Page last updated: 2024-11-13
frax597
Description
Research Excerpts
Clinical Trials
Roles
Classes
Pathways
Study Profile
Bioassays
Related Drugs
Related Conditions
Protein Interactions
Research Growth
Market Indicators
Description
FRAX597: structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]
Cross-References
| ID Source | ID |
|---|---|
| PubMed CID | 70934541 |
| CHEMBL ID | 3609327 |
| SCHEMBL ID | 13554062 |
| MeSH ID | M0589352 |
Synonyms (31)
| Synonym |
|---|
| S7271 , |
| frax597 |
| CS-1977 |
| HY-15542A |
| SCHEMBL13554062 |
| 1286739-19-2 |
| AC-29026 |
| CHEMBL3609327 , |
| AKOS025404924 |
| gtpl8939 |
| 6-[2-chloro-4-(1,3-thiazol-5-yl)phenyl]-8-ethyl-2-[4-(4-methylpiperazin-1-yl)anilino]pyrido[2,3-d]pyrimidin-7-one |
| frax 597 |
| 6-[2-chloro-4-(5-thiazolyl)phenyl]-8-ethyl-2-[[4-(4-methyl-1-piperazinyl)phenyl]amino]pyrido[2,3-d]pyrimidin-7-(8h)-one |
| pyrido[2,3-d]pyrimidin-7(8h)-one, 6-[2-chloro-4-(5-thiazolyl)phenyl]-8-ethyl-2-[[4-(4-methyl-1-piperazinyl)phenyl]amino]- |
| AS-75080 |
| bdbm50112347 |
| NCGC00389582-02 |
| mfcd25976723 |
| 6-(2-chloro-4-(thiazol-5-yl)phenyl)-8-ethyl-2-((4-(4-methylpiperazin-1-yl)phenyl)amino)pyrido[2,3-d]pyrimidin-7(8h)-one |
| EX-A2219 |
| Q27077742 |
| BCP12649 |
| SB19060 |
| 6-[2-chloro-4-(1,3-thiazol-5-yl)phenyl]-8-ethyl-2-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-7h,8h-pyrido[2,3-d]pyrimidin-7-one |
| HMS3673K09 |
| CCG-270039 |
| C72167 |
| frax-597 |
| NCGC00389582-01 |
| A888991 |
| 6-(2-chloro-4-thiazol-5-yl-phenyl)-8-ethyl-2-[4-(4-methylpiperazin-1-yl)anilino]pyrido[2,3-d]pyrimidin-7-one |
Research Excerpts
Compound-Compound Interactions
FRAX597 inhibited pancreatic cancer proliferation in vitro and inhibited tumour growth in vivo. When combined with gemcitabine, FRAx597 synergistically inhibited Pancreatic cancer.
