Vinblastine 0.2μM R03 exp108

Inhibits microtubule polymerization and mitotic spindle formation, induces spindle assembly checkpoint (SAC)

Class / Subclass 1: Cell Cycle / Microtubule Poison
Class / Subclass 2: Organelle Function / Cytoskeletal Inhibitor

Compound References

PubChem Name: Vincaleukoblastine sulfate
Synonyms: Vincaleukoblastine sulfate salt
CAS #: 143-67-9
PubChem CID: 241902
IUPAC: methyl (1R,9R,10S,11R,12R,19R)-11-acetyloxy-12-ethyl-4-[(13S,15S,17S)-17-ethyl-17-hydroxy-13-methoxycarbonyl-1,11-diazatetracyclo[13.3.1.04,12.05,10]nonadeca-4(12),5,7,9-tetraen-13-yl]-10-hydroxy-5-methoxy-8-methyl-8,16-diazapentacyclo[10.6.1.01,9.02,7.016,19]nonadeca-2,4,6,13-tetraene-10-carboxylate;sulfuric acid
INCHI Name: InChI=1S/C46H58N4O9.H2O4S/c1-8-42(54)23-28-24-45(40(52)57-6,36-30(15-19-49(25-28)26-42)29-13-10-11-14-33(29)47-36)32-21-31-34(22-35(32)56-5)48(4)38-44(31)17-20-50-18-12-16-43(9-2,37(44)50)39(59-27(3)51)46(38,55)41(53)58-7;1-5(2,3)4/h10-14,16,21-22,28,37-39,47,54-55H,8-9,15,17-20,23-26H2,1-7H3;(H2,1,2,3,4)/t28-,37+,38-,39-,42+,43-,44-,45+,46+;/m1./s1
INCHI Key: KDQAABAKXDWYSZ-JKDPCDLQSA-N
Molecular Weight: 909.1
Canonical SMILES: CCC1(CC2CC(C3=C(CCN(C2)C1)C4=CC=CC=C4N3)(C5=C(C=C6C(=C5)C78CCN9C7C(C=CC9)(C(C(C8N6C)(C(=O)OC)O)OC(=O)C)CC)OC)C(=O)OC)O.OS(=O)(=O)O
Isomeric SMILES: CC[C@@]1(C[C@@H]2C[C@@](C3=C(CCN(C2)C1)C4=CC=CC=C4N3)(C5=C(C=C6C(=C5)[C@]78CCN9[C@H]7[C@@](C=CC9)([C@H]([C@@]([C@@H]8N6C)(C(=O)OC)O)OC(=O)C)CC)OC)C(=O)OC)O.OS(=O)(=O)O
Molecular Formula: C46H60N4O13S

Compound Supplier

Supplier Name: Sigma-Aldrich
Catalog #: V1377
Lot #: N/A

Compound Characterization

HRMS (ESI-TOF) m/z: (M+H)+ Calcd for C46H58N4O9 811.42766; found 811.42916

Dose Response Curve

Platform ID: Vinblastine
Min: -0.8093; Max: 78.3626

IC	Concentration (µM)
IC10	N/A
IC20	0.0461
IC30	0.1198
IC40	0.2622
IC50	0.5380
IC60	N/A
IC70	N/A
IC80	N/A
IC90	N/A

Screen Summary

Round: 03
Dose: 200nM
Days of incubation: 8
Doublings: -0.6
Numbers of reads: 10228528

Sensitive/Resistant hits (FDR<0.05)	CRANKS	Score Plot	Top 30 Genes	Screen Similarity	Top 30 Sensitive GO terms	Top 30 Resistant GO terms
0/13	Scores	View	View	View	View	View

Gene	CRANKS Score	FDR
SART1	-2.76	0.74
UNC50	-2.57	0.26
NMRAL1	-2.56	0.35
YTHDC1	-2.34	0.74
PTCH1	-2.22	0.63
LMLN	-2.19	0.58
C10orf111	-2.17	0.58
SEPHS2	-2.16	0.58
ANAPC2	-2.11	0.63
VPS52	-2.10	0.74
TEX13B	-2.07	0.63
TBL1XR1	-2.06	0.63
OLFML2B	-2.05	0.63
MGA	-2.04	0.63
VPS28	-2.02	0.63
MAEA	-2.00	0.63
ATP6V0C	-1.98	0.65
RACGAP1	-1.97	0.63
CCNB1	-1.96	0.63
H2BFWT	-1.94	0.63
L3MBTL2	-1.94	0.63
FCRL2	-1.90	0.63
EBP	-1.89	0.63
ZNF839	-1.89	0.63
TBC1D7	-1.88	0.63
TIMM17B	-1.88	0.63
ZNF335	-1.88	0.74
TSPAN14	-1.88	0.63
TSG101	-1.87	0.63
SRCAP	-1.87	0.63
PP2D1	2.11	0.16
UBE2G2	2.13	0.16
PAM16	2.18	0.17
ATP5O	2.20	0.12
TRIAP1	2.23	0.16
MED13L	2.25	0.16
TTI1	2.25	0.20
PDSS1	2.30	0.19
MOCS3	2.32	0.18
ROMO1	2.32	0.13
PELO	2.33	0.17
PPP6C	2.43	0.08
RPTOR	2.48	0.03
MS4A13	2.54	0.48
DOHH	2.55	0.05
RTCB	2.56	0.16
CYCS	2.57	0.03
TRMT10A	2.60	0.04
QSER1	2.67	0.03
GFPT1	2.92	0.03
BUB3	3.04	0.08
DPAGT1	3.28	0.02
PYROXD1	3.35	0.08
MAD2L1BP	3.40	<0.01
ZW10	3.65	<0.01
MAD1L1	4.41	<0.01
BUB1B	5.74	<0.01
KNTC1	5.88	<0.01
MAD2L1	6.82	<0.01
TRIP13	7.82	<0.01

