Vinblastine 0.015μM R05 exp208

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: -7.8990; Max: 88.1311

IC	Concentration (µM)
IC10	N/A
IC20	0.0045
IC30	0.0051
IC40	0.0056
IC50	0.0056
IC60	N/A
IC70	0.0079
IC80	N/A
IC90	N/A

Screen Summary

Round: 05
Dose: 15nM
Days of incubation: 8
Doublings: -0.1
Numbers of reads: 20529421

Sensitive/Resistant hits (FDR<0.05)	CRANKS	Score Plot	Top 30 Genes	Screen Similarity	Top 30 Sensitive GO terms	Top 30 Resistant GO terms
0/70	Scores	View	View	View	View	View

Gene	CRANKS Score	FDR
DONSON	-2.57	0.68
ANKRD17	-2.54	0.32
MTCH2	-2.46	0.37
ARCN1	-2.43	0.42
FAM200A	-2.43	0.37
C18orf32	-2.38	0.63
RPL36A-HNRNPH2	-2.37	0.75
AURKB	-2.30	0.57
ATP6V1B2	-2.30	0.42
MTA2	-2.28	0.37
PLK4	-2.27	0.42
PSMD14	-2.27	0.68
PSMA1	-2.26	0.42
LRMP	-2.23	0.42
CADPS	-2.19	0.42
CCDC27	-2.17	0.51
NSF	-2.16	0.57
SACS	-2.16	0.42
NHP2L1	-2.15	0.51
HIVEP3	-2.14	0.51
STAC2	-2.12	0.42
MBTD1	-2.08	0.45
PLCG2	-2.07	0.42
NKIRAS2	-2.07	0.42
CEP290	-2.04	0.42
ZNF275	-2.03	0.42
ATP6V1A	-2.03	0.51
EIF6	-2.02	0.63
FARP2	-2.01	0.42
BCL2L1	-2.01	0.42
CHST12	2.91	<0.01
IQCE	2.99	<0.01
WDR82	3.02	<0.01
CDC20	3.10	<0.01
KLHL7	3.13	<0.01
ZPBP	3.16	<0.01
HOXA13	3.17	<0.01
SNX8	3.18	<0.01
HOXA5	3.21	<0.01
RADIL	3.26	<0.01
LRRC72	3.30	<0.01
SLC29A4	3.34	<0.01
TNRC18	3.37	<0.01
CAMK2B	3.38	<0.01
PELO	3.48	<0.01
BMPER	3.51	<0.01
GNA12	3.54	<0.01
PDE1C	3.64	<0.01
ZWILCH	3.93	<0.01
MAD2L1BP	4.35	<0.01
AMZ1	4.40	<0.01
BUB1B	5.61	<0.01
MAD1L1	5.67	<0.01
MAD2L1	5.87	<0.01
RBM14-RBM4	5.92	<0.01
RBM14	6.54	<0.01
BUB3	6.86	<0.01
ZW10	7.42	<0.01
TRIP13	7.56	<0.01
KNTC1	8.10	<0.01

Screen	Correlation	Plot
Vinblastine 0.2μM R03 exp108	0.057	View
SB743921 0.001μM R05 exp244	0.291	View
Nocodazole 0.2μM R00 exp24	0.245	View
Nocodazole 0.1μM R03 exp94	0.225	View
Rotenone 2μM R00 exp33	0.225	View
Nocodazole 0.2μM R02 exp64	0.19	View
HMS-I1 10μM R06 exp256	0.189	View
DABN racemic mixture R03 exp93	0.185	View
R-DABN 8μM R03 exp111	0.169	View
BI-6727 0.04μM R03 exp98	0.075	View
DABN 20μM R00 exp17	0.074	View

GO Term	Fold Change	Genes
mitotic spindle assembly checkpoint signaling	177.54	KNTC1,TRIP13,ZW10,BUB3,MAD2L1,MAD1L1,BUB1B,ZWILCH,CDC20
mitotic spindle checkpoint signaling	177.54	KNTC1,TRIP13,ZW10,BUB3,MAD2L1,MAD1L1,BUB1B,ZWILCH,CDC20
spindle assembly checkpoint signaling	177.54	KNTC1,TRIP13,ZW10,BUB3,MAD2L1,MAD1L1,BUB1B,ZWILCH,CDC20
negative regulation of mitotic sister chromatid segregation	160.35	KNTC1,TRIP13,ZW10,BUB3,MAD2L1,MAD1L1,BUB1B,ZWILCH,CDC20
negative regulation of mitotic sister chromatid separation	160.35	KNTC1,TRIP13,ZW10,BUB3,MAD2L1,MAD1L1,BUB1B,ZWILCH,CDC20
spindle checkpoint signaling	152.37	KNTC1,TRIP13,ZW10,BUB3,MAD1L1,BUB1B,ZWILCH,CDC20
negative regulation of chromosome segregation	150.64	KNTC1,TRIP13,ZW10,BUB3,MAD2L1,MAD1L1,BUB1B,ZWILCH,CDC20
negative regulation of chromosome separation	150.64	KNTC1,TRIP13,ZW10,BUB3,MAD2L1,MAD1L1,BUB1B,ZWILCH,CDC20
negative regulation of metaphase/anaphase transition of cell cycle	150.64	KNTC1,TRIP13,ZW10,BUB3,MAD2L1,MAD1L1,BUB1B,ZWILCH,CDC20
negative regulation of mitotic metaphase/anaphase transition	142.54	KNTC1,TRIP13,ZW10,MAD2L1,MAD1L1,BUB1B,ZWILCH,CDC20
negative regulation of sister chromatid segregation	142.54	KNTC1,TRIP13,ZW10,BUB3,MAD1L1,BUB1B,ZWILCH,CDC20
negative regulation of nuclear division	108.07	KNTC1,TRIP13,ZW10,BUB3,MAD2L1,MAD1L1,BUB1B,ZWILCH,CDC20
regulation of mitotic sister chromatid segregation	93.79	KNTC1,TRIP13,ZW10,BUB3,MAD2L1,MAD1L1,BUB1B,MAD2L1BP,ZWILCH
regulation of mitotic sister chromatid separation	87.21	TRIP13,ZW10,BUB3,MAD2L1,MAD1L1,BUB1B,MAD2L1BP,ZWILCH,CDC20
regulation of chromosome separation	76.71	KNTC1,TRIP13,ZW10,BUB3,MAD2L1,MAD1L1,BUB1B,MAD2L1BP,ZWILCH,CDC20
regulation of mitotic metaphase/anaphase transition	62.77	KNTC1,TRIP13,ZW10,BUB3,MAD2L1,MAD1L1,BUB1B,MAD2L1BP,ZWILCH,CDC20
regulation of metaphase/anaphase transition of cell cycle	60.70	KNTC1,TRIP13,ZW10,BUB3,MAD2L1,MAD1L1,BUB1B,MAD2L1BP,ZWILCH,CDC20
regulation of mitotic nuclear division	52.38	KNTC1,TRIP13,ZW10,BUB3,MAD2L1,MAD1L1,BUB1B,MAD2L1BP,ZWILCH,HOXA13,CDC20
regulation of nuclear division	42.49	KNTC1,TRIP13,ZW10,BUB3,MAD2L1,MAD1L1,BUB1B,MAD2L1BP,ZWILCH,HOXA13,CDC20

Vinblastine 0.015μM R05 exp208

Mechanism of Action

Technical Notes

Compound References

Compound Supplier

Compound Characterization

Dose Response Curve

Screen Summary

Screen Results