PF-543: Sphingosine Kinase 1 Selective Inhibitor; structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]
| ID Source | ID |
|---|---|
| PubMed CID | 66577038 |
| CHEMBL ID | 3134157 |
| CHEBI ID | 131144 |
| SCHEMBL ID | 17786131 |
| MeSH ID | M0575093 |
| Synonym |
|---|
| HY-15425 |
| pf-543 |
| CHEBI:131144 |
| CS-0869 |
| CHEMBL3134157 , |
| [(2r)-1-[(4-{3-[(benzenesulfonyl)methyl]-5-methylphenoxymethyl}phenyl)methyl]pyrrolidin-2-yl]methanol |
| sphingosine kinase 1 inhibitor ii |
| compound 22a [pmid: 22397330] |
| BRD-K79877282-001-01-9 |
| pf 543 |
| gtpl6623 |
| {(2r)-1-[4-({3-methyl-5-[(phenylsulfonyl)methyl]phenoxy}methyl)benzyl]pyrrolidin-2-yl}methanol |
| 1415562-82-1 |
| pf543 |
| SCHEMBL17786131 |
| bdbm50041978 |
| DTXSID90735359 |
| [(2r)-1-{[4-({3-[(benzenesulfonyl)methyl]-5-methylphenoxy}methyl)phenyl]methyl}pyrrolidin-2-yl]methanol |
| AKOS030526503 |
| 2-pyrrolidinemethanol, 1-[[4-[[3-methyl-5-[(phenylsulfonyl)methyl]phenoxy]methyl]phenyl]methyl]-, (2r)- |
| (r)-(1-(4-((3-methyl-5-((phenylsulfonyl)methyl)phenoxy)methyl)benzyl)pyrrolidin-2-yl)methanol |
| NCGC00346972-04 |
| SW218168-2 |
| (2r)-1-[[4-[[3-methyl-5-[(phenylsulfonyl)methyl]phenoxy]methyl]phenyl]methyl]-2-pyrrolidinemethanol |
| BCP07072 |
| EX-A7103 |
| S7177 |
| Q27088335 |
| CCG-269412 |
| [(2r)-1-[[4-[[3-(benzenesulfonylmethyl)-5-methylphenoxy]methyl]phenyl]methyl]pyrrolidin-2-yl]methanol |
| AS-77597 |
| 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 |
| Class | Description |
|---|---|
| sulfonamide | An amide of a sulfonic acid RS(=O)2NR'2. |
| [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] | |
| Protein | Taxonomy | Measurement | Average | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| Tyrosine-protein kinase ABL1 | Homo sapiens (human) | IC50 (µMol) | 10.0000 | 0.0001 | 0.7128 | 10.0000 | AID1908703 |
| Epidermal growth factor receptor | Homo sapiens (human) | IC50 (µMol) | 10.0000 | 0.0000 | 0.5369 | 10.0000 | AID1908699 |
| Receptor tyrosine-protein kinase erbB-2 | Homo sapiens (human) | IC50 (µMol) | 10.0000 | 0.0001 | 0.5453 | 10.0000 | AID1908700 |
| Insulin receptor | Homo sapiens (human) | IC50 (µMol) | 10.0000 | 0.0017 | 0.8479 | 10.0000 | AID1908708 |
| Macrophage colony-stimulating factor 1 receptor | Homo sapiens (human) | IC50 (µMol) | 10.0000 | 0.0006 | 0.5676 | 5.5450 | AID1908714 |
| Proto-oncogene tyrosine-protein kinase receptor Ret | Homo sapiens (human) | IC50 (µMol) | 10.0000 | 0.0001 | 0.3484 | 3.5970 | AID1908697 |
| Insulin-like growth factor 1 receptor | Homo sapiens (human) | IC50 (µMol) | 10.0000 | 0.0003 | 0.4308 | 8.0000 | AID1908707 |
| Platelet-derived growth factor receptor beta | Homo sapiens (human) | IC50 (µMol) | 10.0000 | 0.0006 | 0.8007 | 8.5000 | AID1908696 |
| Fibroblast growth factor receptor 1 | Homo sapiens (human) | IC50 (µMol) | 10.0000 | 0.0002 | 0.9420 | 10.0000 | AID1908709 |
| Proto-oncogene tyrosine-protein kinase Src | Homo sapiens (human) | IC50 (µMol) | 10.0000 | 0.0002 | 0.5335 | 10.0000 | AID1908702 |
| Platelet-derived growth factor receptor alpha | Homo sapiens (human) | IC50 (µMol) | 10.0000 | 0.0001 | 0.4912 | 10.0000 | AID1908695 |
| Vascular endothelial growth factor receptor 1 | Homo sapiens (human) | IC50 (µMol) | 10.0000 | 0.0001 | 0.2914 | 7.0000 | AID1908692 |
| Fibroblast growth factor receptor 2 | Homo sapiens (human) | IC50 (µMol) | 10.0000 | 0.0004 | 0.3276 | 8.6200 | AID1908710 |
| Fibroblast growth factor receptor 4 | Homo sapiens (human) | IC50 (µMol) | 10.0000 | 0.0008 | 0.6217 | 8.6200 | AID1908712 |
| Fibroblast growth factor receptor 3 | Homo sapiens (human) | IC50 (µMol) | 10.0000 | 0.0004 | 0.2863 | 8.6200 | AID1908711 |
| Ephrin type-A receptor 2 | Homo sapiens (human) | IC50 (µMol) | 10.0000 | 0.0008 | 0.0436 | 0.2626 | AID1908704 |
