Hippuristanol 0.12μM R08 exp489 no dilution day6

Hippuristanol 0.12μM R08 exp489 no dilution day6

Mechanism of Action

Inhibits translation by trapping EIF4A on mRNA at poly-purine sites

Class / Subclass 1: Proteostasis / Translation Inhibitor

Technical Notes

Protein References

PubChem Name: Hippuristanol
Synonyms: N/A
CAS #: 80442-78-0
PubChem CID: 9981822
IUPAC: (1S,2S,3'S,4S,6R,7R,8R,9S,11S,12S,13S,16R,18S)-2',2',3',7,9,13-hexamethylspiro[5-oxapentacyclo[10.8.0.02,9.04,8.013,18]icosane-6,5'-oxolane]-7,11,16-triol
INCHI Name: InChI=1S/C28H46O5/c1-15-13-28(33-24(15,2)3)27(6,31)23-21(32-28)12-19-18-8-7-16-11-17(29)9-10-25(16,4)22(18)20(30)14-26(19,23)5/h15-23,29-31H,7-14H2,1-6H3/t15-,16-,17+,18-,19-,20-,21-,22+,23-,25-,26-,27+,28+/m0/s1
INCHI Key: HPHXKNOXVBFETI-SHCCRYCOSA-N
Molecular Weight: 462.7
Canonical SMILES: CC1CC2(C(C3C(O2)CC4C3(CC(C5C4CCC6C5(CCC(C6)O)C)O)C)(C)O)OC1(C)C
Isomeric SMILES: C[C@H]1C[C@]2([C@]([C@H]3[C@@H](O2)C[C@@H]4[C@@]3(C[C@@H]([C@H]5[C@H]4CC[C@@H]6[C@@]5(CC[C@H](C6)O)C)O)C)(C)O)OC1(C)C
Molecular Formula: C28H46O5

Protein Supplier

Supplier Name: In house - McGill University - Jerry Pelletier group
Catalog #: N/A
Lot #: N/A

Protein Characterization

HRMS (ESI-TOF) m/z: (M+Na)+ Calcd for C28H46O5 485.32375; found 485.31999

Dose Response Curve

Platform ID: Hippuristanol
Min: -26.3565; Max: 90.5289

IC	Concentration (µM)
IC10	0.0839
IC20	0.1055
IC30	0.1229
IC40	0.1392
IC50	0.1561
IC60	0.1751
IC70	0.1984
IC80	0.2310
IC90	0.2906

Screen Summary

Round: 08
Dose: 120nM
Days of incubation: 8
Doublings: 2.0
Numbers of reads: 15925511

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
6/124	Scores	View	View	View	View	View

Gene	CRANKS Score	FDR
DDX3X	-3.78	<0.01
SF3B3	-3.18	0.06
KIDINS220	-3.04	<0.01
TSSC1	-2.95	<0.01
FZR1	-2.87	0.02
CHMP2A	-2.82	0.07
SMG5	-2.77	0.28
RANBP1	-2.69	0.02
ARL1	-2.66	0.02
MTF2	-2.58	0.06
SPI1	-2.56	0.06
RSRC2	-2.51	0.36
PKN1	-2.49	0.06
PHACTR4	-2.44	0.06
ZFAND5	-2.41	0.06
NUDT2	-2.39	0.06
TP53BP1	-2.37	0.09
PTPN11	-2.34	0.10
PPP2R2A	-2.34	0.07
RHOA	-2.33	0.07
COPA	-2.26	0.36
BIRC6	-2.26	0.09
ZBTB10	-2.25	0.09
EIF4G2	-2.24	0.09
TIMELESS	-2.22	0.32
UPF3B	-2.21	0.10
ANAPC11	-2.21	0.33
YY1	-2.20	0.25
SCEL	-2.19	0.11
STYX	-2.16	0.19
IKZF1	3.22	0.00
TSC1	3.24	0.00
GNAS	3.24	0.00
HNRNPF	3.28	0.00
PLAA	3.32	0.00
SYK	3.33	0.00
ROMO1	3.33	0.00
EIF4ENIF1	3.36	0.00
TKT	3.36	0.00
CD19	3.49	0.00
SUV420H1	3.55	0.00
BCL2L11	3.57	0.00
TAZ	3.63	<0.01
HDAC3	3.70	0.00
TSC2	3.81	0.00
VDAC2	3.83	0.00
APAF1	3.84	0.00
RICTOR	3.84	0.00
ALAS1	3.86	0.00
MARCH5	4.07	0.00
PIK3CD	4.09	0.00
NPRL3	4.20	0.00
LPAR5	4.22	0.00
CASP9	4.25	0.00
ELP6	4.37	0.00
KLF16	4.53	0.00
MAPKAP1	4.63	0.00
ELP3	4.67	0.00
BAK1	6.40	0.00
EIF4A1	7.64	0.00

