Compound Detail

CHEMBL4226570

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Cc1ncsc1-c1ccc(CNC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)COCCOCCOCCNC(=O)C[C@@H]2N=C(c3ccc(Cl)cc3)c3c(sc(C)c3C)-n3c(C)nnc32)C(C)(C)C)cc1

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL4226570
Phase	Preclinical
Structure Type	MOL
InChI Key	PTAMRJLIOCHJMQ-PYNGZGNASA-N

Targets

Activities

Assay Types

PK Parameters

Publications

Known Names

Molecular Properties

1002.7

MW (Da)

Drug Information

Molecule Type	Small molecule
Availability	Unknown
Chirality	Unknown

Flags

First in Class Prodrug Chemical Probe

Extended Properties

Molecular Formula	C49H60ClN9O8S2
MW	1002.66

Activity Summary

Kd 17 meas. best 8.05

IC50 10 meas. best 8.82

Ki 7 meas. best 7.04

EC50 6 meas. best 7.57

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
EOL1 CHEMBL614489	IC50	8.82	8.82	1.5	1
HL-60 CHEMBL383	IC50	8.82	8.82	1.5	1
von Hippel-Lindau disease tumor suppressor/Elongin-B/Elongin-C/Bromodomain-containing protein 4 CHEMBL4296148	Kd	8.05	8.05	9.0	1
MV4-11 CHEMBL613835	IC50	7.95	7.95	11.3	1
Bromodomain-containing protein 4 CHEMBL1163125	Kd	7.58	6.798	26.0	5
MV4-11 CHEMBL613835	EC50	7.57	7.2567	26.9	3
von Hippel-Lindau disease tumor suppressor CHEMBL3108660	Kd	7.47	7.325	34.0	2
von Hippel-Lindau disease tumor suppressor/Bromodomain-containing protein 4 CHEMBL4296140	Kd	7.41	7.41	39.0	1
Von Hippel-Lindau disease tumor suppressor/Elongin B/Elongin C CHEMBL3301400	Kd	7.16	7.16	69.0	1
von Hippel-Lindau disease tumor suppressor/Elongin-B/Elongin-C/Bromodomain-containing protein 4 CHEMBL4296148	Ki	7.04	6.915	91.0	2
von Hippel-Lindau disease tumor suppressor/Elongin-B/Elongin-C/Bromodomain-containing protein 2 CHEMBL4296149	Ki	6.99	6.825	102.0	2
Bromodomain-containing protein 2 CHEMBL1293289	Kd	6.94	6.555	115.0	4
Bromodomain-containing protein 3 CHEMBL1795186	Kd	6.94	6.9333	115.0	3
Unchecked CHEMBL612545	Ki	6.93	6.875	118.0	2
Caspase-3/Caspase-7 CHEMBL3430905	EC50	6.82	6.82	150.0	1
HL-60 CHEMBL383	EC50	6.66	6.66	218.8	1
Von Hippel-Lindau disease tumor suppressor/Elongin B/Elongin C CHEMBL3301400	Ki	6.55	6.55	282.0	1
CWR22R CHEMBL612657	EC50	6.3	6.3	501.2	1
von Hippel-Lindau disease tumor suppressor/Elongin-B/Elongin-C/Bromodomain-containing protein 4 CHEMBL4296148	IC50	6.21	6.175	623.0	2
von Hippel-Lindau disease tumor suppressor/Elongin-B/Elongin-C/Bromodomain-containing protein 2 CHEMBL4296149	IC50	6.19	6.145	639.0	2
Unchecked CHEMBL612545	IC50	6.18	6.165	660.0	2
Von Hippel-Lindau disease tumor suppressor/Elongin B/Elongin C CHEMBL3301400	IC50	6.05	6.05	882.0	1

Pharmacokinetic Data

Parameter	Value	Units	Species
AUC	160.5	-	Chlorocebus sabaeus
AUC	4522.0	ng.hr.mL-1	Mus musculus
AUC	3770.0	ng.hr.mL-1	Mus musculus
CL	19.7	mL.min-1.kg-1	Mus musculus
Cmax	2070.0	nM	Mus musculus
F	83.0	%	Mus musculus
MRT	0.34	hr	Mus musculus
T1/2	1.04	hr	Mus musculus
T1/2	2.95	hr	Mus musculus
Tmax	0.5	hr	Mus musculus