| Ephrin type-B receptor 2 | Homo sapiens (human) | IC50 (µMol) | 10.0000 | 0.0025 | 1.5875 | 8.5000 | AID1908705 |
| Vascular endothelial growth factor receptor 3 | Homo sapiens (human) | IC50 (µMol) | 10.0000 | 0.0001 | 0.2264 | 4.9000 | AID1908694 |
| Vascular endothelial growth factor receptor 2 | Homo sapiens (human) | IC50 (µMol) | 10.0000 | 0.0000 | 0.4830 | 8.8000 | AID1908693 |
| Receptor-type tyrosine-protein kinase FLT3 | Homo sapiens (human) | IC50 (µMol) | 10.0000 | 0.0001 | 0.3275 | 9.5480 | AID1908698 |
| Tyrosine-protein kinase BTK | Homo sapiens (human) | IC50 (µMol) | 10.0000 | 0.0001 | 0.2557 | 7.6000 | AID1908713 |
| Activated CDC42 kinase 1 | Homo sapiens (human) | IC50 (µMol) | 10.0000 | 0.0027 | 0.3447 | 3.1000 | AID1908706 |
| Receptor tyrosine-protein kinase erbB-4 | Homo sapiens (human) | IC50 (µMol) | 10.0000 | 0.0001 | 0.1736 | 2.5900 | AID1908701 |
| Sphingosine kinase 1 | Mus musculus (house mouse) | Ki | 0.0036 | 0.0036 | 0.0036 | 0.0036 | AID1304649 |
| Sphingosine kinase 2 | Homo sapiens (human) | IC50 (µMol) | 6.6395 | 0.3560 | 3.5352 | 10.0000 | AID1277462; AID1277483; AID1442126; AID1478825; AID1593534; AID1718951; AID1908689; AID1908779 |
| Sphingosine kinase 2 | Homo sapiens (human) | Ki | 0.0036 | 0.0036 | 8.8052 | 10.0000 | AID1593544 |
| Sphingosine kinase 1 | Homo sapiens (human) | IC50 (µMol) | 0.0422 | 0.0008 | 1.3039 | 7.1000 | AID1077891; AID1277480; AID1277481; AID1277482; AID1442124; AID1442125; AID1442127; AID1442134; AID1478824; AID1593533; AID1718950; AID1908691; AID1908777 |
| Sphingosine kinase 1 | Homo sapiens (human) | Ki | 0.0037 | 0.0036 | 3.0956 | 10.0000 | AID1176725; AID1199975; AID1277461; AID1482728; AID1501055; AID1694026; AID1705514; AID1730252 |
| [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) |
|---|---|---|---|---|---|---|---|
| Sphingosine kinase 1 | Homo sapiens (human) | Kd | 0.0050 | 0.0050 | 0.0050 | 0.0050 | AID1405277 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
| Assay ID | Title | Year | Journal | Article |
|---|---|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| AID1593534 | Inhibition of recombinant human full-length N-terminal His-tagged SK2 expressed in baculovirus infected Sf9 insect cells using Sph as substrate measured after 30 mins in presence of [gamma32P]ATP by Cerenkov counting analysis | 2019 | Journal of medicinal chemistry, 04-11, Volume: 62, Issue:7 | Topographical Mapping of Isoform-Selectivity Determinants for J-Channel-Binding Inhibitors of Sphingosine Kinases 1 and 2. |
| AID1908735 | Induction of apoptosis in human HT-29 cells assessed as increase in caspase 3 cleavage at 10 uM measured after 48 hrs by western blot analysis | |||
| AID1593544 | Inhibition of SK2 (unknown origin) | 2019 | Journal of medicinal chemistry, 04-11, Volume: 62, Issue:7 | Topographical Mapping of Isoform-Selectivity Determinants for J-Channel-Binding Inhibitors of Sphingosine Kinases 1 and 2. |
| AID1593533 | Inhibition of GFP-tagged SK1 (unknown origin) expressed in HEK293 cells using Sph as substrate measured after 30 mins in presence of [gamma32P]ATP by Cerenkov counting analysis | 2019 | Journal of medicinal chemistry, 04-11, Volume: 62, Issue:7 | Topographical Mapping of Isoform-Selectivity Determinants for J-Channel-Binding Inhibitors of Sphingosine Kinases 1 and 2. |
| AID1908775 | Induction of apoptosis in human MDA-MB-231 cells assessed as necrotic cells at 10 uM incubated for 48 hrs by Annexin V-FITC/PI staining based flow cytometry (Rvb = 1.42 %) | |||
| AID1908779 | Inhibition of SPHK2 (unknown origin) | |||
| AID1908762 | Antitumor activity against human HT-29 cells xenografted in BALB/c mouse assessed as tumor growth inhibition at 50 mg/kg/day, ip for 3 weeks and measured every 3 days by caliper method | |||