Screen	Correlation	Plot
MS023 2μM R03 exp134	0.185	View
MS023 7μM R03 exp135	0.153	View
Staurosporine 0.02μM R08 exp524	0.12	View
Olaparib 4μM R08 exp512	0.117	View
Sulforaphane 9μM R08 exp525	0.098	View
Mitomycin-C 0.06μM R08 exp503	0.092	View
THZ1 0.06μM R08 exp531	0.091	View
Sulforaphane 9μM R08 exp526 no dilution day6	0.085	View
Thimerosal 0.85μM R08 exp529	0.084	View
PU-H71 1μM R08 exp515	0.083	View
Pimelic-diphenylamide-106 5μM R00 exp28	0.08	View
Latrunculin-B 10μM R07 exp374	0.076	View
Tanespimycin 14μM R08 exp527	0.075	View
MLN-4924 0.2μM R00 exp21	0.074	View
Trimetrexate 0.03μM R08 exp535	0.074	View
Milciclib 2μM R08 exp502	0.073	View
SNS-032 15μM R08 exp443	0.071	View
LY2090314 0.003μM R08 exp500 no dilution day6	0.068	View
RO-3307 4.7μM R02 exp80	0.067	View
Lead acetate 2000μM R08 exp497	0.065	View
Tozasertib 0.1μM R07 exp414	0.064	View
JQ1 0.8μM R08 exp435	0.064	View
Lead acetate 2000μM R08 exp498 no dilution day6	0.061	View
UM0129480 7μM R02 exp85	0.06	View
LY2090314 0.003μM R08 exp499	0.059	View
Thapsigargin 0.005μM R07 exp407	0.059	View
Rapamycin 10μM R00 exp30	0.054	View
Nifuroxazide 5μM R03 exp102	0.053	View
QNZ 0.01μM R08 exp439	0.052	View
iCRT14 30μM R08 exp492	0.052	View
Rotenone 20μM R00 exp34	0.052	View
MK2206 4μM R08 exp504	0.051	View
Tubacin 1.6μM R07 exp416	0.051	View
Hippuristanol 0.12μM R08 exp488	0.49	View
Benzoate 20000μM R08 exp456	0.149	View
Aphidicolin 0.4μM R08 exp440	0.138	View
GSK626616 14μM R08 exp485	0.104	View
Ethanol 0.01 R05 exp234	0.104	View
Bleomycin 5μM R08 exp459	0.092	View
CR131-b 0.005μM R08 exp474	0.088	View
Actinomycin-D 0.001μM R00 exp3	0.088	View
AICAR 240μM R03 exp116	0.083	View
Doxorubicin 0.02μM R08 exp478	0.081	View
CI-1040 9.5μM R08 exp472	0.079	View
Artemisinin 50μM R08 exp450	0.078	View
Dorsomorphin 5μM R07 exp357	0.077	View
6-Thio-2-deoxyguanosine 2μM R06 exp259	0.074	View
5-Fluorouracil 20μM R00 exp2	0.074	View
Etoposide 0.3μM R05 exp199	0.072	View
CB-5083 0.4μM R08 exp468	0.07	View
Etoposide 1μM R00 exp19	0.07	View
Arsenate 40μM R06 exp264	0.07	View
Citral 75μM R06 exp275	0.069	View
AICAR 240μM R05 exp211	0.068	View
Erlotinib 10μM R05 exp216	0.067	View
Atovaquone 15μM R08 exp451	0.063	View
Dinaciclib 0.007μM R07 exp355	0.061	View
Amiloride 100μM R08 exp447	0.06	View
∆-9-Tetrahydrocannabinol 30μM R08 exp445	0.06	View
42°C R08 exp539	0.057	View
2-Deoxy-D-glucose 800μM R05 exp214	0.054	View
Ammonium tetrathiomolybdate 10μM R08 exp448	0.052	View
GSK-J4 1.5μM R08 exp441	0.052	View

GO Term	Fold Change	Genes
regulation of cell cycle process	8.54	DDX3X,FZR1,CHMP2A,RANBP1,TP53BP1,PTPN11,RHOA,BIRC6,TIMELESS,ANAPC11

GO Term	Fold Change	Genes
apoptosome	552.30	CASP9,APAF1
activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c	220.92	CASP9,APAF1
porin activity	220.92	BAK1,VDAC2
elongator holoenzyme complex	220.92	ELP3,ELP6
positive regulation of IRE1-mediated unfolded protein response	184.10	BAK1,BCL2L11
TORC2 signaling	184.10	MAPKAP1,RICTOR
tRNA wobble uridine modification	103.56	ELP3,ELP6,KTI12
tRNA wobble base modification	87.21	ELP3,ELP6,KTI12
positive regulation of mitochondrial membrane permeability	59.18	BAK1,VDAC2,BCL2L11
positive regulation of membrane permeability	53.45	BAK1,VDAC2,BCL2L11
TOR signaling	47.34	MAPKAP1,NPRL3,RICTOR
regulation of TORC1 signaling	25.69	NPRL3,TSC2,SYK,TSC1
regulation of TOR signaling	24.55	NPRL3,RICTOR,TSC2,HDAC3,SYK,TSC1
mitochondrial membrane organization	21.04	BAK1,VDAC2,BCL2L11,ROMO1
lymphocyte differentiation	11.67	BAK1,PIK3CD,CD19,SYK,TSC1,IKZF1
mononuclear cell differentiation	10.13	BAK1,PIK3CD,CD19,SYK,TSC1,IKZF1
cellular response to external stimulus	10.13	BAK1,MAPKAP1,NPRL3,RICTOR,TSC2,TSC1
enzyme activator activity	6.82	CASP9,NPRL3,RICTOR,APAF1,TSC2,PLAA,GNAS
hemopoiesis	6.65	BAK1,CASP9,PIK3CD,ALAS1,CD19,SYK,TSC1,IKZF1

Table of Contents

Hippuristanol 0.12μM R08 exp489 no dilution day6

Mechanism of Action

Technical Notes

Protein References

Protein Supplier

Protein Characterization

Dose Response Curve

Screen Summary

Screen Results