Journal: Fluids and Barriers of the CNS

Article Title: ATP-binding cassette transporter inhibitor potency and substrate drug affinity are critical determinants of successful drug delivery enhancement to the brain

doi: 10.1186/s12987-024-00562-4

Figure Lengend Snippet: Brain penetration (B/P-ratio) of each drug as a function of inhibitor plasma level. The drugs are classified as: (I) Abcb1 only substrates, (II) Abcb1 and weak Abcg2 substrates and (III) Abcb1 and strong Abcg2 substrates, as shown below. The inhibitor concentration vs. brain-to-plasma ratios curves were fitted using the [Agonist] vs. response –Variable slope (four parameters) nonlinear fit in Graphpad Prism 10.1.2. The dashed lines indicate the 90% CI around the curves

Article Snippet: The inhibitor concentration vs. intracellular drug level concentrations were fitted using the [Agonist] vs. response –Variable slope (four parameters) nonlinear fit in Graphpad Prism 10.1.2.

Techniques: Concentration Assay

Journal: Fluids and Barriers of the CNS

Article Title: ATP-binding cassette transporter inhibitor potency and substrate drug affinity are critical determinants of successful drug delivery enhancement to the brain

doi: 10.1186/s12987-024-00562-4

Figure Lengend Snippet: Potency of elacridar and tariquidar to inhibit Abcg2 and Abcb1a/b. The drugs are classified as: (I) Abcb1 only substrates, (II) Abcb1 and weak Abcg2 substrates and (III) Abcb1 and strong Abcg2 substrates, as shown below. The accumulation of the substrates in Abcb1 KO mice (blue bars), Abcg2 KO mice (green bars) and WT mice (black bars). The color-filled bars show the maximum gain with elacridar or tariquidar. The red dotted line (100%) designates the accumulation of drugs in Abcg2;Abcb1a/b KO mice. The inhibitor concentration vs. brain-to-plasma ratio were fitted using the [Agonist] vs. response –Variable slope (four parameters) nonlinear fit in Graphpad Prism 10.1.2

Article Snippet: The inhibitor concentration vs. intracellular drug level concentrations were fitted using the [Agonist] vs. response –Variable slope (four parameters) nonlinear fit in Graphpad Prism 10.1.2.

Techniques: Concentration Assay

Journal: Fluids and Barriers of the CNS

Article Title: ATP-binding cassette transporter inhibitor potency and substrate drug affinity are critical determinants of successful drug delivery enhancement to the brain

doi: 10.1186/s12987-024-00562-4

Figure Lengend Snippet: Plasma protein binding of elacridar and tariquidar. Mouse plasma (MP) and human plasma (HP), each diluted 30% (v/v) in MEM and spiked with 1000 nM elacridar and tariquidar was added to the sample chamber (s), while the buffer compartment (b) was filled with 30% (v/v) diluted human or mouse plasma, respectively, containing 1000 nM of elacridar-d9. Depicted is the recovery after 24 h incubation at 37 °C. As an example: From MP(s) into HP(b) describes the drug concentration recovered in human plasma (HP) in the buffer (b) chamber (receiver) coming from mouse plasma (MP) spiked with drug in the sample (s) chamber (donor). Students t-test (Graphpad Prism 10.1.2) Created with BioRender.com

Article Snippet: The inhibitor concentration vs. intracellular drug level concentrations were fitted using the [Agonist] vs. response –Variable slope (four parameters) nonlinear fit in Graphpad Prism 10.1.2.

Techniques: Protein Binding, Incubation, Concentration Assay

Journal: Fluids and Barriers of the CNS

Article Title: ATP-binding cassette transporter inhibitor potency and substrate drug affinity are critical determinants of successful drug delivery enhancement to the brain

doi: 10.1186/s12987-024-00562-4

Figure Lengend Snippet: Brain penetration (B/P-ratio) of each drug as a function of inhibitor plasma level. The drugs are classified as: (I) Abcb1 only substrates, (II) Abcb1 and weak Abcg2 substrates and (III) Abcb1 and strong Abcg2 substrates, as shown below. The inhibitor concentration vs. brain-to-plasma ratios curves were fitted using the [Agonist] vs. response –Variable slope (four parameters) nonlinear fit in Graphpad Prism 10.1.2. The dashed lines indicate the 90% CI around the curves

Article Snippet: The inhibitor concentration vs. brain-to-plasma ratios curves were fitted using the [Agonist] vs. response –Variable slope (four parameters) nonlinear fit in Graphpad Prism 10.1.2.

Techniques: Clinical Proteomics, Concentration Assay

Journal: Fluids and Barriers of the CNS

Article Title: ATP-binding cassette transporter inhibitor potency and substrate drug affinity are critical determinants of successful drug delivery enhancement to the brain

doi: 10.1186/s12987-024-00562-4

Figure Lengend Snippet: Potency of elacridar and tariquidar to inhibit Abcg2 and Abcb1a/b. The drugs are classified as: (I) Abcb1 only substrates, (II) Abcb1 and weak Abcg2 substrates and (III) Abcb1 and strong Abcg2 substrates, as shown below. The accumulation of the substrates in Abcb1 KO mice (blue bars), Abcg2 KO mice (green bars) and WT mice (black bars). The color-filled bars show the maximum gain with elacridar or tariquidar. The red dotted line (100%) designates the accumulation of drugs in Abcg2;Abcb1a/b KO mice. The inhibitor concentration vs. brain-to-plasma ratio were fitted using the [Agonist] vs. response –Variable slope (four parameters) nonlinear fit in Graphpad Prism 10.1.2

Article Snippet: The inhibitor concentration vs. brain-to-plasma ratios curves were fitted using the [Agonist] vs. response –Variable slope (four parameters) nonlinear fit in Graphpad Prism 10.1.2.

Techniques: Concentration Assay, Clinical Proteomics