| AID1908708 | Inhibition of Insulin receptor (unknown origin) | |||
| AID1176725 | Inhibition of His6 tagged human SphK1 expressed in Sf21 cells using FITC-sphingosine as substrate preincubated for 90 mins prior substrate addition by Caliper assay | 2014 | ACS medicinal chemistry letters, Dec-11, Volume: 5, Issue:12 | Crystal Structure of Sphingosine Kinase 1 with PF-543. |
| AID1908697 | Inhibition of RET (unknown origin) | |||
| AID1442124 | Inhibition of human C-terminal His6-tagged SPHK1 expressed in fall armyworm sf9 cells assessed as reduction in S1P formation using sphingosine as substrate after 1 hr by FITC-based caliper assay | 2017 | Journal of medicinal chemistry, 03-23, Volume: 60, Issue:6 | Discovery of a Potent and Selective Sphingosine Kinase 1 Inhibitor through the Molecular Combination of Chemotype-Distinct Screening Hits. |
| AID1908699 | Inhibition of EGFR (unknown origin) | |||
| AID1277466 | Induction of SK1 degradation in HEK293 cells at 10 uM after 16 hrs by western blotting analysis in presence of proteasome inhibitor MG132 | 2016 | Journal of medicinal chemistry, Feb-11, Volume: 59, Issue:3 | From Sphingosine Kinase to Dihydroceramide Desaturase: A Structure-Activity Relationship (SAR) Study of the Enzyme Inhibitory and Anticancer Activity of 4-((4-(4-Chlorophenyl)thiazol-2-yl)amino)phenol (SKI-II). |
| AID1908713 | Inhibition of BTK (unknown origin) | |||
| AID1908743 | Antimigratory activity against human MDA-MB-231 cells assessed as inhibition of cell migration in human MDA-MB-231 cells at 40 uM incubated for 15 hrs by wound healing assay | |||
| AID1908706 | Inhibition of ACK1 (unknown origin) | |||
| AID1908703 | Inhibition of ABL (unknown origin) | |||
| AID1908770 | Antimetastatic activity against human MDA-MB-231 cells xenografted in BALB/c mouse assessed as decrease in plasma S1P levels at 100 mg/kg, ip for 28 days | |||
| AID1908693 | Inhibition of VEGFR2 (unknown origin) | |||
| AID1908727 | Induction of cell cycle arrest at G0/G1 phase in human HT-29 cells assessed as reduction in CDK6 expression at 10 to 30 uM incubated for 24 hrs by Western blot analysis | |||
| AID1442127 | Inhibition of SPHK1 in human MDA1483 cells using C17-sphingosine as substrate assessed as reduction in C17-S1P formation preincubated for 30 mins with substrate measured after 15 mins by LC-MS analysis | 2017 | Journal of medicinal chemistry, 03-23, Volume: 60, Issue:6 | Discovery of a Potent and Selective Sphingosine Kinase 1 Inhibitor through the Molecular Combination of Chemotype-Distinct Screening Hits. |
| AID1730252 | Competitive-inhibition of recombinant human C-terminal His6-tagged Sphk1 expressed in baculovirus infected Sf21 insect cells using varying levels of sphingosine as substrate measured after 30 mins by LC-MS analysis | 2021 | European journal of medicinal chemistry, Feb-15, Volume: 212 | Probing the substitution pattern of indole-based scaffold reveals potent and selective sphingosine kinase 2 inhibitors. |
| AID1908744 | Tmax in mouse at 20 mg/kg, po | |||
| AID1908704 | Inhibition of EPHA2 (unknown origin) | |||
| AID1593535 | Inhibition of recombinant human full-length N-terminal His-tagged SK2 expressed in baculovirus infected Sf9 insect cells at 5 uM using Sph as substrate measured after 30 mins in presence of [gamma32P]ATP by Cerenkov counting analysis relative to control | 2019 | Journal of medicinal chemistry, 04-11, Volume: 62, Issue:7 | Topographical Mapping of Isoform-Selectivity Determinants for J-Channel-Binding Inhibitors of Sphingosine Kinases 1 and 2. |
| AID1908698 | Inhibition of FLT3 (unknown origin) | |||
| AID1908718 | Antiproliferative activity against human MDA-MB-231 cells for 72 hrs by SRB assay | |||