| Excerpt | Reference | Relevance |
|---|---|---|
| " The effect of inhibition of PAK1 by either shRNA knock-down (KD), or by a selective inhibitor, FRAX597, alone or in combination with gemcitabine, on cell proliferation and migration/invasion was measured by thymidine uptake and Boyden chamber assays, respectively." | ( FRAX597, a PAK1 inhibitor, synergistically reduces pancreatic cancer growth when combined with gemcitabine. Baldwin, GS; He, H; Lowy, AM; Nikfarjam, M; Patel, O; Yeo, D, 2016) | 2.1 |
| " When combined with gemcitabine, FRAX597 synergistically inhibited pancreatic cancer proliferation in vitro and inhibited tumour growth in vivo." | ( FRAX597, a PAK1 inhibitor, synergistically reduces pancreatic cancer growth when combined with gemcitabine. Baldwin, GS; He, H; Lowy, AM; Nikfarjam, M; Patel, O; Yeo, D, 2016) | 2.16 |
Bioavailability
| Excerpt | Reference | Relevance |
|---|---|---|
| "The ATP-binding cassette transporter P-glycoprotein (P-gp) is known to limit both brain penetration and oral bioavailability of many chemotherapy drugs." | ( A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein. Ambudkar, SV; Brimacombe, KR; Chen, L; Gottesman, MM; Guha, R; Hall, MD; Klumpp-Thomas, C; Lee, OW; Lee, TD; Lusvarghi, S; Robey, RW; Shen, M; Tebase, BG, 2019) | 0.51 |
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]
Protein Targets (11)
Potency Measurements
| Protein | Taxonomy | Measurement | Average (µ) | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| PPM1D protein | Homo sapiens (human) | Potency | 7.3876 | 0.0052 | 9.4661 | 32.9993 | AID1347411 |
| cytochrome P450 family 3 subfamily A polypeptide 4 | Homo sapiens (human) | Potency | 2.3919 | 0.0123 | 7.9835 | 43.2770 | AID1645841 |
| G | Vesicular stomatitis virus | Potency | 6.0081 | 0.0123 | 8.9648 | 39.8107 | AID1645842 |
| Interferon beta | Homo sapiens (human) | Potency | 7.0427 | 0.0033 | 9.1582 | 39.8107 | AID1347411; AID1645842 |
| HLA class I histocompatibility antigen, B alpha chain | Homo sapiens (human) | Potency | 6.0081 | 0.0123 | 8.9648 | 39.8107 | AID1645842 |
| Inositol hexakisphosphate kinase 1 | Homo sapiens (human) | Potency | 6.0081 | 0.0123 | 8.9648 | 39.8107 | AID1645842 |
| cytochrome P450 2C9, partial | Homo sapiens (human) | Potency | 6.0081 | 0.0123 | 8.9648 | 39.8107 | AID1645842 |
| [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) |
|---|---|---|---|---|---|---|---|
| Serine/threonine-protein kinase PAK 3 | Homo sapiens (human) | IC50 (µMol) | 1.6804 | 0.0002 | 0.0263 | 0.0990 | AID1242473; AID1737261; AID1802401 |
| Serine/threonine-protein kinase PAK 4 | Homo sapiens (human) | IC50 (µMol) | 4.0080 | 0.0010 | 0.5686 | 6.9000 | AID1242474; AID1802401 |
| Serine/threonine-protein kinase PAK 1 | Homo sapiens (human) | IC50 (µMol) | 1.0185 | 0.0002 | 0.3001 | 2.5000 | AID1242471; AID1326054; AID1326055; AID1424468; AID1721848; AID1737259; AID1802401 |
| Serine/threonine-protein kinase PAK 2 | Homo sapiens (human) | IC50 (µMol) | 1.6786 | 0.0010 | 0.0281 | 0.1900 | AID1242472; AID1737260; AID1802401 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
Biological Processes (105)
Molecular Functions (32)
Ceullar Components (41)
Bioassays (36)
| Assay ID | Title | Year | Journal | Article |
