Contrasting effect of the latency-reversing agents bryostatin-1 and JQ1 on astrocyte-mediated neuroinflammation and brain neutrophil invasion

Table 1 Activity, CNS penetrance, and concentrations of LRA and positive controls

Compounds (activity)	CNS penetrance [4]	Concentrations used in our study	HIV-1 reactivating concentrations in vitro	Plasmatic concentrations^a
Bryostatin-1 (PKC modulator)	++	25 nM	0.25–100 nM [29]	0.05 nM^b [28]
JQ1 (BRDi)	++	0.5 μM	0.5 μM [53]	ND
SAHA (HDACi)	+++	1 μM	0.1–10 μM [53,54,55]	1 μM [56, 57]
HMBA (Tat mimetic)	++	1 mM	1–5 mM [58, 59]	0.0019 mM [60]
Disulfiram (Akt signaller)	+++	1 μM	0.1–10 μM [53, 61, 62]	0.2 μM [63] 2 μM [64]
Bix-01294 (HMTi)	ND	1 μM	1–10 μM [65]	ND
Positive controls: poly(I:C) Pam3Csk4		30 μg/mL 10 μg/mL

PKC protein kinase C, BRDi bromodomain inhibitor, SAHA suberoylanilide hydroxamide acid, HDACi histone deacetylase inhibitor, HMBA hexamethylene bisacetamide, HMTi histone methyltransferase inhibitor, TLR Toll-like receptor, poly(I:C) polyinosinic/polycytidylic acid, ++/+++ good/very good penetration, ND not determined
^aMaximum in vivo plasma concentration in humans
^bNo HIV-1 reactivation at this low in vivo plasma concentration in humans

ISSN: 1742-2094