| AID1442125 | Inhibition of human C-terminal His6-tagged SPHK1 expressed in fall armyworm sf9 cells assessed as reduction in ADP formation using sphingosine as substrate preincubated for 15 mins followed by substrate addition after 1 hr by transcreener-based fluorescen | 2017 | Journal of medicinal chemistry, 03-23, Volume: 60, Issue:6 | Discovery of a Potent and Selective Sphingosine Kinase 1 Inhibitor through the Molecular Combination of Chemotype-Distinct Screening Hits. |
| AID1277464 | Inhibition of recombinant human SK2 assessed as production of [32P] S1P using sphingosine as substrate at 10 uM by TLC method in presence of 100 uM [gamma32P]-ATP relative to control | 2016 | Journal of medicinal chemistry, Feb-11, Volume: 59, Issue:3 | From Sphingosine Kinase to Dihydroceramide Desaturase: A Structure-Activity Relationship (SAR) Study of the Enzyme Inhibitory and Anticancer Activity of 4-((4-(4-Chlorophenyl)thiazol-2-yl)amino)phenol (SKI-II). |
| AID1908758 | Clearance in mouse at 2 mg/kg, iv | |||
| AID1277463 | Inhibition of recombinant His-tagged human SK1 assessed as production of [32P]-S1P using sphingosine as substrate at 10 uM by TLC method in presence of 100 uM [gamma32P]-ATP relative to control | 2016 | Journal of medicinal chemistry, Feb-11, Volume: 59, Issue:3 | From Sphingosine Kinase to Dihydroceramide Desaturase: A Structure-Activity Relationship (SAR) Study of the Enzyme Inhibitory and Anticancer Activity of 4-((4-(4-Chlorophenyl)thiazol-2-yl)amino)phenol (SKI-II). |
| AID1277483 | Inhibition of recombinant human SK2 assessed as production of [32P] S1P using 10 uM sphingosine as substrate by TLC method in presence of 100 uM [gamma32P]-ATP relative to control | 2016 | Journal of medicinal chemistry, Feb-11, Volume: 59, Issue:3 | From Sphingosine Kinase to Dihydroceramide Desaturase: A Structure-Activity Relationship (SAR) Study of the Enzyme Inhibitory and Anticancer Activity of 4-((4-(4-Chlorophenyl)thiazol-2-yl)amino)phenol (SKI-II). |
| AID1077886 | Decrease of SK1 expression in human PAMSC cells at 100 nM after 24 hrs by Western blot analysis | 2013 | MedChemComm, , Volume: 4, Issue:10 | Novel sphingosine-containing analogues selectively inhibit sphingosine kinase (SK) isozymes, induce SK1 proteasomal degradation and reduce DNA synthesis in human pulmonary arterial smooth muscle cells. |
| AID1908785 | Induction of apoptosis in human MDA-MB-231 cells assessed as early apoptotic cells at 30 uM incubated for 48 hrs by Annexin V-FITC/PI staining based flow cytometry (Rvb = 2.35 %) | |||
| AID1077891 | Inhibition of recombinant SK1 (unknown origin) using sphingosine and [gamma-32P]ATP as substrate after 30 mins | 2013 | MedChemComm, , Volume: 4, Issue:10 | Novel sphingosine-containing analogues selectively inhibit sphingosine kinase (SK) isozymes, induce SK1 proteasomal degradation and reduce DNA synthesis in human pulmonary arterial smooth muscle cells. |
| AID1908736 | Induction of apoptosis in human HT-29 cells assessed as increase in caspase 8 cleavage at 10 uM measured after 48 hrs by western blot analysis | |||
| AID1405277 | Binding affinity to SK1 (unknown origin) assessed as inhibition of sphingosine phosphorylation | 2018 | Journal of medicinal chemistry, 11-21, Volume: 61, Issue:22 | Fibrogenic Disorders in Human Diseases: From Inflammation to Organ Dysfunction. |
| AID1908740 | Induction of apoptosis in human MDA-MB-231 cells assessed as viable cells at 30 uM incubated for 48 hrs by Annexin V-FITC/PI staining based flow cytometry (Rvb = 94.3 %) | |||
