AZD8309: CXCR2 inhibitor [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]
| ID Source | ID |
|---|---|
| PubMed CID | 12073810 |
| CHEMBL ID | 446458 |
| SCHEMBL ID | 841899 |
| MeSH ID | M0574772 |
| Synonym |
|---|
| CHEMBL446458 , |
| bdbm50371784 |
| SCHEMBL841899 |
| SRHSMXLXWORYJK-SSDOTTSWSA-N |
| 5-[[(2,3-difluorophenyl)methyl]thio]-7-[[(1r)-2-hydroxy-1-methylethyl]amino]thiazolo[4,5-d]pyrimidin-2-(3h)-one |
| azd8309 |
| 8PD78CVU5V |
| thiazolo[4,5-d]pyrimidin-2(3h)-one, 5-[[(2,3-difluorophenyl)methyl]thio]-7-[[(1r)-2-hydroxy-1-methylethyl]amino]- |
| azd-8309 |
| 5-[[(2,3-difluorophenyl)methyl]thio]-7-[[(1r)-2-hydroxy-1-methylethyl]amino]thiazolo[4,5-d]pyrimidin-2(3h)-one |
| (r)-5-((2,3-difluorobenzyl)thio)-7-((1-hydroxypropan-2-yl)amino)thiazolo[4,5-d]pyrimidin-2(3h)-one |
| 333742-48-6 |
| HY-119259 |
| CS-0077438 |
| 5-[(2,3-difluorophenyl)methylsulfanyl]-7-[[(2r)-1-hydroxypropan-2-yl]amino]-3h-[1,3]thiazolo[4,5-d]pyrimidin-2-one |
| AKOS040746606 |
Treatment with AZD8309 showed a mean 77% reduction in total sputum cells (p < 0.001) and 79% Reduction in neutrophils (p = 0.05) compared with placebo after LPS challenge.
| Excerpt | Reference | Relevance |
|---|---|---|
| "Treatment with AZD8309 showed a mean 77% reduction in total sputum cells (p < 0.001) and 79% reduction in sputum neutrophils (p < 0.05) compared with placebo after LPS challenge. " | ( Inhibition of LPS-induced airway neutrophilic inflammation in healthy volunteers with an oral CXCR2 antagonist. Barnes, PJ; Leaker, BR; O'Connor, B, 2013) | 0.74 |
| "Treatment with AZD8309 reduced the leucocyte count to 48% of placebo 6 h after the LPS challenge." | ( Airway inflammation evaluated in a human nasal lipopolysaccharide challenge model by investigating the effect of a CXCR2 inhibitor. Cardell, LO; Ekman, AK; Jansson, L; Virtala, R; Westin, U, 2012) | 0.72 |
| Excerpt | Reference | Relevance |
|---|---|---|
| " We have investigated the effect of AZD8309, a potent and orally bioavailable antagonist of the chemokine receptor CXCR2, which has been proposed to regulate the transmigration of neutrophils." | ( Effect of oral administration of AZD8309, a CXCR2 antagonist, on the severity of experimental pancreatitis. D'Haese, J; Günther, A; Hansen, MB; Kärrman Mårdh, C; Lerch, MM; Mahajan, UM; Malla, SR; Mayerle, J; Sendler, M; Weiss, FU, ) | 0.69 |
AZD8309 (300 mg) or placebo was dosed twice daily orally for 3 days prior to challenge with inhaled LPS. induced sputum was collected 6 h later.
| Excerpt | Relevance | Reference |
|---|---|---|
| " AZD8309 or placebo was dosed for 3 days." | ( Airway inflammation evaluated in a human nasal lipopolysaccharide challenge model by investigating the effect of a CXCR2 inhibitor. Cardell, LO; Ekman, AK; Jansson, L; Virtala, R; Westin, U, 2012) | 1.29 |
| " AZD8309 (300 mg) or placebo was dosed twice daily orally for 3 days prior to challenge with inhaled LPS and induced sputum was collected 6 h later." | ( Inhibition of LPS-induced airway neutrophilic inflammation in healthy volunteers with an oral CXCR2 antagonist. Barnes, PJ; Leaker, BR; O'Connor, B, 2013) | 1.3 |
| Protein | Taxonomy | Measurement | Average | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| C-X-C chemokine receptor type 2 | Homo sapiens (human) | IC50 (µMol) | 0.0010 | 0.0000 | 0.3029 | 6.0130 | AID1193191; AID316041 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
| Protein | Taxonomy | Measurement | Average | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| C-X-C chemokine receptor type 2 | Homo sapiens (human) | Kd | 0.0013 | 0.0013 | 0.0013 | 0.0013 | AID1193196 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
| Protein | Taxonomy | Measurement | Average | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| C-C chemokine receptor type 2 | Homo sapiens (human) | pA2 | 0.0060 | 0.0060 | 0.0060 | 0.0060 | AID316047 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
| Assay ID | Title | Year | Journal | Article |
|---|---|---|---|---|
| AID316046 | Distribution coefficient, log D of the compound | 2008 | Bioorganic & medicinal chemistry letters, Jan-15, Volume: 18, Issue:2 | Evaluation of a series of bicyclic CXCR2 antagonists. |
| AID1193201 | Clearance in iv dosed rat | 2015 | Bioorganic & medicinal chemistry letters, Apr-01, Volume: 25, Issue:7 | Discovery and evaluation of a novel monocyclic series of CXCR2 antagonists. |
