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Chemical Probes Portal JQ1.pdf
JQ1

Reagent Authentication Certificate:

Protein target name:
BRD2, BRD3, BRD4, BRDTMechanism of action:
AntagonistRecommended Concentration for use in cells:
10 nM - 1 uM
Probe Availability
Probe Information
In vitro validation
Potency:
KDBRD4 (N): 49.0 nM
Potency assay:
KD: BRD2 128 nM, BRD3 (N) 59.1 nM, BRD3 (C) 82.0 nM, BRD4 (C) 90.1 nM; BRDT (N): 190.1 nM, ITC assay
IC50: BRD2 17.7 nM, BRD4 (N) 76.9 nM, BRD4 (C) 32.6 nM, alpha screen
PDB ID for probe-target interaction (3D structure):
2OSS, 3MXF, 3ONIOff target protein and potency:
ATAD2: 0.18CREBBP: 1.04EP300: 0.07KIAA1240: 0.05PB1/3: 0.79SMARCA2: 0.93SMARCA4: 0.15TAF1/2: 0.28TAF1/3: 0.50TAF1L/2: 0.04Potency assay (off target):
Differential scanning fluorimetry; for comparison BRD2/1: 6.47, BRD2/2: 7.97, BRD3/1: 8.27, BRD3/2: 8.39, BRD4/1: 9.35, BRD4/2: 7.44, BRDT/1: 3.93.
No activity was detected against: ASH1L, BAZ2B, BRD1, BRD9, BRPF1, CECR2, FALZ, GCN5L2, LOC93349, PB1/1, PB1/2, PB1/5, PB1/6, PCAF, PHIP/2, SP140, TAF1L/3, TIF1, WDR9
Probe Selectivity in Vitro:
In ExpressProfile, negligible activity was detected: H2 [cimetindine]: -27, Neurokinin NK3 [SB 222200]: -23, Somatostatin SST [somatostatin-14]: -22
Benzodiazepine [diazepam]: -20, Prostanoid TP (TXA2/PGH2)[U 44069]: -19, Serotonin 5-HT transporter [imipramine]: -19, Serotonin 5-HT1A [8-OH-DPAT]: : -14, Muscarinic M1 [pirenzepine]: -14, GABA [GABA]: -12, Serotonin 5-HT7 [serotonin]: -12, Norepinephrine transporter [protriptyline]: -10, Adenosine A1 [DPCPX]: -10, Adenosine A2A [NECA]: -9, VPAC1 [VIP]: -9, Dopamine transporter [BTCP]: -7, Alpha-2 Adrenergic (nonselective) [yohimbine]:-7, Serotonin 5-HT5a [serotonin]: -7, Opioid Delta 2 (DOP) [DPDPE]: -6, Serotonin 5-HT3 [MDL 7222]: -6, Chemokine CXCR2 (IL-8B) [IL-8]: -5
Alpha-1 Adrenergic (nonselective) [prazosin]: -5, Histamine H1 [pyrilamine]: -5, Vasopressin V1a [[d(CH2)51Tyr(Me)2]-AVP]: -5, Ca2+ channel [D 600]: -5
Chemokine CCR1 [MIP-1alpha]: -4, Opioid Mu (MOP) [DAMGO]: -4, K+ (KV) channel [alpha-dendrotoxin]: -4, Serotonin 5-HT1B [serotonin]: -4,, Muscarinic M3 [4-DAMP]: -4, Neurotensin NTS1 (NT1) [neurotensin]: -4, Bradykinin B2 [NPC 567]: -3, Opioid-like NOP (ORL1) [nociception]: -2, Dopamine D1 [SCH 23390]: -2, Dopamine D2S [(+)-butaclamol]:-2, Neuropeptide Y1 [NPY]: -2, Serotonin 5-HT2B [DOI]: -2, Angiotensin-II AT1 [saralasin]: 0, Cannabinoid CB1 [CP 55940]: 0, Melanocortin MC4 [NDP-alpha-MSH]: 0, Beta-1 Adrenergic [atenolol]: +1, Muscarinic M2 [methoctramine]: +2, Serotonin 5-HT6 [serotonin]: +2, Cl- channel (GABA gated) [picrotoxinin]: +3, K+ Channel SKCa [apamin]: +3, Opioid Kappa (KOP) [U 50488]: +3
Beta-2 Adrenergic [ICI 118551]: +4, Galanin GAL2 [galanin]: +5, Cholecystokinin CCK1 (CCKA) [CCK-8s]: +9, Neuropeptide Y2 [NPY]: +10, Endothelin ETA [endothelin-1]: +16, Na+ channel [veratridine]: +18, Serotonin 5-HT2A [ketanserin]: +24, Melatonin MT1( ML1A) [melatonin]: +29, Neurokinin NK2 [[Nleu10]-NKA (4010)]: +56, Adenosine A3 [IB-MECA]: +61
In cell validation
Potency assay (cells):
Human osteosarcoma cells (U2OS) transfected with GFP–BRD4 show a time-dependent recovery of fluorescence intensity in Fluorescence recovery after photobleaching (FRAP) assay. In the presence of JQ1 (500 nM), the observed recovery is immediate, indicating displaced and freely diffusing nuclear BRD4. Cellular FRAP studies confirmed that the effects on the mobile fraction of BRD4 are limited to the biochemically active (1)-JQ1 stereoisomer.Target engagement assay (cells):
Indirect: FRAP assayToxicity
Cytoxicity assay:
YesNotes on cytotoxicity:
At 500 nM, JQ1 leads to on target, BRD4-dependent apoptosis.In vivo validation
Organism:
MouseDose:
50 mg/kgRoute of delivery:
OralOther route of delivery:
IntravenousPlasma half life:
0.897 hr (IV), 1.39 hr (oral)Systemic clearance:
2.35 L/hr/kg (IV)Cmax:
1,180 ng/mL (oral)Tmax:
0.250 hr (oral)Organ (O):
xenograftTarget engagement assay:
Indirect: effacement of NUT nuclear speckles, consistent with competitive binding to nuclear chromatin