| AID1655705 | Inhibition of TGFbeta1-induced fibrosis in mouse C2C12 cells assessed as reduction in alphaSMA protein expression level at 10 uM preincubated for 30 mins followed by TGFbeta1 addition and measured after 48 hrs by Western blot analysis | 2020 | ACS medicinal chemistry letters, May-14, Volume: 11, Issue:5 | Glycans Meet Sphingolipids: Structure-Based Design of Glycan Containing Analogues of a Sphingosine Kinase Inhibitor. |
| AID1908712 | Inhibition of FGFR4 (unknown origin) | |||
| AID1908787 | Induction of apoptosis in human MDA-MB-231 cells assessed as necrotic cells at 30 uM incubated for 48 hrs by Annexin V-FITC/PI staining based flow cytometry (Rvb = 1.42 %) | |||
| AID1694028 | Selectivity ratio of Ki for recombinant human SphK2 assessed as decrease in [33P]SIP production using sphingosine as substrate in presence of [gamma33P]-ATP by scintillation counting method to Ki for recombinant human SphK1 expressed in baculovirus infect | 2021 | Bioorganic & medicinal chemistry, 01-15, Volume: 30 | Lipophilic tail modifications of 2-(hydroxymethyl)pyrrolidine scaffold reveal dual sphingosine kinase 1 and 2 inhibitors. |
| AID1908726 | Induction of cell cycle arrest at G0/G1 phase in human HT-29 cells assessed as reduction in cyclinD1 expression at 10 to 30 uM incubated for 24 hrs by Western blot analysis | |||
| AID1908711 | Inhibition of FGFR3 (unknown origin) | |||
| AID1908689 | Inhibition of SPHK2 (unknown origin) using sphingosine-fluorescein as substrate incubated for 1 hr in presence of ATP by mobility shift assay | |||
| AID1908765 | Toxicity in BALB/c mouse xenografted with human MDA-MB-231 cells assessed as change in body weight at 50 mg/kg/day, ip for 3 weeks and measured every 3 days | |||
| AID1908719 | Induction of cell cycle arrest in human HT-29 cells assessed as accumulation at G0/G1 phase at 10 uM incubated for 24 hrs by PI staining based flow cytometry | |||
| AID1908734 | Induction of apoptosis in human HT-29 cells assessed as increase in PARP cleavage at 10 uM measured after 48 hrs by western blot analysis | |||
| AID1908709 | Inhibition of FGFR1 (unknown origin) | |||
| AID1593545 | Inhibition of recombinant human full-length N-terminal His-tagged SK2 expressed in baculovirus infected Sf9 insect cells at 50 uM using Sph as substrate measured after 30 mins in presence of [gamma32P]ATP by Cerenkov counting analysis relative to control | 2019 | Journal of medicinal chemistry, 04-11, Volume: 62, Issue:7 | Topographical Mapping of Isoform-Selectivity Determinants for J-Channel-Binding Inhibitors of Sphingosine Kinases 1 and 2. |
| AID1908690 | Inhibition of SPHK1 (unknown origin) at 10 uM using sphingosine-fluorescein as substrate incubated for 1 hr in presence of ATP by mobility shift assay relative to control | |||
| AID1908771 | Antimetastatic activity against human MDA-MB-231 cells xenografted in BALB/c mouse assessed as inhibition of NF-kappaB p65 phosphorylation at 30 uM incubated for 2 to 12 hrs by Western blot analysis | |||
| AID1442126 | Inhibition of SPHK2 (unknown origin) by FITC-based caliper assay | 2017 | Journal of medicinal chemistry, 03-23, Volume: 60, Issue:6 | Discovery of a Potent and Selective Sphingosine Kinase 1 Inhibitor through the Molecular Combination of Chemotype-Distinct Screening Hits. |
| AID1161110 | Inhibition of human recombinant Sphk1 at 10 uM after 30 mins by ADP2 fluorescence intensity assay | 2014 | Bioorganic & medicinal chemistry, Oct-01, Volume: 22, Issue:19 | Design, synthesis and evaluation of 2-aminothiazole derivatives as sphingosine kinase inhibitors. |
| AID1277481 | Inhibition of SK1 (unknown origin) using 3 uM of sphingosine as substrate | 2016 | Journal of medicinal chemistry, Feb-11, Volume: 59, Issue:3 | From Sphingosine Kinase to Dihydroceramide Desaturase: A Structure-Activity Relationship (SAR) Study of the Enzyme Inhibitory and Anticancer Activity of 4-((4-(4-Chlorophenyl)thiazol-2-yl)amino)phenol (SKI-II). |
