Page last updated: 2024-12-11
cgp 74588
Description
Research Excerpts
Clinical Trials
Roles
Classes
Pathways
Study Profile
Bioassays
Related Drugs
Related Conditions
Protein Interactions
Research Growth
Description
CGP 74588: a metabolite of STI-571; structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]
Cross-References
| ID Source | ID |
|---|---|
| PubMed CID | 9869737 |
| CHEMBL ID | 2386594 |
| CHEMBL ID | 3040018 |
| CHEBI ID | 169508 |
| SCHEMBL ID | 846536 |
| MeSH ID | M0437794 |
Synonyms (39)
| Synonym |
|---|
| 404844-02-6 |
| CHEBI:169508 |
| n-[4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl]-4-(piperazin-1-ylmethyl)benzamide |
| FT-0666167 |
| AKOS024573735 |
| bdbm50434582 |
| chembl2386594 , |
| norimatinib |
| n-desmethyl imatinib |
| n-[4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]phenyl]-4-(1-piperazinylmethyl)-benzamide |
| cgp-74588 |
| n-desmethyl gleevec |
| SCHEMBL846536 |
| sti-50900 |
| unii-6goh0n63qd |
| cgp 74588 |
| n-desmethylimatinib |
| sti-509-00 |
| benzamide, n-(4-methyl-3-((4-(3-pyridinyl)-2-pyrimidinyl)amino)phenyl)-4-(1-piperazinylmethyl)- |
| n desmethyl imatinib |
| 6goh0n63qd , |
| n-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenyl]-4-piperazin-1-ylmethyl-benzamide |
| n-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenyl]-4-(piperazin-1-ylmethyl)-benzamide |
| BQQYXPHRXIZMDM-UHFFFAOYSA-N |
| n-(4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)-4-(piperazin-1-ylmethyl)benzamide |
| AC-23925 |
| HY-G0017 |
| CHEMBL3040018 |
| imatinib metabolite n-desmethyl imatinib |
| DTXSID80193500 |
| n-(4-methyl-3-{[4-(pyridin-3-yl)pyrimidin-2-yl]amino}phenyl)-4-[(piperazin-1-yl)methyl]benzamide |
| AS-74968 |
| NCGC00485941-01 |
| cgp74588 |
| mfcd07369291 |
| n-(4-methyl-3-((4-(3-pyridinyl)-2-pyrimidinyl)amino)phenyl)-4-(1-piperazinylmethyl)benzamide |
| AMY38986 |
| Q27264884 |
| cgp-74588 (n-desmethyl imatinib) |
Research Excerpts
Toxicity
| Excerpt | Reference | Relevance |
|---|---|---|
| " iT with IM is a feasible and safe strategy for short-time 'bridging' management of patients with significant hematologic toxicity after standard daily dosing." | ( Intermittent dosage of imatinib mesylate in CML patients with a history of significant hematologic toxicity after standard dosing. Divoký, V; Egorin, MJ; Faber, E; Holzerová, M; Indrák, K; Jarosová, M; Maresová, I; Nausová, J; Rozmanová, S, 2006) | 0.33 |
| " We here describe the correlation of imatinib trough plasma concentrations (C(mins)) with clinical responses, event-free survival (EFS), and adverse events (AEs)." | ( Imatinib pharmacokinetics and its correlation with response and safety in chronic-phase chronic myeloid leukemia: a subanalysis of the IRIS study. Druker, BJ; Gathmann, I; Guilhot, F; Krahnke, T; Larson, RA; O'Brien, SG; Riviere, GJ; Wang, Y, 2008) | 0.35 |
Pharmacokinetics
| Excerpt | Reference | Relevance |
|---|---|---|
| "Despite the remarkable clinical response rates to imatinib in the treatment of bcr-abl leukemic patients, pharmacokinetic data on this relatively novel substance are needed to improve our understanding of the emergence of resistance, the interindividual variations of clinical response and the clinical and biologic relevance of its main metabolite N-desmethyl-imatinib." | ( Pharmacokinetics and cellular uptake of imatinib and its main metabolite CGP74588. Baskaynak, G; Bonin, Mv; Bornhäuser, M; Dörken, B; Ehninger, G; Jenke, A; Kreuzer, KA; le Coutre, P; Leopold, T; Ottmann, O; Pursche, S; Schleyer, E, 2004) | 0.32 |
