THZ1 0.06μM R08 exp531

Inhibits CDK7, forms covalent adduct, blocks phosphorylation of the C-terminal domain of RNA polymerase II

Class / Subclass 1: Gene Regulation / Transcription Inhibitor
Class / Subclass 2: Signal Transduction / Kinase Inhibitor

Compound References

PubChem Name: THZ1 Hydrochloride
Synonyms: N/A
CAS #: N/A
PubChem CID: 78358326
IUPAC: N-[3-[[5-chloro-4-(1H-indol-3-yl)pyrimidin-2-yl]amino]phenyl]-4-[[(E)-4-(dimethylamino)but-2-enoyl]amino]benzamide;hydrochloride
INCHI Name: InChI=1S/C31H28ClN7O2.ClH/c1-39(2)16-6-11-28(40)35-21-14-12-20(13-15-21)30(41)36-22-7-5-8-23(17-22)37-31-34-19-26(32)29(38-31)25-18-33-27-10-4-3-9-24(25)27;/h3-15,17-19,33H,16H2,1-2H3,(H,35,40)(H,36,41)(H,34,37,38);1H/b11-6+;
INCHI Key: LSAGMHUBJCPLJS-ICSBZGNSSA-N
Molecular Weight: 602.5
Canonical SMILES: CN(C)CC=CC(=O)NC1=CC=C(C=C1)C(=O)NC2=CC=CC(=C2)NC3=NC=C(C(=N3)C4=CNC5=CC=CC=C54)Cl.Cl
Isomeric SMILES: CN(C)C/C=C/C(=O)NC1=CC=C(C=C1)C(=O)NC2=CC=CC(=C2)NC3=NC=C(C(=N3)C4=CNC5=CC=CC=C54)Cl.Cl
Molecular Formula: C31H29Cl2N7O2

Compound Supplier

Supplier Name: Med Chem Express
Catalog #: HY-80013A
Lot #: 25842

Compound Characterization

HRMS (ESI-TOF) m/z: (M+H)+ Calcd for C31H28ClN7O2 566.20658; found 566.20799

Dose Response Curve

Platform ID: THZ1
Min: -3.2339; Max: 99.8907

IC	Concentration (µM)
IC10	0.0053
IC20	0.0131
IC30	0.0240
IC40	0.0394
IC50	0.0622
IC60	0.0981
IC70	0.1612
IC80	0.2954
IC90	0.7349

Screen Summary

Round: 08
Dose: 60nM
Days of incubation: 8
Doublings: -0.3
Numbers of reads: 16956922

Sensitive/Resistant hits (FDR<0.05)	CRANKS	Score Plot	Top 30 Genes	Screen Similarity	Top 30 Sensitive GO terms	Top 30 Resistant GO terms
0/42	Scores	View	View	View	View	View

Gene	CRANKS Score	FDR
WDR61	-2.73	0.28
POLD2	-2.69	0.28
FANCI	-2.63	0.28
GOLGA6L1	-2.56	0.53
NCLN	-2.54	0.28
PSMA1	-2.45	0.29
EXOSC4	-2.40	0.29
ATP6V1A	-2.34	0.29
UBA1	-2.34	0.52
SPI1	-2.34	0.28
RPS9	-2.28	0.53
HIST1H4E	-2.26	0.28
TAF9	-2.24	0.28
ABCA13	-2.23	0.29
FAM186A	-2.21	0.29
CFLAR	-2.20	0.28
CMC2	-2.18	0.51
CDC73	-2.17	0.36
ZNF121	-2.17	0.28
CHD8	-2.16	0.28
BCOR	-2.15	0.28
FADS6	-2.14	0.39
CDCA8	-2.14	0.51
TRIM36	-2.12	0.29
TAS2R60	-2.09	0.29
UBXN1	-2.08	0.41
PASD1	-2.08	0.29
FPR2	-2.06	0.36
SART1	-2.06	0.53
IL12A	-2.06	0.29
ATP5B	2.51	0.01
TAZ	2.51	0.15
CDH22	2.52	0.02
PARL	2.56	0.02
THG1L	2.60	0.01
DOHH	2.60	0.02
MARCH5	2.60	0.02
C10orf12	2.64	0.02
MLST8	2.70	<0.01
TTI2	2.73	0.01
HSPD1	2.74	<0.01
TP53	2.84	<0.01
TTI1	2.84	<0.01
GNB1L	2.87	<0.01
FBXO11	2.88	<0.01
MED23	2.88	<0.01
CASP9	2.97	<0.01
VDAC2	3.13	<0.01
ALAS1	3.13	0.01
MTOR	3.15	<0.01
KMT2D	3.16	<0.01
RPTOR	3.17	<0.01
TELO2	3.26	<0.01
CYCS	3.41	<0.01
ATP5J	3.53	<0.01
HCCS	3.94	<0.01
APAF1	4.18	<0.01
GMPPB	4.74	<0.01
BAK1	5.68	<0.01
BEND3	7.22	<0.01