| AID1655709 | Inhibition of TGFbeta1-induced fibrosis in mouse C2C12 cells assessed as reduction in alphaSMA protein expression level at 10 uM preincubated for 120 mins followed by TGFbeta1 addition and measured after 48 hrs by DAPI and rhodamine phalloidin staining ba | 2020 | ACS medicinal chemistry letters, May-14, Volume: 11, Issue:5 | Glycans Meet Sphingolipids: Structure-Based Design of Glycan Containing Analogues of a Sphingosine Kinase Inhibitor. |
| AID1908738 | Induction of cell cycle arrest at G0/G1 phase in human MDA-MB-231 cells at 10 uM incubated for 24 hrs by PI staining based flow cytometry | |||
| AID1908701 | Inhibition of ERBB4 (unknown origin) | |||
| AID1908776 | Induction of apoptosis in human MDA-MB-231 cells assessed as late apoptotic cells at 10 uM incubated for 48 hrs by Annexin V-FITC/PI staining based flow cytometry (Rvb = 1.96 %) | |||
| AID1908729 | Induction of apoptosis in human MDA-MB-231 cells assessed as early apoptotic cells at 10 uM incubated for 48 hrs by Annexin V-FITC/PI staining based flow cytometry (Rvb = 2.35 %) | |||
| AID1908705 | Inhibition of EPHB2 (unknown origin) | |||
| AID1908769 | Toxicity in BALB/c mouse xenografted with human MDA-MB-231 cells assessed as body weight change at 100 mg/kg, ip administrated for 28 days | |||
| AID1161111 | Inhibition of human recombinant Sphk2 at 10 uM after 60 mins by ADP2 fluorescence intensity assay | 2014 | Bioorganic & medicinal chemistry, Oct-01, Volume: 22, Issue:19 | Design, synthesis and evaluation of 2-aminothiazole derivatives as sphingosine kinase inhibitors. |
| AID1277482 | Inhibition of recombinant His-tagged human SK1 assessed as production of [32P]-S1P using 10 uM sphingosine as substrate by TLC method in presence of 100 uM [gamma32P]-ATP | 2016 | Journal of medicinal chemistry, Feb-11, Volume: 59, Issue:3 | From Sphingosine Kinase to Dihydroceramide Desaturase: A Structure-Activity Relationship (SAR) Study of the Enzyme Inhibitory and Anticancer Activity of 4-((4-(4-Chlorophenyl)thiazol-2-yl)amino)phenol (SKI-II). |
| AID1077894 | Inhibition of purified SK2 (unknown origin) using sphingosine and [gamma-32P]ATP as substrate at 50 uM after 30 mins relative to control | 2013 | MedChemComm, , Volume: 4, Issue:10 | Novel sphingosine-containing analogues selectively inhibit sphingosine kinase (SK) isozymes, induce SK1 proteasomal degradation and reduce DNA synthesis in human pulmonary arterial smooth muscle cells. |
| AID1478824 | Inhibition of recombinant C-terminal His6-tagged human SphK1 expressed in baculovirus infected sf21 cells using FITC-sphingosine as substrate after 1 hr in presence of ATP by microfluidic capillary electrophoresis mobility shift assay | 2017 | Bioorganic & medicinal chemistry, 06-15, Volume: 25, Issue:12 | Identification of selective inhibitors of sphingosine kinases 1 and 2 through a structure-activity relationship study of 4-epi-jaspine B. |
| AID1501055 | Inhibition of human C-terminal His6-tagged SphK1 expressed in baculovirus infected Sf21 insect cells | 2017 | European journal of medicinal chemistry, Oct-20, Volume: 139 | An integrative study to identify novel scaffolds for sphingosine kinase 1 inhibitors. |
| AID1908777 | Inhibition of C-terminal His6-tagged human SPHK1 expressed in baculovirus infected Sf21 insect cells using FITC-sphingosine as substrate preincubated for 90 mins followed by substrate addition in presence of ATP by caliper mobility shift assay | |||
| AID1077880 | Inhibition of DNA synthesis in human PAMSC cells assessed as [3H]-thymidine incorporation into DNA at 10 to 100 nM after 24 hrs | 2013 | MedChemComm, , Volume: 4, Issue:10 | Novel sphingosine-containing analogues selectively inhibit sphingosine kinase (SK) isozymes, induce SK1 proteasomal degradation and reduce DNA synthesis in human pulmonary arterial smooth muscle cells. |
