Compound 1603

Identifiers

Common name: I-BET

Canonical SMILES:

CCNC(=O)C[C@@H]1N=C(c2ccc(Cl)cc2)c2cc(OC)ccc2-n2c(C)nnc12

IUPAC name:

2-[(7S)-9-(4-chlorophenyl)-12-methoxy-3-methyl-2,4,5,8-tetraazatricyclo[8.4.0.0^{2,6}]tetradeca-1(10),3,5,8,11,13-hexaen-7-yl]-N-ethylacetamide

InChi:

InChI=1S/C22H22ClN5O2/c1-4-24-20(29)12-18-22-27-26-13(2)28(22)19-10-9-16(30-3)11-17(19)21(25-18)14-5-7-15(23)8-6-14/h5-11,18H,4,12H2,1-3H3,(H,24,29)/t18-/m0/s1

InChiKey:
```
AAAQFGUYHFJNHI-SFHVURJKSA-N
```

External links

46943432

CHEMBL1232461

EAM

External search

Bibliography (4)

Publication	Name
Dawson MA, Prinjha RK, Dittmann A, Giotopoulos G, Bantscheff M, Chan WI, Robson SC, Chung CW, Hopf C, Savitski MM, Huthmacher C, Gudgin E, Lugo D, Beinke S, Chapman TD, Roberts EJ, Soden PE, Auger KR, Mirguet O, Doehner K, Delwel R, Burnett AK, Jeffrey P, Drewes G, Lee K, Huntly BJ, Kouzarides T. . Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. Nature.	I-BET762
Nicodeme E, Jeffrey KL, Schaefer U, Beinke S, Dewell S, Chung CW, Chandwani R, Marazzi I, Wilson P, Coste H, White J, Kirilovsky J, Rice CM, Lora JM, Prinjha RK, Lee K, Tarakhovsky A. . Suppression of inflammation by a synthetic histone mimic. Nature.	I-BET
Chung Chun-wa, Coste Hervé, White Julia H., Mirguet Olivier, Wilde Jonathan, Gosmini Romain L., Delves Chris, Magny Sylvie M., Woodward Robert, Hughes Stephen A., Boursier Eric V., Flynn Helen, Bouillot Anne M., Bamborough Paul, Brusq Jean-Marie G., Gellibert Françoise J., Jones Emma J., Riou Alizon M., Homes Paul, Martin Sandrine L., Uings Iain J., Toum Jérôme, Clément Catherine A., Boullay Anne-Bénédicte, Grimley Rachel L., Blandel Florence M., Prinjha Rab K., Lee Kevin, Kirilovsky Jorge, Nicodeme Edwige. . Discovery and Characterization of Small Molecule Inhibitors of the BET Family Bromodomains Journal of Medicinal Chemistry.	Compound 2
Baud Matthias G. J., Lin-Shiao Enrique, Zengerle Michael, Tallant Cynthia, Ciulli Alessio. . New Synthetic Routes to Triazolo-benzodiazepine Analogues: Expanding the Scope of the Bump-and-Hole Approach for Selective Bromo and Extra-Terminal (BET) Bromodomain Inhibition Journal of Medicinal Chemistry.	Compound 1

Pharmacological data

Biochemical tests	Cellular tests	PK tests	Cytotoxicity tests
14	4	0	0

Targets

PPI family	Best activity	Diseases	MMoA
Bromodomain / Histone	7.49	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	423.15 g/mol
HBA	7
HBD	1
HBA + HBD	8
AlogP	2.57
TPSA	81.40
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
4	14	4	0	0

Pharmacological data

Bibliography	Name	Target	Competition	Assay type	Assay name	Cell line	Activity type	Activity
21068722	I-BET	BRD4 O60885		Biochemical assay	Isothermal Titration Calorimetry		pKd (dissociation constant, -log10)	7.26
21068722	I-BET	BRD2 P25440		Biochemical assay	FRET		pIC50 (half maximal inhibitory concentration, -log10)	7.49
21068722	I-BET	BRD3 Q15059		Biochemical assay	FRET		pIC50 (half maximal inhibitory concentration, -log10)	7.37
21964340	I-BET762	BRD2 P25440		Biochemical assay	Fluorescence Polarization		pIC50 (half maximal inhibitory concentration, -log10)	6.10
21964340	I-BET762	BRD3 Q15059		Biochemical assay	Fluorescence Polarization		pIC50 (half maximal inhibitory concentration, -log10)	6.40
21964340	I-BET762	BRD4 O60885		Biochemical assay	Fluorescence Polarization		pIC50 (half maximal inhibitory concentration, -log10)	6.20
21964340	I-BET762	BRD3 Q15059		Biochemical assay	Surface Plasmon Resonance		pKd (dissociation constant, -log10)	6.70
21964340	I-BET762	BRD4 O60885		Biochemical assay	Surface Plasmon Resonance		pKd (dissociation constant, -log10)	6.49
21964340	I-BET762	BRD4 O60885		Cellular assay	LPS-stimulated IL6 production	PBMC	pIC50 (half maximal inhibitory concentration, -log10)	6.70
21964340	I-BET762	BRD4 O60885		Cellular assay	LPS-stimulated IL6 production	Human Whole Blood	pIC50 (half maximal inhibitory concentration, -log10)	6.20
21964340	I-BET762	BRD4 O60885		Cellular assay	LPS-stimulated IL6 production	Rat Whole Blood	pIC50 (half maximal inhibitory concentration, -log10)	5.80
21068722	I-BET	BRD3 Q15059		Biochemical assay	Isothermal Titration Calorimetry		pKd (dissociation constant, -log10)	7.30
21068722	I-BET	BRD2 P25440		Biochemical assay	Isothermal Titration Calorimetry		pKd (dissociation constant, -log10)	7.21
21068722	I-BET	BRD4 O60885		Biochemical assay	FRET		pIC50 (half maximal inhibitory concentration, -log10)	7.44
10.1021/jm200108t	Compound 2	BRD2 P25440	H4 P02309	Cellular assay	Induction of ApoA1 expression by Luciferase reporter assay	HepG2 cells	pEC50 (half maximal effective concentration, -log10)	6.15
10.1021/jm200108t	Compound 2	BRD2 P25440	H4 P02309	Biochemical assay	FRET BRD2		pIC50 (half maximal inhibitory concentration, -log10)	7.49
10.1021/jm200108t	Compound 2	BRD2 P25440	H4 P02309	Biochemical assay	FRET BRD3		pIC50 (half maximal inhibitory concentration, -log10)	7.37
10.1021/jm200108t	Compound 2	BRD2 P25440	H4 P02309	Biochemical assay	FRET BRD4		pIC50 (half maximal inhibitory concentration, -log10)	7.44

Ta	Name	Drugbank ID
0.6618	Birabresib	DB15189
0.6618	RO-6870810	DB15151
0.6039	Alprazolam	DB00404
0.5962	Triazolam	DB00897
0.5954	Adinazolam	DB00546
0.5837	Clonazolam	DB14716
0.5797	Estazolam	DB01215
0.5450	Nitrazolam	DB14717
0.5310	Pyrazolam	DB14718
0.4832	Etizolam	DB09166
0.4758	Brotizolam	DB09017
0.4431	Midazolam	DB00683
0.4387	Remimazolam	DB12404
0.4302	Balovaptan	DB14823
0.4024	Tepoxalin	DB11466