| " Imatinib and CGP74588 (main metabolite of imatinib) concentrations were measured using LC/MS/MS method and pharmacokinetic parameters were estimated by a non-compartmental analysis." | ( Pharmacokinetic interaction between ketoconazole and imatinib mesylate (Glivec) in healthy subjects. Capdeville, R; Dutreix, C; Hayes, M; Mehring, G; Peng, B; Pokorny, R; Seiberling, M, 2004) | 0.32 |
| "The pharmacokinetic values for imatinib and CGP74588, respectively, were: maximum concentration (3,340 and 781 ng/ml), time to maximum concentration (2 h), half-life (18." | ( Pharmacokinetics of imatinib mesylate in end stage renal disease. A case study. Briasoulis, E; Karavasilis, V; Marselos, M; Pappas, P; Pavlidis, N, 2005) | 0.33 |
| " Population pharmacokinetic (PPK) studies evaluating the effect of population covariates on the pharmacokinetics of imatinib and its active metabolite have been developed in adults with chronic myeloid leukemia (CML) and gastrointestinal stromal tumor (GIST)." | ( Population pharmacokinetics of imatinib mesylate and its metabolite in children and young adults. Barrett, JS; Bernstein, M; Blaney, SM; Bond, M; Champagne, M; Fossler, MJ; Jayaraman, B; Menon-Andersen, D; Mondick, JT; Thompson, PA, 2009) | 0.35 |
| " Plasma imatinib and CGP74588 concentrations observed on day 1 and at steady-state were analyzed by a population pharmacokinetic method (NONMEM) to evaluate the effect of age, body weight, age, sex, albuminemia, plasma alpha1-acid glycoprotein (AGP), and eight polymorphisms corresponding to ABCB1, ABCG2, CYP3A4, CYP3A5, and AGP (pharmacogenetic data available for 46 of 67 patients)." | ( Population pharmacokinetics and pharmacogenetics of imatinib in children and adults. Azard, J; Barrois, M; Chatelut, E; Delbaldo, C; Geoerger, B; Kattygnarath, D; LeCesne, A; Petain, A; Séronie-Vivien, S; Vassal, G, 2008) | 0.35 |
| " When co-administered with voriconazole, pharmacokinetic parameters of imatinib were not significantly altered except for a 36." | ( Differential effects of ketoconazole, itraconazole and voriconazole on the pharmacokinetics of imatinib and its main metabolite GCP74588 in rat. Han, A; Hu, G; Kan, X; Lin, G; Qiu, X; Wang, C; Wang, Z; Xu, T, 2014) | 0.4 |
| " Future studies should focus on other pharmacokinetic processes so as to identify the major contributor to patient variability in imatinib plasma concentrations." | ( In Vivo Cytochrome P450 3A Isoenzyme Activity and Pharmacokinetics of Imatinib in Relation to Therapeutic Outcome in Patients With Chronic Myeloid Leukemia. Aagesen, J; Alsenhed, J; Aluthgedara, W; Bergquist, J; Gréen, H; Hägg, S; Johnsson, A; Lotfi, K; Olsson-Strömberg, U; Peterson, C; Richter, J; Sandstedt, A; Skoglund, K; Söderlund, S; Svedberg, A; Ubhayasekera, SJ; Vikingsson, S, 2016) | 0.43 |
Bioavailability
Dosage Studied
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]
Drug Classes (1)
| Class | Description |
|---|---|
| benzamides | |
| [compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res] | |
Pathways (1)
| Pathway | Proteins | Compounds |
|---|---|---|
| Imatinib Pathway, Pharmacokinetics/Pharmacodynamics | 12 | 2 |
Protein Targets (3)
Potency Measurements
| Protein | Taxonomy | Measurement | Average (µ) | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| PPM1D protein | Homo sapiens (human) | Potency | 41.5437 | 0.0052 | 9.4661 | 32.9993 | AID1347411 |
| Interferon beta | Homo sapiens (human) | Potency | 41.5437 | 0.0033 | 9.1582 | 39.8107 | AID1347411 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
Inhibition Measurements
| Protein | Taxonomy | Measurement | Average | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| Leucine-rich repeat serine/threonine-protein kinase 2 | Homo sapiens (human) | IC50 (µMol) | 3.9500 | 0.0004 | 0.3943 | 8.3000 | AID1233362; AID1233363 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