| AID1908750 | AUClast in mouse at 20 mg/kg, po | |||
| AID1478825 | Inhibition of human recombinant C-terminal His6 tagged SphK2 expressed in baculovirus infected sf21 cells using FITC-sphingosine as substrate after 1 hr in presence of ATP by microfluidic capillary electrophoresis mobility shift assay | 2017 | Bioorganic & medicinal chemistry, 06-15, Volume: 25, Issue:12 | Identification of selective inhibitors of sphingosine kinases 1 and 2 through a structure-activity relationship study of 4-epi-jaspine B. |
| AID1277462 | Inhibition of SK2 (unknown origin) | 2016 | Journal of medicinal chemistry, Feb-11, Volume: 59, Issue:3 | From Sphingosine Kinase to Dihydroceramide Desaturase: A Structure-Activity Relationship (SAR) Study of the Enzyme Inhibitory and Anticancer Activity of 4-((4-(4-Chlorophenyl)thiazol-2-yl)amino)phenol (SKI-II). |
| AID1908687 | Antimetastatic activity against human MDA-MB-231 cells xenografted in BALB/c mouse assessed as downregulation of MMP-9 at 30 uM incubated for 2 to 12 hrs by western blot analysis | |||
| AID1908691 | Inhibition of SPHK1 (unknown origin) using sphingosine-fluorescein as substrate incubated for 1 hr in presence of ATP by mobility shift assay | |||
| AID1908692 | Inhibition of VEGFR1 (unknown origin) | |||
| AID1694026 | Inhibition of recombinant human SphK1 expressed in baculovirus infected Sf9 cells assessed as decrease in [33P]SIP production using D-erythro-sphingosine as substrate in presence of [gamma33P]-ATP by scintillation counting method | 2021 | Bioorganic & medicinal chemistry, 01-15, Volume: 30 | Lipophilic tail modifications of 2-(hydroxymethyl)pyrrolidine scaffold reveal dual sphingosine kinase 1 and 2 inhibitors. |
| AID1908725 | Induction of cell cycle arrest at G0/G1 phase in human HT-29 cells assessed as reduction in cyclinE1 expression at 10 to 30 uM incubated for 24 hrs by Western blot analysis | |||
| AID1908707 | Inhibition of IGF1R (unknown origin) | |||
| AID1908763 | Toxicity in BALB/c mouse xenografted with human HT-29 cells assessed as change in body weight at 50 mg/kg/day, ip for 3 weeks and measured every 3 days | |||
| AID1908695 | Inhibition of PDGFRalpha (unknown origin) | |||
| AID1908724 | Induction of cell cycle arrest at G0/G1 phase in human HT-29 cells assessed as reduction in cyclinA expression at 10 to 30 uM incubated for 24 hrs by Western blot analysis | |||
| AID1908702 | Inhibition of SRC (unknown origin) | |||
| AID1908755 | Half life in mouse at 2 mg/kg, iv | |||
| AID1077887 | Inhibition of purified SK2 (unknown origin) using sphingosine and [gamma-32P]ATP as substrate at 5 uM after 30 mins relative to control | 2013 | MedChemComm, , Volume: 4, Issue:10 | Novel sphingosine-containing analogues selectively inhibit sphingosine kinase (SK) isozymes, induce SK1 proteasomal degradation and reduce DNA synthesis in human pulmonary arterial smooth muscle cells. |
| AID1908773 | Antimetastatic activity against human MDA-MB-231 cells xenografted in BALB/c mouse assessed as upregulation of phosphorylated beta-catenin at 30 uM incubated for 2 to 12 hrs by western blot analysis | |||
| AID1718951 | Inhibition of SphK2 (unknown origin) | 2021 | Bioorganic & medicinal chemistry letters, 02-15, Volume: 34 | Evaluation of pyrrolidine-based analog of jaspine B as potential SphK1 inhibitors against rheumatoid arthritis. |
| AID1442134 | Inhibition of SPHK1 in human whole-blood using C17-sphingosine as substrate assessed as reduction in C17-S1P production preincubated for 30 mins followed by substrate addition measured after 10 mins by MS analysis | 2017 | Journal of medicinal chemistry, 03-23, Volume: 60, Issue:6 | Discovery of a Potent and Selective Sphingosine Kinase 1 Inhibitor through the Molecular Combination of Chemotype-Distinct Screening Hits. |