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
EOL1	IC50	=	1.5	nM	8.82	Antiproliferative activity against human EOL1 cells assessed as inhibition of ce...	36202064
HL-60	IC50	=	1.5	nM	8.82	Antiproliferative activity against human HL-60 cells assessed as inhibition of c...	36202064
von Hippel-Lindau disease tumor suppressor/Elongin-B/Elongin-C/Bromodomain-containing protein 4	Kd	=	9.0	nM	8.05	Induction of interaction of N-terminal His6-tagged recombinant human VHL (54 to ...	28595007
MV4-11	IC50	=	11.3	nM	7.95	Antiproliferative activity against human MV4-11 cells	35763424
Bromodomain-containing protein 4	Kd	=	26.0	nM	7.58	Binding affinity to N-terminal His6-tagged recombinant human Brd4 BD2 expressed ...	28595007
MV4-11	EC50	=	26.92	nM	7.57	Antiproliferative activity against human MV4-11 cells after 48 hrs by CellTiter-...	28595007
von Hippel-Lindau disease tumor suppressor	Kd	=	34.0	nM	7.47	Binding affinity to N-terminal His6-tagged VHL (54 to 213 residues) (unknown ori...	34881891
von Hippel-Lindau disease tumor suppressor/Bromodomain-containing protein 4	Kd	=	39.0	nM	7.41	Binding affinity to N-terminal His6-tagged VHL (54 to 213 residues)/BRD4 BD2 (33...	34881891
MV4-11	EC50	=	50.12	nM	7.3	Antiproliferative activity against human MV4-11 cells assessed as cell growth in...	36202064
von Hippel-Lindau disease tumor suppressor	Kd	=	66.0	nM	7.18	Binding affinity to VHL (unknown origin) assessed as dissociation constant by is...	36202064
Von Hippel-Lindau disease tumor suppressor/Elongin B/Elongin C	Kd	=	69.0	nM	7.16	Binding affinity to N-terminal His6-tagged recombinant human VHL (54 to 213 resi...	28595007
von Hippel-Lindau disease tumor suppressor/Elongin-B/Elongin-C/Bromodomain-containing protein 4	Ki	=	91.0	nM	7.04	Displacement of (2S,4R)-N-(4-bromobenzyl)-4-hydroxy-1-(3,3,3-trifluoropropanoyl)...	34778777
von Hippel-Lindau disease tumor suppressor/Elongin-B/Elongin-C/Bromodomain-containing protein 2	Ki	=	102.0	nM	6.99	Displacement of (2S,4R)-N-(4-bromobenzyl)-4-hydroxy-1-(3,3,3-trifluoropropanoyl)...	34778777
Bromodomain-containing protein 4	Kd	=	115.0	nM	6.94	Binding affinity to BRD4 (unknown origin) assessed as dissociation constant	36202064
Bromodomain-containing protein 3	Kd	=	115.0	nM	6.94	Binding affinity to BRD3 (unknown origin) assessed as dissociation constant	36202064
Bromodomain-containing protein 2	Kd	=	115.0	nM	6.94	Binding affinity to BRD2 (unknown origin) assessed as dissociation constant	36202064
Bromodomain-containing protein 3	Kd	=	115.0	nM	6.94	Binding affinity to BRD3 BD2 domain (unknown origin)	32871345
Unchecked	Ki	=	118.0	nM	6.93	Displacement of (2S,4R)-N-(4-bromobenzyl)-4-hydroxy-1-(3,3,3-trifluoropropanoyl)...	34778777
Bromodomain-containing protein 4	Kd	=	120.0	nM	6.92	Binding affinity to BRD4 BD2 domain (unknown origin)	32871345
Bromodomain-containing protein 3	Kd	=	119.0	nM	6.92	Binding affinity to BRD3 BD1 domain (unknown origin)	32871345

Literature References

PubMed	DOI	Target Context	# Activities
31734632	10.1016/j.neo.2019.10.003	von Hippel-Lindau disease tumor suppressor/Bromodomain-containing protein 4	31
34778777	10.1039/D1MD00215E	Unchecked	28
34652918	10.1021/acs.jmedchem.1c01532	ADMET	10
32858471	10.1016/j.ejmech.2020.112698	von Hippel-Lindau disease tumor suppressor/Bromodomain-containing protein 4	5
28595007	10.1021/acs.jmedchem.6b01912	von Hippel-Lindau disease tumor suppressor/Elongin-B/Elongin-C/Bromodomain-containing protein 4	5
28595007	10.1021/acs.jmedchem.6b01912	Unchecked	4
34778777	10.1039/D1MD00215E	von Hippel-Lindau disease tumor suppressor/Elongin-B/Elongin-C/Bromodomain-containing protein 2	4
34778777	10.1039/D1MD00215E	von Hippel-Lindau disease tumor suppressor/Elongin-B/Elongin-C/Bromodomain-containing protein 4	4
36202064	10.1016/j.bmc.2022.117033	Bromodomain-containing protein 4	3
37902300	10.1021/acs.jmedchem.3c00851	No relevant target	3
38116431	10.1021/acsmedchemlett.3c00314	von Hippel-Lindau disease tumor suppressor/Bromodomain-containing protein 4	3
35763424	10.1021/acs.jmedchem.2c00728	Bromodomain-containing protein 4	3
32353859	10.1038/s41586-020-2286-9	SARS-CoV-2	3
28378579	10.1021/acs.jmedchem.6b01781	No relevant target	3
32353859	10.1038/s41586-020-2286-9	Vero C1008	2
31047748	10.1016/j.bmcl.2019.04.030	von Hippel-Lindau disease tumor suppressor/Bromodomain-containing protein 4	2
32871345	10.1016/j.ejmech.2020.112750	Bromodomain-containing protein 2	2
28595007	10.1021/acs.jmedchem.6b01912	MV4-11	2
28595007	10.1021/acs.jmedchem.6b01912	von Hippel-Lindau disease tumor suppressor/Elongin-B/Elongin-C/Bromodomain-containing protein 3	2
28378579	10.1021/acs.jmedchem.6b01781	von Hippel-Lindau disease tumor suppressor/Bromodomain-containing protein 4	2

Data from ChEMBL 36 via Core Engine