-2.10|0.38|
|[[:human_genes:T:TRIP4|TRIP4]]|-2.07|0.35|
|[[:human_genes:F:FAM64A|FAM64A]]|-2.06|0.35|
|[[:human_genes:N:NAF1|NAF1]]|-2.06|0.35|
|[[:human_genes:S:SESTD1|SESTD1]]|-2.04|0.37|
|[[:human_genes:D:DKC1|DKC1]]|-2.03|0.68|
|[[:human_genes:Z:ZDHHC23|ZDHHC23]]|-2.02|0.38|
|[[:human_genes:M:MTRNR2L9|MTRNR2L9]]|-2.00|0.68|
|[[:human_genes:C:CNBD1|CNBD1]]|-1.98|0.38|
|[[:human_genes:Z:ZSWIM8|ZSWIM8]]|-1.98|0.38|
|[[:human_genes:S:SASH3|SASH3]]|-1.97|0.38|
|[[:human_genes:P:PRPF18|PRPF18]]|-1.96|0.44|
|[[:human_genes:C:CCDC82|CCDC82]]|-1.96|0.44|
|[[:human_genes:G:GGPS1|GGPS1]]|-1.95|0.38|
|[[:human_genes:M:MURC|MURC]]|-1.94|0.38|
|[[:human_genes:C:CMTR2|CMTR2]]|-1.94|0.38|
|[[:human_genes:S:SRD5A3|SRD5A3]]|2.08|0.19|
|[[:human_genes:C:CCL16|CCL16]]|2.11|0.22|
|[[:human_genes:N:NUP160|NUP160]]|2.11|0.36|
|[[:human_genes:D:DRD3|DRD3]]|2.16|0.13|
|[[:human_genes:S:STK38|STK38]]|2.17|0.12|
|[[:human_genes:I:IPMK|IPMK]]|2.17|0.12|
|[[:human_genes:S:SLC25A1|SLC25A1]]|2.18|0.12|
|[[:human_genes:D:DNAJC21|DNAJC21]]|2.20|0.12|
|[[:human_genes:C:CD52|CD52]]|2.22|0.12|
|[[:human_genes:E:EIF4B|EIF4B]]|2.23|0.12|
|[[:human_genes:G:GNA13|GNA13]]|2.24|0.12|
|[[:human_genes:G:G3BP1|G3BP1]]|2.28|0.10|
|[[:human_genes:A:AGBL5|AGBL5]]|2.29|0.22|
|[[:human_genes:B:BMP15|BMP15]]|2.31|0.09|
|[[:human_genes:S:STIL|STIL]]|2.34|0.12|
|[[:human_genes:K:KPNB1|KPNB1]]|2.34|0.45|
|[[:human_genes:R:RIC8A|RIC8A]]|2.36|0.08|
|[[:human_genes:S:SPC25|SPC25]]|2.42|0.32|
|[[:human_genes:M:MSI2|MSI2]]|2.49|0.08|
|[[:human_genes:U:UBE2Q2L|UBE2Q2L]]|2.56|0.47|
|[[:human_genes:I:IPPK|IPPK]]|2.72|0.01|
|[[:human_genes:L:LRRC30|LRRC30]]|2.74|0.03|
|[[:human_genes:D:DEPDC5|DEPDC5]]|2.88|<0.01|
|[[:human_genes:N:NPRL3|NPRL3]]|2.93|0.03|
|[[:human_genes:N:NPRL2|NPRL2]]|3.27|<0.01|
|[[:human_genes:S:STK11|STK11]]|4.77|<0.01|
|[[:human_genes:S:STRADA|STRADA]]|5.37|<0.01|
|[[:human_genes:P:PRKAG1|PRKAG1]]|5.88|<0.01|
|[[:human_genes:P:PRKAA1|PRKAA1]]|6.45|<0.01|
|[[:human_genes:P:PRKAB1|PRKAB1]]|7.12|<0.01|
^Screen^Correlation^Plot^
|[[:results:exp100|NFN1 1μM R03 exp100]]|0.069||
|[[:results:exp510|Nicotine 3000μM R08 exp510]]|0.064||
{{:chemogenomics:comparison_plots:exp100_vs_exp389.png?nolink |}}
{{:chemogenomics:comparison_plots:exp389_vs_exp510.png?nolink |}}
No GO term hits below threshold. (FDR <0.05)
^GO Term^Fold Change^Genes^
|GATOR1 complex|552.63|NPRL2,NPRL3|
|Seh1-associated complex|236.84|NPRL2,NPRL3,DEPDC5|
|cAMP-dependent protein kinase activity|221.05|PRKAA1,PRKAG1|
|negative regulation of TORC1 signaling|67.39|PRKAA1,STK11,NPRL2,NPRL3,DEPDC5|
|negative regulation of TOR signaling|41.87|PRKAA1,STK11,NPRL2,NPRL3,DEPDC5|
|regulation of TORC1 signaling|32.13|PRKAA1,STK11,NPRL2,NPRL3,DEPDC5|
|alcohol biosynthetic process|24.56|PRKAA1,IPPK,IPMK,SRD5A3|
|regulation of TOR signaling|20.47|PRKAA1,STK11,NPRL2,NPRL3,DEPDC5|
|protein kinase complex|18.93|PRKAB1,PRKAA1,PRKAG1,STRADA,STK11|
|positive regulation of autophagy|18.93|PRKAA1,STK11,NPRL2,NPRL3,DEPDC5|
|cellular response to nutrient levels|14.29|PRKAB1,PRKAA1,PRKAG1,NPRL2,NPRL3,DEPDC5|
|cellular response to extracellular stimulus|12.70|PRKAB1,PRKAA1,PRKAG1,NPRL2,NPRL3,DEPDC5|
|cellular response to external stimulus|10.17|PRKAB1,PRKAA1,PRKAG1,NPRL2,NPRL3,DEPDC5|
|small molecule biosynthetic process|8.63|PRKAB1,PRKAA1,PRKAG1,IPPK,SLC25A1,IPMK,SRD5A3|
|negative regulation of intracellular signal transduction|7.54|PRKAA1,STK11,NPRL2,NPRL3,DEPDC5,STK38,DRD3|
|phosphotransferase activity, alcohol group as acceptor|6.54|PRKAB1,PRKAA1,PRKAG1,STRADA,STK11,IPPK,IPMK,STK38|
|phosphorylation|6.13|PRKAB1,PRKAA1,PRKAG1,STRADA,STK11,IPPK,IPMK,STK38|
|kinase activity|6.06|PRKAB1,PRKAA1,PRKAG1,STRADA,STK11,IPPK,IPMK,STK38|