Biological Processes (122)
Molecular Functions (32)
Ceullar Components (43)
Bioassays (10)
| Assay ID | Title | Year | Journal | Article |
|---|---|---|---|---|
| AID1346987 | P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen | 2019 | Molecular pharmacology, 11, Volume: 96, Issue:5 | A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein. |
| AID1346986 | P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen | 2019 | Molecular pharmacology, 11, Volume: 96, Issue:5 | A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein. |
| AID1296008 | Cytotoxic Profiling of Annotated Libraries Using Quantitative High-Throughput Screening | 2020 | SLAS discovery : advancing life sciences R & D, 01, Volume: 25, Issue:1 | Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening. |
| AID1347160 | Primary screen NINDS Rhodamine qHTS for Zika virus inhibitors | 2020 | Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49 | Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors. |
| AID1347159 | Primary screen GU Rhodamine qHTS for Zika virus inhibitors: Unlinked NS2B-NS3 protease assay | 2020 | Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49 | Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors. |
| AID1233362 | Inhibition of wild type LRRK2 (unknown origin) assessed as inhibition of LRRKtide phosphorylation after 120 mins by radiometric assay in presence of [gamma-33P]-ATP | 2015 | Bioorganic & medicinal chemistry letters, Jul-01, Volume: 25, Issue:13 | Discovery of LRRK2 inhibitors using sequential in silico joint pharmacophore space (JPS) and ensemble docking. |
| AID1233363 | Inhibition of LRRK2 G2019S mutant (unknown origin) | 2015 | Bioorganic & medicinal chemistry letters, Jul-01, Volume: 25, Issue:13 | Discovery of LRRK2 inhibitors using sequential in silico joint pharmacophore space (JPS) and ensemble docking. |
| AID1233367 | Competitive inhibition of wild type LRRK2 (unknown origin) using LRRKtide as substrate after 150 mins in presence of [gamma-33P]-ATP | 2015 | Bioorganic & medicinal chemistry letters, Jul-01, Volume: 25, Issue:13 | Discovery of LRRK2 inhibitors using sequential in silico joint pharmacophore space (JPS) and ensemble docking. |
| AID1233365 | Selectivity ratio of IC50 for wild type LRRK2 (unknown origin) to IC50 for LRRK2 G2019S mutant (unknown origin) | 2015 | Bioorganic & medicinal chemistry letters, Jul-01, Volume: 25, Issue:13 | Discovery of LRRK2 inhibitors using sequential in silico joint pharmacophore space (JPS) and ensemble docking. |
| AID1347411 | qHTS to identify inhibitors of the type 1 interferon - major histocompatibility complex class I in skeletal muscle: primary screen against the NCATS Mechanism Interrogation Plate v5.0 (MIPE) Libary | 2020 | ACS chemical biology, 07-17, Volume: 15, Issue:7 | High-Throughput Screening to Identify Inhibitors of the Type I Interferon-Major Histocompatibility Complex Class I Pathway in Skeletal Muscle. |
| [information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||||
Research
Studies (39)
| Timeframe | Studies, This Drug (%) | All Drugs % |
|---|---|---|
| pre-1990 | 0 (0.00) | 18.7374 |
| 1990's | 0 (0.00) | 18.2507 |
| 2000's | 20 (51.28) | 29.6817 |
| 2010's | 16 (41.03) | 24.3611 |
| 2020's | 3 (7.69) | 2.80 |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||
Study Types
| Publication Type | This drug (%) | All Drugs (%) |
|---|---|---|
| Trials | 9 (22.50%) | 5.53% |
| Reviews | 2 (5.00%) | 6.00% |
| Case Studies | 6 (15.00%) | 4.05% |
| Observational | 0 (0.00%) | 0.25% |
| Other | 23 (57.50%) | 84.16% |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||