|---|---|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| AID1737268 | Inhibition of PAK1 in human MDA-MB-231 cells assessed as reduction in MAPK-ERK signaling measured after 24 hrs by Western blot analysis | 2020 | European journal of medicinal chemistry, May-15, Volume: 194 | Design, synthesis and biological evaluation of 1H-pyrazolo [3,4-d]pyrimidine derivatives as PAK1 inhibitors that trigger apoptosis, ER stress and anti-migration effect in MDA-MB-231 cells. |
| AID1242474 | Inhibition of recombinant human PAK4 by Z'-LYTE assay | 2015 | ACS medicinal chemistry letters, Jul-09, Volume: 6, Issue:7 | Optimization of a Dibenzodiazepine Hit to a Potent and Selective Allosteric PAK1 Inhibitor. |
| AID1721849 | Antiproliferative activity against human MDA-MB-231 cells assessed as cell growth inhibition | 2020 | Bioorganic & medicinal chemistry letters, 09-01, Volume: 30, Issue:17 | Design, synthesis and biological evaluation of 2-indolinone derivatives as PAK1 inhibitors in MDA-MB-231 cells. |
| AID1326058 | Selectivity ratio of IC50 for FGFR1 (unknown origin) to IC50 for PAK1 (unknown origin) | 2016 | ACS medicinal chemistry letters, Dec-08, Volume: 7, Issue:12 | Optimization of Highly Kinase Selective Bis-anilino Pyrimidine PAK1 Inhibitors. |
| AID1737266 | Inhibition of PAK1 phosphorylation at Ser199 residues in human MDA-MB-231 cells at 2.5 to 10 uM measured after 24 hrs by Western blot analysis | 2020 | European journal of medicinal chemistry, May-15, Volume: 194 | Design, synthesis and biological evaluation of 1H-pyrazolo [3,4-d]pyrimidine derivatives as PAK1 inhibitors that trigger apoptosis, ER stress and anti-migration effect in MDA-MB-231 cells. |
| AID1737274 | Inhibition of PAK1 in human MDA-MB-231 cells assessed as reduction in c-Raf phosphorylation at Ser259 residues at 2.5 to 10 uM measured after 24 hrs by Western blot analysis | 2020 | European journal of medicinal chemistry, May-15, Volume: 194 | Design, synthesis and biological evaluation of 1H-pyrazolo [3,4-d]pyrimidine derivatives as PAK1 inhibitors that trigger apoptosis, ER stress and anti-migration effect in MDA-MB-231 cells. |
| AID1326062 | Distribution coefficient, logD of the compound | 2016 | ACS medicinal chemistry letters, Dec-08, Volume: 7, Issue:12 | Optimization of Highly Kinase Selective Bis-anilino Pyrimidine PAK1 Inhibitors. |
| AID1721848 | Inhibition of PAK1 (unknown origin) | 2020 | Bioorganic & medicinal chemistry letters, 09-01, Volume: 30, Issue:17 | Design, synthesis and biological evaluation of 2-indolinone derivatives as PAK1 inhibitors in MDA-MB-231 cells. |
| AID1737273 | Inhibition of PAK1 in human MDA-MB-231 cells assessed as reduction in ERK expression at 2.5 to 10 uM measured after 24 hrs by Western blot analysis | 2020 | European journal of medicinal chemistry, May-15, Volume: 194 | Design, synthesis and biological evaluation of 1H-pyrazolo [3,4-d]pyrimidine derivatives as PAK1 inhibitors that trigger apoptosis, ER stress and anti-migration effect in MDA-MB-231 cells. |
| AID1326059 | Selectivity ratio of IC50 for KDR (unknown origin) to IC50 for PAK1 (unknown origin) | 2016 | ACS medicinal chemistry letters, Dec-08, Volume: 7, Issue:12 | Optimization of Highly Kinase Selective Bis-anilino Pyrimidine PAK1 Inhibitors. |
| AID1737259 | Inhibition of PAK1 (unknown origin) using lipid substrate measured after 40 mins by ADP-glo kinase assay | 2020 | European journal of medicinal chemistry, May-15, Volume: 194 | Design, synthesis and biological evaluation of 1H-pyrazolo [3,4-d]pyrimidine derivatives as PAK1 inhibitors that trigger apoptosis, ER stress and anti-migration effect in MDA-MB-231 cells. |
