Compound 1602

Identifiers

Common name: JQ1

Canonical SMILES:

Cc1nnc2[C@H](CC(=O)OC(C)(C)C)N=C(c3c(C)c(C)sc3-n12)c1ccc(Cl)cc1

IUPAC name:

tert-butyl 2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetraazatricyclo[8.3.0.0^{2,6}]trideca-2(6),4,7,10,12-pentaen-9-yl]acetate

InChi:

InChI=1S/C23H25ClN4O2S/c1-12-13(2)31-22-19(12)20(15-7-9-16(24)10-8-15)25-17(11-18(29)30-23(4,5)6)21-27-26-14(3)28(21)22/h7-10,17H,11H2,1-6H3/t17-/m0/s1

InChiKey:
```
DNVXATUJJDPFDM-KRWDZBQOSA-N
```

External links

46907787

CHEMBL1957266

JQ1

External search

Bibliography (3)

Publication	Name
Filippakopoulos P, Qi J, Picaud S, Shen Y, Smith WB, Fedorov O, Morse EM, Keates T, Hickman TT, Felletar I, Philpott M, Munro S, McKeown MR, Wang Y, Christie AL, West N, Cameron MJ, Schwartz B, Heightman TD, La Thangue N, French CA, Wiest O, Kung AL, Knapp S, Bradner JE. . Selective inhibition of BET bromodomains. Nature.	(+)-JQ1
Matzuk MM, McKeown MR, Filippakopoulos P, Li Q, Ma L, Agno JE, Lemieux ME, Picaud S, Yu RN, Qi J, Knapp S, Bradner JE. . Small-molecule inhibition of BRDT for male contraception. Cell.	(+)-JQ1
Ouyang Liang, Zhang Lan, Liu Jie, Fu Leilei, Yao Dahong, Zhao Yuqian, Zhang Shouyue, Wang Guan, He Gu, Liu Bo. . Discovery of a Small-Molecule Bromodomain-Containing Protein 4 (BRD4) Inhibitor That Induces AMP-Activated Protein Kinase-Modulated Autophagy-Associated Cell Death in Breast Cancer Journal of Medicinal Chemistry.	1

Pharmacological data

Biochemical tests	Cellular tests	PK tests	Cytotoxicity tests
12	3	0	0

Targets

PPI family	Best activity	Diseases	MMoA
Bromodomain / Histone	8.40	cancer , breast cancer	Inhibition

Physicochemical filters

Descriptor	Lipinski's RO5	Veber	Pfizer's 3/75
MW	≤ 500 g/mol	-	-
AlogP	≤ 5	-	≤ 3
HBA	≤ 10	-	-
HBD	≤ 5	-	-
(HBA + HBD)	-	≤ 12	-
TPSA	-	≤ 140 Å²	≥ 75 Å²
RB	-	≤ 10	-

	Descriptor	Lipinski's RO5	Veber	Pfizer's 3/75
Compliance
MW	456.14 g/mol
HBA	6
HBD	0
HBA + HBD	6
AlogP	5.26
TPSA	69.37
RB	5

Radar chart

Short name	Threshold
MW	≤ 500 g/mol
AlogP	≤ 5
HBD	≤ 5
HBA	≤ 10
TPSA	≤ 140 Å²
RB	≤ 10
ArRing	≤ 4
Fsp3	≥ 0.4
R/S	≥ 1

PCA : iPPI-DB chemical space

PCA : Correlation circle

Efficiencies: iPPI-DB biplot LE versus LLE

Summary

Bibliographic ressources	Biochemical tests	Cellular tests	PK tests	Cytotoxicity tests
3	12	3	0	0

Pharmacological data

Bibliography	Name	Target	Competition	Assay type	Assay name	Cell line	Activity type	Activity
20871596	(+)-JQ1	BRD4 O60885		Biochemical assay	Isothermal Titration Calorimetry		pKd (dissociation constant, -log10)	7.30
20871596	(+)-JQ1	BRD4 O60885		Biochemical assay	alphascreen		pIC50 (half maximal inhibitory concentration, -log10)	7.11
20871596	(+)-JQ1	BRD4 O60885		Cellular assay	cellular viability		pIC50 (half maximal inhibitory concentration, -log10)	8.40
22901802	(+)-JQ1	BRDT Q58F21		Biochemical assay	alphascreen		pIC50 (half maximal inhibitory concentration, -log10)	7.96
22901802	(+)-JQ1	BRDT Q58F21		Biochemical assay	Isothermal Titration Calorimetry		pKd (dissociation constant, -log10)	6.72
10.1021/acs.jmedchem.7b00275	1	BRD4 O60885	H4 P62805	Biochemical assay	Time-Resolved FRET BRDT(1)		pIC50 (half maximal inhibitory concentration, -log10)	6.77
10.1021/acs.jmedchem.7b00275	1	BRD4 O60885	H4 P62805	Biochemical assay	Time-Resolved FRET BRD4(2)		pIC50 (half maximal inhibitory concentration, -log10)	7.59
10.1021/acs.jmedchem.7b00275	1	BRD4 O60885	H4 P62805	Biochemical assay	Time-Resolved FRET BRD4(1)		pIC50 (half maximal inhibitory concentration, -log10)	7.12
10.1021/acs.jmedchem.7b00275	1	BRD4 O60885	H4 P62805	Biochemical assay	Time-Resolved FRET BRD3(2)		pIC50 (half maximal inhibitory concentration, -log10)	7.41
10.1021/acs.jmedchem.7b00275	1	BRD4 O60885	H4 P62805	Biochemical assay	Time-Resolved FRET BRD3(1)		pIC50 (half maximal inhibitory concentration, -log10)	7.23
10.1021/acs.jmedchem.7b00275	1	BRD4 O60885	H4 P62805	Biochemical assay	Time-Resolved FRET BRD2(2)		pIC50 (half maximal inhibitory concentration, -log10)	7.77
10.1021/acs.jmedchem.7b00275	1	BRD4 O60885	H4 P62805	Biochemical assay	Time-Resolved FRET BRD2(1)		pIC50 (half maximal inhibitory concentration, -log10)	6.84
10.1021/acs.jmedchem.7b00275	1	BRD4 O60885	H4 P62805	Cellular assay	Anti-proliferative MDA-MB-231	MDA-MB-231 breast	pIC50 (half maximal inhibitory concentration, -log10)	4.48
10.1021/acs.jmedchem.7b00275	1	BRD4 O60885	H4 P62805	Cellular assay	Anti-proliferative MCF-7	MCF7 mammary carcinoma cells	pIC50 (half maximal inhibitory concentration, -log10)	4.54
10.1021/acs.jmedchem.7b00275	1	BRD4 O60885	H4 P62805	Biochemical assay	alphascreen BRD4		pIC50 (half maximal inhibitory concentration, -log10)	7.14

Ta	Name	Drugbank ID
0.8571	RO-6870810	DB15151
0.8413	Birabresib	DB15189
0.7109	Etizolam	DB09166
0.6442	Brotizolam	DB09017
0.4848	Clonazolam	DB14716
0.4841	Alprazolam	DB00404
0.4806	Triazolam	DB00897
0.4695	Adinazolam	DB00546
0.4643	Estazolam	DB01215
0.4639	Nitrazolam	DB14717
0.4532	Pyrazolam	DB14718
0.4348	Remimazolam	DB12404
0.3932	Clotiazepam	DB01559
0.3833	Midazolam	DB00683
0.3758	Bentazepam	DB14719