Hippuristanol 0.12μM R08 exp488

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

Class / Subclass 1: Proteostasis / Translation Inhibitor

Compound 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

Compound Supplier

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

Compound 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: 0.3
Numbers of reads: 16260685

Sensitive/Resistant hits (FDR<0.05)	CRANKS	Score Plot	Top 30 Genes	Screen Similarity	Top 30 Sensitive GO terms	Top 30 Resistant GO terms
9/126	Scores	View	View	View	View	View

Gene	CRANKS Score	FDR
CHMP2A	-4.14	<0.01
DDX3X	-3.85	<0.01
POLR2L	-3.45	0.18
ARL1	-3.12	<0.01
TCF4	-3.11	<0.01
SPI1	-3.01	<0.01
FZR1	-2.98	<0.01
XPR1	-2.95	<0.01
TSSC1	-2.91	<0.01
SMG5	-2.77	0.25
PSME3	-2.68	0.04
VPS25	-2.47	0.42
SRSF10	-2.45	0.14
YY1	-2.44	0.14
IPO11	-2.44	0.06
PCOLCE2	-2.42	0.09
ZFAND5	-2.41	0.06
RHOA	-2.38	0.07
ACO2	-2.36	0.07
ING1	-2.34	0.07
EIF4G2	-2.30	0.08
KPNB1	-2.29	0.38
MED13	-2.27	0.14
NSA2	-2.26	0.41
NUDT2	-2.26	0.10
TP53BP1	-2.24	0.15
TUBB	-2.24	0.21
AMPD1	-2.22	0.12
PKN1	-2.18	0.13
C16orf46	-2.18	0.23
VDAC2	3.37	0.00
EIF4ENIF1	3.38	0.00
TSC1	3.44	0.00
HNRNPF	3.55	0.00
KTI12	3.55	0.00
SUV420H1	3.58	0.00
PRKACA	3.64	0.00
ROMO1	3.66	0.00
KLF16	3.72	0.00
MOCS3	3.73	0.00
PLAA	3.85	0.00
USP1	3.86	0.00
CEPT1	3.88	0.00
LPAR5	3.93	0.00
HDAC3	3.94	0.00
MARCH5	3.96	0.00
PCBP2	4.02	0.00
SYK	4.06	0.00
ELP6	4.10	0.00
MAPKAP1	4.14	0.00
ALAS1	4.23	0.00
RICTOR	4.27	0.00
CD19	4.27	0.00
PIK3CD	4.27	0.00
BCL2L11	4.29	0.00
TSC2	4.68	0.00
ELP3	4.74	0.00
APAF1	5.20	0.00
BAK1	5.83	0.00
EIF4A1	7.61	0.00