| AID1424468 | Inhibition of GST-tagged recombinant human PAK1 by Z'-LYTE functional biochemical assay | 2017 | European journal of medicinal chemistry, Dec-15, Volume: 142 | From bench (laboratory) to bed (hospital/home): How to explore effective natural and synthetic PAK1-blockers/longevity-promoters for cancer therapy. |
| AID1242471 | Inhibition of recombinant human PAK1 by Z'-LYTE assay | 2015 | ACS medicinal chemistry letters, Jul-09, Volume: 6, Issue:7 | Optimization of a Dibenzodiazepine Hit to a Potent and Selective Allosteric PAK1 Inhibitor. |
| AID1737275 | Inhibition of PAK1 in human MDA-MB-231 cells assessed as reduction in MEK1/2 phosphorylation at ser217/221 residues at 2.5 to 10 uM measured after 24 hrs by Western blot analysis | 2020 | European journal of medicinal chemistry, May-15, Volume: 194 | Design, synthesis and biological evaluation of 1H-pyrazolo [3,4-d]pyrimidine derivatives as PAK1 inhibitors that trigger apoptosis, ER stress and anti-migration effect in MDA-MB-231 cells. |
| AID1737263 | Down regulation of PAK1 expression in human MDA-MB-231 cells at 5 uM measured after 24 hrs by immunofluorescence analysis | 2020 | European journal of medicinal chemistry, May-15, Volume: 194 | Design, synthesis and biological evaluation of 1H-pyrazolo [3,4-d]pyrimidine derivatives as PAK1 inhibitors that trigger apoptosis, ER stress and anti-migration effect in MDA-MB-231 cells. |
| AID1242473 | Inhibition of recombinant human PAK3 by Z'-LYTE assay | 2015 | ACS medicinal chemistry letters, Jul-09, Volume: 6, Issue:7 | Optimization of a Dibenzodiazepine Hit to a Potent and Selective Allosteric PAK1 Inhibitor. |
| AID1737276 | Inhibition of PAK1 in human MDA-MB-231 cells assessed as reduction in ERK1/2 phosphorylation at Thr202/Tyr204 residues at 2.5 to 10 uM measured after 24 hrs by Western blot analysis | 2020 | European journal of medicinal chemistry, May-15, Volume: 194 | Design, synthesis and biological evaluation of 1H-pyrazolo [3,4-d]pyrimidine derivatives as PAK1 inhibitors that trigger apoptosis, ER stress and anti-migration effect in MDA-MB-231 cells. |
| AID1737261 | Inhibition of PAK3 (unknown origin) using lipid substrate measured after 40 mins by ADP-glo kinase assay | 2020 | European journal of medicinal chemistry, May-15, Volume: 194 | Design, synthesis and biological evaluation of 1H-pyrazolo [3,4-d]pyrimidine derivatives as PAK1 inhibitors that trigger apoptosis, ER stress and anti-migration effect in MDA-MB-231 cells. |
| AID1326055 | Inhibition of PAK1 phosphorylation in human MCF10A cells | 2016 | ACS medicinal chemistry letters, Dec-08, Volume: 7, Issue:12 | Optimization of Highly Kinase Selective Bis-anilino Pyrimidine PAK1 Inhibitors. |
| AID1737260 | Inhibition of PAK2 (unknown origin) using lipid substrate measured after 40 mins by ADP-glo kinase assay | 2020 | European journal of medicinal chemistry, May-15, Volume: 194 | Design, synthesis and biological evaluation of 1H-pyrazolo [3,4-d]pyrimidine derivatives as PAK1 inhibitors that trigger apoptosis, ER stress and anti-migration effect in MDA-MB-231 cells. |
| AID1326054 | Inhibition of PAK1 (unknown origin) by ATP-kinaseGlo assay | 2016 | ACS medicinal chemistry letters, Dec-08, Volume: 7, Issue:12 | Optimization of Highly Kinase Selective Bis-anilino Pyrimidine PAK1 Inhibitors. |
| AID1737267 | Inhibition of PAK1 phosphorylation at Thr212 residues in human MDA-MB-231 cells at 2.5 to 10 uM measured after 24 hrs by Western blot analysis | 2020 | European journal of medicinal chemistry, May-15, Volume: 194 | Design, synthesis and biological evaluation of 1H-pyrazolo [3,4-d]pyrimidine derivatives as PAK1 inhibitors that trigger apoptosis, ER stress and anti-migration effect in MDA-MB-231 cells. |