| AID1193196 | Antagonist activity at CXCR2 receptor in HEK293 cells assessed as mobilization of intracellular calcium by FLIPR analysis | 2015 | Bioorganic & medicinal chemistry letters, Apr-01, Volume: 25, Issue:7 | Discovery and evaluation of a novel monocyclic series of CXCR2 antagonists. |
| AID1193194 | Fraction unbound in human plasma by equilibrium dialysis method | 2015 | Bioorganic & medicinal chemistry letters, Apr-01, Volume: 25, Issue:7 | Discovery and evaluation of a novel monocyclic series of CXCR2 antagonists. |
| AID1193204 | Dose normalized AUC in po dosed rat | 2015 | Bioorganic & medicinal chemistry letters, Apr-01, Volume: 25, Issue:7 | Discovery and evaluation of a novel monocyclic series of CXCR2 antagonists. |
| AID316042 | Oral bioavailability in rat | 2008 | Bioorganic & medicinal chemistry letters, Jan-15, Volume: 18, Issue:2 | Evaluation of a series of bicyclic CXCR2 antagonists. |
| AID1193195 | Lipophilicity, log D of the compound by shake flask technique | 2015 | Bioorganic & medicinal chemistry letters, Apr-01, Volume: 25, Issue:7 | Discovery and evaluation of a novel monocyclic series of CXCR2 antagonists. |
| AID1193193 | Dissociation constant, pKa of the compound | 2015 | Bioorganic & medicinal chemistry letters, Apr-01, Volume: 25, Issue:7 | Discovery and evaluation of a novel monocyclic series of CXCR2 antagonists. |
| AID316043 | Clearance in rat | 2008 | Bioorganic & medicinal chemistry letters, Jan-15, Volume: 18, Issue:2 | Evaluation of a series of bicyclic CXCR2 antagonists. |
| AID1193197 | Intrinsic clearance in human hepatocytes assessed per 10'6 cells | 2015 | Bioorganic & medicinal chemistry letters, Apr-01, Volume: 25, Issue:7 | Discovery and evaluation of a novel monocyclic series of CXCR2 antagonists. |
| AID316044 | Protein binding as % unbound in human plasma | 2008 | Bioorganic & medicinal chemistry letters, Jan-15, Volume: 18, Issue:2 | Evaluation of a series of bicyclic CXCR2 antagonists. |
| AID316047 | Antagonist activity at human CCR2 in THP1 cells by FLIPR | 2008 | Bioorganic & medicinal chemistry letters, Jan-15, Volume: 18, Issue:2 | Evaluation of a series of bicyclic CXCR2 antagonists. |
| AID316041 | Displacement of [125I]IL8 from human recombinant CXCR2 expressed in HEK293 cells by SPA assay | 2008 | Bioorganic & medicinal chemistry letters, Jan-15, Volume: 18, Issue:2 | Evaluation of a series of bicyclic CXCR2 antagonists. |
| AID1193192 | Solubility of the compound in 0.1 M phosphate buffer at pH 7.4 after overnight incubation by HPLC analysis | 2015 | Bioorganic & medicinal chemistry letters, Apr-01, Volume: 25, Issue:7 | Discovery and evaluation of a novel monocyclic series of CXCR2 antagonists. |
| AID1193191 | Displacement of [125I]IL-8 from human recombinant CXCR2 receptor expressed in HEK293 cells by scintillation counting analysis | 2015 | Bioorganic & medicinal chemistry letters, Apr-01, Volume: 25, Issue:7 | Discovery and evaluation of a novel monocyclic series of CXCR2 antagonists. |
| AID1193202 | Volume of distribution at steady state in iv dosed rat | 2015 | Bioorganic & medicinal chemistry letters, Apr-01, Volume: 25, Issue:7 | Discovery and evaluation of a novel monocyclic series of CXCR2 antagonists. |
| AID316045 | Dissociation constant, pKa of the compound | 2008 | Bioorganic & medicinal chemistry letters, Jan-15, Volume: 18, Issue:2 | Evaluation of a series of bicyclic CXCR2 antagonists. |
| AID1193200 | Fraction of the dose absorbed in iv dosed rat | 2015 | Bioorganic & medicinal chemistry letters, Apr-01, Volume: 25, Issue:7 | Discovery and evaluation of a novel monocyclic series of CXCR2 antagonists. |
| AID1193199 | Bioavailability in iv dosed rat | 2015 | Bioorganic & medicinal chemistry letters, Apr-01, Volume: 25, Issue:7 | Discovery and evaluation of a novel monocyclic series of CXCR2 antagonists. |
| AID1193203 | Half life in iv dosed rat | 2015 | Bioorganic & medicinal chemistry letters, Apr-01, Volume: 25, Issue:7 | Discovery and evaluation of a novel monocyclic series of CXCR2 antagonists. |
| [information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||||
| Timeframe | Studies, This Drug (%) | All Drugs % |
|---|---|---|
| pre-1990 | 0 (0.00) | 18.7374 |
| 1990's | 0 (0.00) | 18.2507 |
| 2000's | 1 (25.00) | 29.6817 |
| 2010's | 3 (75.00) | 24.3611 |
| 2020's | 0 (0.00) | 2.80 |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||
| Publication Type | This drug (%) | All Drugs (%) |
|---|---|---|
| Trials | 2 (40.00%) | 5.53% |
| Reviews | 0 (0.00%) | 6.00% |
| Case Studies | 0 (0.00%) | 4.05% |
| Observational | 0 (0.00%) | 0.25% |
| Other | 3 (60.00%) | 84.16% |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||