Screen	Correlation	Plot
GSK461364A 0.1μM R03 exp126	0.141	View
BI-6727 0.04μM R03 exp98	0.128	View
BI-2536 0.02μM R03 exp96	0.119	View
R-DABN 8μM R03 exp111	0.106	View
Ammonium tetrathiomolybdate 10μM R08 exp448	0.091	View
Nocodazole 0.2μM R02 exp64	0.077	View
DABN racemic mixture R03 exp93	0.076	View
DABN 20μM R00 exp17	0.071	View
Benzoate 20000μM R08 exp456	0.068	View
42°C R08 exp539	0.065	View
HMS-I1 10μM R06 exp256	0.065	View
Hinokiflavone 12μM R08 exp487	0.065	View
Etoposide 0.3μM R05 exp199	0.065	View
SNS-032 15μM R08 exp443	0.064	View
CI-1040 9.5μM R08 exp472	0.063	View
6-Thio-2-deoxyguanosine 2μM R06 exp259	0.062	View
Nocodazole 0.2μM R00 exp24	0.06	View
Vinblastine 0.015μM R05 exp208	0.057	View
Nocodazole 0.1μM R03 exp94	0.056	View
Bleomycin 5μM R08 exp459	0.055	View
MLN-4924 2μM R00 exp22	0.054	View
Doxorubicin 0.02μM R08 exp478	0.053	View
Rotenone 2μM R00 exp33	0.052	View
UM131593 0.2μM R03 exp106	0.051	View
TIC10 10μM R08 exp532	0.051	View
PU-H71 1μM R08 exp515	0.051	View
MS023 7μM R03 exp135	0.051	View

GO Term	Fold Change	Genes
spindle assembly checkpoint signaling	138.16	TRIP13,MAD2L1,KNTC1,BUB1B,MAD1L1,ZW10,BUB3
mitotic spindle assembly checkpoint signaling	138.16	TRIP13,MAD2L1,KNTC1,BUB1B,MAD1L1,ZW10,BUB3
mitotic spindle checkpoint signaling	138.16	TRIP13,MAD2L1,KNTC1,BUB1B,MAD1L1,ZW10,BUB3
negative regulation of mitotic sister chromatid separation	124.79	TRIP13,MAD2L1,KNTC1,BUB1B,MAD1L1,ZW10,BUB3
negative regulation of mitotic sister chromatid segregation	124.79	TRIP13,MAD2L1,KNTC1,BUB1B,MAD1L1,ZW10,BUB3
negative regulation of metaphase/anaphase transition of cell cycle	117.23	TRIP13,MAD2L1,KNTC1,BUB1B,MAD1L1,ZW10,BUB3
negative regulation of chromosome segregation	117.23	TRIP13,MAD2L1,KNTC1,BUB1B,MAD1L1,ZW10,BUB3
negative regulation of chromosome separation	117.23	TRIP13,MAD2L1,KNTC1,BUB1B,MAD1L1,ZW10,BUB3
spindle checkpoint signaling	114.34	TRIP13,KNTC1,BUB1B,MAD1L1,ZW10,BUB3
negative regulation of mitotic metaphase/anaphase transition	106.96	TRIP13,MAD2L1,KNTC1,BUB1B,MAD1L1,ZW10
negative regulation of sister chromatid segregation	106.96	TRIP13,KNTC1,BUB1B,MAD1L1,ZW10,BUB3
negative regulation of nuclear division	84.10	TRIP13,MAD2L1,KNTC1,BUB1B,MAD1L1,ZW10,BUB3
regulation of mitotic sister chromatid segregation	83.42	TRIP13,MAD2L1,KNTC1,BUB1B,MAD1L1,ZW10,MAD2L1BP,BUB3
regulation of mitotic sister chromatid separation	66.70	TRIP13,MAD2L1,BUB1B,MAD1L1,ZW10,MAD2L1BP,BUB3
regulation of chromosome separation	60.56	TRIP13,MAD2L1,KNTC1,BUB1B,MAD1L1,ZW10,MAD2L1BP,BUB3
regulation of mitotic metaphase/anaphase transition	49.67	TRIP13,MAD2L1,KNTC1,BUB1B,MAD1L1,ZW10,MAD2L1BP,BUB3
regulation of metaphase/anaphase transition of cell cycle	48.06	TRIP13,MAD2L1,KNTC1,BUB1B,MAD1L1,ZW10,MAD2L1BP,BUB3
regulation of sister chromatid segregation	42.92	TRIP13,MAD2L1,KNTC1,BUB1B,MAD1L1,ZW10,MAD2L1BP,BUB3
regulation of mitotic nuclear division	37.79	TRIP13,MAD2L1,KNTC1,BUB1B,MAD1L1,ZW10,MAD2L1BP,BUB3

Vinblastine 0.2μM R03 exp108

Mechanism of Action

Technical Notes

Compound References

Compound Supplier

Compound Characterization

Dose Response Curve

Screen Summary

Screen Results