| AID1326060 | Selectivity ratio of IC50 for PAK4 (unknown origin) to IC50 for PAK1 (unknown origin) | 2016 | ACS medicinal chemistry letters, Dec-08, Volume: 7, Issue:12 | Optimization of Highly Kinase Selective Bis-anilino Pyrimidine PAK1 Inhibitors. |
| AID1326061 | Selectivity ratio of IC50 for SRC (unknown origin) to IC50 for PAK1 (unknown origin) | 2016 | ACS medicinal chemistry letters, Dec-08, Volume: 7, Issue:12 | Optimization of Highly Kinase Selective Bis-anilino Pyrimidine PAK1 Inhibitors. |
| AID1242472 | Inhibition of recombinant human PAK2 by Z'-LYTE assay | 2015 | ACS medicinal chemistry letters, Jul-09, Volume: 6, Issue:7 | Optimization of a Dibenzodiazepine Hit to a Potent and Selective Allosteric PAK1 Inhibitor. |
| AID1802401 | Z'-LYTEBiochemical Assay from Article 10.1074/jbc.M113.510933: \\FRAX597, a small molecule inhibitor of the p21-activated kinases, inhibits tumorigenesis of neurofibromatosis type 2 (NF2)-associated Schwannomas.\\ | 2013 | The Journal of biological chemistry, Oct-04, Volume: 288, Issue:40 | FRAX597, a small molecule inhibitor of the p21-activated kinases, inhibits tumorigenesis of neurofibromatosis type 2 (NF2)-associated Schwannomas. |
| AID1345771 | Human p21 (RAC1) activated kinase 2 (PAKA subfamily) | 2013 | The Journal of biological chemistry, Oct-04, Volume: 288, Issue:40 | FRAX597, a small molecule inhibitor of the p21-activated kinases, inhibits tumorigenesis of neurofibromatosis type 2 (NF2)-associated Schwannomas. |
| AID1345767 | Human p21 (RAC1) activated kinase 3 (PAKA subfamily) | 2013 | The Journal of biological chemistry, Oct-04, Volume: 288, Issue:40 | FRAX597, a small molecule inhibitor of the p21-activated kinases, inhibits tumorigenesis of neurofibromatosis type 2 (NF2)-associated Schwannomas. |
| AID1345729 | Human p21 (RAC1) activated kinase 4 (PAKB subfamily) | 2013 | The Journal of biological chemistry, Oct-04, Volume: 288, Issue:40 | FRAX597, a small molecule inhibitor of the p21-activated kinases, inhibits tumorigenesis of neurofibromatosis type 2 (NF2)-associated Schwannomas. |
| AID1345761 | Human p21 (RAC1) activated kinase 1 (PAKA subfamily) | 2013 | The Journal of biological chemistry, Oct-04, Volume: 288, Issue:40 | FRAX597, a small molecule inhibitor of the p21-activated kinases, inhibits tumorigenesis of neurofibromatosis type 2 (NF2)-associated Schwannomas. |
| [information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||||
Research
Studies (16)
| Timeframe | Studies, This Drug (%) | All Drugs % |
|---|---|---|
| pre-1990 | 0 (0.00) | 18.7374 |
| 1990's | 0 (0.00) | 18.2507 |
| 2000's | 0 (0.00) | 29.6817 |
| 2010's | 11 (68.75) | 24.3611 |
| 2020's | 5 (31.25) | 2.80 |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||
Market Indicators
Research Demand Index: 22.26
According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be moderate demand-to-supply ratio for research on this compound.
| This Compound (22.26) All Compounds (24.57) |
Study Types
| Publication Type | This drug (%) | All Drugs (%) |
|---|---|---|
| Trials | 0 (0.00%) | 5.53% |
| Reviews | 1 (6.25%) | 6.00% |
| Case Studies | 0 (0.00%) | 4.05% |
| Observational | 0 (0.00%) | 0.25% |
| Other | 15 (93.75%) | 84.16% |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||