Screen	Correlation	Plot
Hippuristanol 0.12μM R08 exp489 no dilution day6	0.49	View
MS023 2μM R03 exp134	0.162	View
MS023 7μM R03 exp135	0.14	View
Staurosporine 0.02μM R08 exp524	0.118	View
Olaparib 4μM R08 exp512	0.115	View
Mitomycin-C 0.06μM R08 exp503	0.106	View
Trimetrexate 0.03μM R08 exp535	0.099	View
Sulforaphane 9μM R08 exp525	0.096	View
THZ1 0.06μM R08 exp531	0.093	View
Sulforaphane 9μM R08 exp526 no dilution day6	0.092	View
Thimerosal 0.85μM R08 exp529	0.083	View
PU-H71 1μM R08 exp515	0.081	View
Pimelic-diphenylamide-106 5μM R00 exp28	0.08	View
JQ1 0.8μM R08 exp435	0.08	View
iCRT14 30μM R08 exp492	0.077	View
SNS-032 15μM R08 exp443	0.076	View
MLN-4924 0.2μM R00 exp21	0.074	View
UM0129480 7μM R02 exp85	0.069	View
Latrunculin-B 10μM R07 exp374	0.069	View
MK2206 4μM R08 exp504	0.068	View
Thapsigargin 0.005μM R07 exp407	0.068	View
RO-3307 4.7μM R02 exp80	0.066	View
Milciclib 2μM R08 exp502	0.065	View
Pyridostatin 4μM R05 exp240	0.063	View
Rapamycin 10μM R00 exp30	0.063	View
Rotenone 20μM R00 exp34	0.061	View
Tanespimycin 14μM R08 exp527	0.06	View
QNZ 0.01μM R08 exp439	0.059	View
Lead acetate 2000μM R08 exp497	0.057	View
Mubritinib 0.2μM R01 exp48	0.057	View
Lead acetate 2000μM R08 exp498 no dilution day6	0.057	View
Tozasertib 0.1μM R07 exp414	0.056	View
Nifuroxazide 5μM R03 exp102	0.056	View
Nutlin-3A 1.6μM R06 exp294	0.055	View
LY2090314 0.003μM R08 exp500 no dilution day6	0.055	View
Phorbol-12-myristate-13-acetate 0.57μM R08 exp514	0.054	View
Rapamycin 2μM R07 exp306	0.052	View
Oligomycin-A 2μM R00 exp25	0.052	View
Rotenone 0.07μM R08 exp431	0.052	View
Aphidicolin 0.4μM R08 exp440	0.146	View
Benzoate 20000μM R08 exp456	0.142	View
AICAR 240μM R03 exp116	0.102	View
Ethanol 0.01 R05 exp234	0.1	View
GSK626616 14μM R08 exp485	0.096	View
CR131-b 0.005μM R08 exp474	0.091	View
Doxorubicin 0.02μM R08 exp478	0.09	View
CI-1040 9.5μM R08 exp472	0.085	View
Dorsomorphin 5μM R07 exp357	0.084	View
Bleomycin 5μM R08 exp459	0.083	View
Actinomycin-D 0.001μM R00 exp3	0.081	View
Arsenate 40μM R06 exp264	0.08	View
CB-5083 0.4μM R08 exp468	0.079	View
6-Thio-2-deoxyguanosine 2μM R06 exp259	0.077	View
Citral 75μM R06 exp275	0.076	View
Etoposide 0.3μM R05 exp199	0.074	View
Erlotinib 10μM R05 exp216	0.074	View
Artemisinin 50μM R08 exp450	0.074	View
AICAR 240μM R05 exp211	0.073	View
42°C R08 exp539	0.07	View
5-Fluorouracil 20μM R00 exp2	0.07	View
Amiloride 100μM R08 exp447	0.066	View
Etoposide 1μM R00 exp19	0.066	View
Citral 50μM R06 exp274	0.064	View
∆-9-Tetrahydrocannabinol 30μM R08 exp445	0.063	View
Cannabidiol 20μM R08 exp466	0.062	View
Diepoxybutane 3μM R07 exp354	0.062	View
GSK-J4 1.5μM R08 exp441	0.061	View
Dinaciclib 0.007μM R07 exp355	0.06	View
Atovaquone 15μM R08 exp451	0.059	View
Centrinone 0.5μM R07 exp343	0.058	View
2-Deoxy-D-glucose 800μM R05 exp214	0.057	View
Cytochalasin-B 5μM R07 exp349	0.055	View

GO Term	Fold Change	Genes
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	RICTOR,MAPKAP1
tRNA wobble uridine modification	138.07	ELP3,ELP6,MOCS3,KTI12
tRNA wobble base modification	116.27	ELP3,ELP6,MOCS3,KTI12
positive regulation of mitochondrial membrane permeability	59.18	BAK1,BCL2L11,VDAC2
positive regulation of membrane permeability	53.45	BAK1,BCL2L11,VDAC2
neural tube closure	25.10	APAF1,TSC2,PRKACA,TSC1
tRNA modification	24.82	ELP3,ELP6,MOCS3,KTI12
tube closure	24.82	APAF1,TSC2,PRKACA,TSC1
regulation of TOR signaling	24.55	TSC2,RICTOR,SYK,HDAC3,PRKACA,TSC1
primary neural tube formation	23.50	APAF1,TSC2,PRKACA,TSC1
neural tube formation	21.87	APAF1,TSC2,PRKACA,TSC1
mitochondrial membrane organization	21.04	BAK1,BCL2L11,ROMO1,VDAC2
tube formation	19.45	APAF1,TSC2,BCL2L11,PRKACA,TSC1
nuclear transport	11.75	TSC2,SYK,PRKACA,TSC1,EIF4ENIF1

Hippuristanol 0.12μM R08 exp488

Mechanism of Action

Technical Notes

Compound References

Compound Supplier

Compound Characterization

Dose Response Curve

Screen Summary

Screen Results