1. Oral Druggable Space beyond the Rule of 5: Insights from Drugs and Clinical Candidates 
Bradley Croy Doak, Bjӧrn Over, Fabrizio Giordanetto, Jan Kihlberg 
Chemistry & Biology 
Volume 21, Issue 9, Pages (September 2014)
DOI: /j.chembiol
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2. Chemistry & Biology 2014 21, 1115-1142DOI: (10. 1016/j. chembiol. 2014
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3. Figure 1
Distribution of Approved Drugs and Clinical Candidates Having MW > 500 Da
(A) Across therapeutic indications and by route of administration.
(B) Across chemical classes and by route of administration.
(C) Year of approval for oral drugs >500 Da from different chemical classes.
(D) Fraction of drugs approved by the FDA having MW >500 Da.
Chemistry & Biology  , DOI: ( /j.chembiol )
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4. Figure 2
Physicochemical Property Space of Drugs and Clinical Candidates Having a MW > 500 Da
Approved oral drugs are in dark blue. Oral clinical candidates are in light blue. Oral clinical candidates for CNS are in yellow, and parenteral drugs and clinical candidates in red. Extended Lipinski’s Ro5 space (solid box, 62% of oral compounds) and limits of oral bRo5 space (dashed box, 93% of compounds) are indicated. The graph limits have been set so as to include all orals in the data set, resulting in an upper MW cut off at 1,600 Da and a number of parenterals fall outside of the limits.
(A) cLogP as a function of MW.
(B) Number of HBDs as a function of MW.
(C) PSA as a function of MW.
(D) NRotBs as a function of MW.
(E) Physicochemical property distribution of chemical classes with mean (95% CI of mean) of MW, cLogP, HBD, number of hydrogen bond donors (HBD) and acceptors (HBA), PSA, NRotB, and Fsp3 carbons.
Chemistry & Biology  , DOI: ( /j.chembiol )
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5. Figure 3
Structures, Calculated Physicochemical Properties, and Data of Relevance for Oral Administration of Erythronolide, Leucomycin, and Rifamycin Antibiotics
Dose, F, and Papp are average adult dosage in mg/day, oral bioavailability in human or preclinical species (p), and Caco-2 AB permeability in 10−6 cm/s where found.
Chemistry & Biology  , DOI: ( /j.chembiol )
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6. Figure 4
Structures, Calculated Physicochemical Properties, and Data of Relevance for Oral Administration of HCV NS3/4A Protease Inhibitors
Dose, F, and Papp are average adult dosage in mg/day, oral bioavailability in human or preclinical species (p), and Caco-2 AB permeability in 10−6 cm/s where found.
Chemistry & Biology  , DOI: ( /j.chembiol )
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7. Figure 5
Structures, Calculated Physicochemical Properties, and Data of Relevance for Oral Administration of Inhibitors of HCV NS5A Inhibitors and HIV Protease Inhibitors and Related Pharmacoenhancers
Dose, F, and Papp are average adult dosage in mg/day, oral bioavailability in human or preclinical species (p), and Caco-2 AB permeability in 10−6 cm/s where found.
Chemistry & Biology  , DOI: ( /j.chembiol )
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8. Figure 6
Structures, Calculated Physicochemical Properties, and Data of Relevance for Oral Administration of Ascomycins, Rapamycins, and Cyclosporins
Dose, F, and Papp are average adult dosage in mg/day, oral bioavailability in human or preclinical species (p), and Caco-2 AB permeability in 10−6 cm/s where found.
Chemistry & Biology  , DOI: ( /j.chembiol )
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9. Figure 7
Structures, Calculated Physicochemical Properties, and Data of Relevance for Oral Administration of Azole Antifungals, Taxanes, Prodrugs and Cardiac Glycosides
Dose, F, and Papp are average adult dosage in mg/day, oral bioavailability in human or preclinical species (p), and Caco-2 AB permeability in 10−6 cm/s where found. The bioavailability is given for the cyclodextrin formulation of Ortataxel and Tesetaxel.
Chemistry & Biology  , DOI: ( /j.chembiol )
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10. Figure 8
Structures, Calculated Physicochemical Properties, and Data of Relevance for Oral Administration of Other Approved and Phase III Compounds in the Oral bRo5 Set
Dose, F, and Papp are average adult dosage in mg/day, oral bioavailability in human or preclinical species (p), and Caco-2 AB permeability in 10−6 cm/s where found.
Chemistry & Biology  , DOI: ( /j.chembiol )
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11. Figure 9
Overview of Chemical Space for Drugs and Clinical Candidates with MW > 500 Da and Trends Found for Orals bRo5
(A) Oral and parenteral categories of drugs and clinical candidates having a MW > 500 Da and extent of “possible to be oral” chemical space.
(B) Major classes of oral drugs and clinical candidates bRo5, common trends that affect oral bioavailability, and origin of leads for the different classes.
Chemistry & Biology  , DOI: ( /j.chembiol )
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