Screen	Correlation	Plot
Tanespimycin 14μM R08 exp527	0.089	View
TIC10 10μM R08 exp532	0.06	View
UM131593 0.2μM R03 exp106	0.053	View
Thimerosal 0.85μM R08 exp529	0.052	View
Doxorubicin 0.02μM R08 exp478	0.146	View
SNS-032 15μM R08 exp443	0.146	View
Bleomycin 5μM R08 exp459	0.142	View
Benzoate 20000μM R08 exp456	0.136	View
5-Fluorouracil 20μM R00 exp2	0.128	View
Pimelic-diphenylamide-106 5μM R00 exp28	0.124	View
Mitomycin-C 0.06μM R08 exp503	0.12	View
CI-1040 9.5μM R08 exp472	0.112	View
Actinomycin-D 0.001μM R00 exp3	0.106	View
Etoposide 0.3μM R05 exp199	0.103	View
Atovaquone 15μM R08 exp451	0.099	View
6-Thio-2-deoxyguanosine 2μM R06 exp259	0.096	View
MLN-4924 2μM R00 exp22	0.096	View
Aphidicolin 0.4μM R08 exp440	0.095	View
MS023 7μM R03 exp135	0.094	View
RO-3307 4.7μM R02 exp80	0.093	View
Rotenone 20μM R00 exp34	0.093	View
Hippuristanol 0.12μM R08 exp488	0.093	View
Hippuristanol 0.12μM R08 exp489 no dilution day6	0.091	View
AICAR 240μM R05 exp211	0.09	View
PU-H71 1μM R08 exp515	0.089	View
JQ1 0.8μM R08 exp435	0.086	View
Etoposide 1μM R00 exp19	0.081	View
BI-2536 0.02μM R03 exp96	0.078	View
CR131-b 0.005μM R08 exp474	0.077	View
Staurosporine 0.02μM R08 exp524	0.077	View
Hinokiflavone 12μM R08 exp487	0.075	View
DABN 20μM R00 exp17	0.074	View
Olaparib 4μM R08 exp512	0.074	View
MS023 2μM R03 exp134	0.064	View
Ammonium tetrathiomolybdate 10μM R08 exp448	0.062	View
GSK461364A 0.1μM R03 exp126	0.062	View
BI-6727 0.04μM R03 exp98	0.062	View
GSK626616 14μM R08 exp485	0.061	View
42°C R08 exp539	0.059	View
LY2090314 0.003μM R08 exp500 no dilution day6	0.057	View
GSK-J4 1.5μM R08 exp441	0.057	View
Quercetin 20μM R08 exp517	0.055	View
DABN racemic mixture R03 exp93	0.053	View
Dorsomorphin 5μM R07 exp357	0.052	View

GO Term	Fold Change	Genes
apoptosome	552.30	APAF1,CASP9
positive regulation of pentose-phosphate shunt	552.30	RPTOR,MLST8
TTT complex	552.30	TELO2,TTI1
TORC1 complex	441.84	TELO2,MTOR,TTI1,MLST8
regulation of pentose-phosphate shunt	368.20	RPTOR,MTOR,TP53,MLST8
activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c	331.38	APAF1,CYCS,CASP9
regulation of NADP metabolic process	315.60	RPTOR,MTOR,TP53,MLST8
TOR complex	276.15	TELO2,RPTOR,MTOR,TTI1,MLST8
TORC2 complex	276.15	TELO2,MTOR,TTI1,MLST8
rDNA binding	165.69	BEND3,RPTOR,MTOR
TORC1 signaling	150.63	RPTOR,MTOR,MLST8
positive regulation of purine nucleotide metabolic process	129.95	BEND3,RPTOR,MTOR,MLST8
positive regulation of nucleotide metabolic process	129.95	BEND3,RPTOR,MTOR,MLST8
regulation of purine nucleotide metabolic process	65.75	BEND3,RPTOR,MTOR,TP53,MLST8
regulation of nucleotide metabolic process	64.22	BEND3,RPTOR,MTOR,TP53,MLST8
apoptotic mitochondrial changes	39.45	BAK1,VDAC2,TP53,HSPD1
positive regulation of cysteine-type endopeptidase activity	22.45	BAK1,APAF1,CYCS,CASP9,HSPD1
mitochondrial membrane	9.40	BAK1,HCCS,ATP5PF,CYCS,MTOR,ALAS1,VDAC2,HSPD1,MARCHF5,THG1L,PARL,ATP5F1B
mitochondrial envelope	8.83	BAK1,HCCS,ATP5PF,CYCS,MTOR,ALAS1,VDAC2,HSPD1,MARCHF5,THG1L,PARL,ATP5F1B

THZ1 0.06μM R08 exp531

Mechanism of Action

Technical Notes

Compound References

Compound Supplier

Compound Characterization

Dose Response Curve

Screen Summary

Screen Results