| AID1077885 | Decrease of SK1 expression in human PAMSC cells at 100 nM after 24 hrs by Western blot analysis in presence of proteasomal inhibitor MG132 | 2013 | MedChemComm, , Volume: 4, Issue:10 | Novel sphingosine-containing analogues selectively inhibit sphingosine kinase (SK) isozymes, induce SK1 proteasomal degradation and reduce DNA synthesis in human pulmonary arterial smooth muscle cells. |
| AID1478834 | Selectivity ratio of IC50 for human recombinant C-terminal His6 tagged SphK2 expressed in baculovirus infected sf21 cells to IC50 for recombinant C-terminal His6-tagged human SphK1 expressed in baculovirus infected sf21 cells | 2017 | Bioorganic & medicinal chemistry, 06-15, Volume: 25, Issue:12 | Identification of selective inhibitors of sphingosine kinases 1 and 2 through a structure-activity relationship study of 4-epi-jaspine B. |
| AID1908714 | Inhibition of CSF1R (unknown origin) | |||
| AID1908722 | Induction of cell cycle arrest at G0/G1 phase in human HT-29 cells assessed as decrease in p-Rb expression at 10 to 30 uM incubated for 24 hrs by Western blot analysis | |||
| AID1304649 | Inhibition of SphK1 in mouse erythrocytes using sphingosine as substrate by luminescence assay | 2016 | ACS medicinal chemistry letters, Mar-10, Volume: 7, Issue:3 | Structure-Activity Relationship Studies and Molecular Modeling of Naphthalene-Based Sphingosine Kinase 2 Inhibitors. |
| AID1908751 | AUClast in mouse at 2 mg/kg, iv | |||
| AID1908754 | Half life in mouse at 20 mg/kg, po | |||
| AID1908710 | Inhibition of FGFR2 (unknown origin) | |||
| AID1176726 | Selectivity ratio of Ki for Sphk2 (unknown origin) to Ki for His6 tagged human SphK1 expressed in Sf21 cells | 2014 | ACS medicinal chemistry letters, Dec-11, Volume: 5, Issue:12 | Crystal Structure of Sphingosine Kinase 1 with PF-543. |
| AID1908694 | Inhibition of VEGFR3 (unknown origin) | |||
| AID1908723 | Induction of cell cycle arrest at G1 phase in human HT-29 cells assessed as increase in P21 expression at 10 uM incubated for 24 hrs by Western blot analysis | |||
| AID1908696 | Inhibition of PDGFRbeta (unknown origin) | |||
| AID1304653 | Inhibition of human recombinant SphK1 at 0.3 to 3 uM using sphingosine as substrate incubated for 20 mins by scintillation counting analysis in presence of [gamma-32P]ATP | 2016 | ACS medicinal chemistry letters, Mar-10, Volume: 7, Issue:3 | Structure-Activity Relationship Studies and Molecular Modeling of Naphthalene-Based Sphingosine Kinase 2 Inhibitors. |
| AID1908728 | Induction of apoptosis in human HT-29 cells at 10 uM incubated for 48 hrs by Annexin V-FITC/PI staining based flow cytometry | |||
| AID1908772 | Antimetastatic activity against human MDA-MB-231 cells xenografted in BALB/c mouse assessed as inhibition of FSCN1 phosphorylation at 30 uM incubated for 2 to 12 hrs by western blot analysis | |||
| AID1908747 | Cmax in mouse at 20 mg/kg, po | |||
| AID1277465 | Antiproliferative activity against human PC3 cells after 72 hrs by MTS assay | 2016 | Journal of medicinal chemistry, Feb-11, Volume: 59, Issue:3 | From Sphingosine Kinase to Dihydroceramide Desaturase: A Structure-Activity Relationship (SAR) Study of the Enzyme Inhibitory and Anticancer Activity of 4-((4-(4-Chlorophenyl)thiazol-2-yl)amino)phenol (SKI-II). |
| AID1277461 | Inhibition of SK1 (unknown origin) | 2016 | Journal of medicinal chemistry, Feb-11, Volume: 59, Issue:3 | From Sphingosine Kinase to Dihydroceramide Desaturase: A Structure-Activity Relationship (SAR) Study of the Enzyme Inhibitory and Anticancer Activity of 4-((4-(4-Chlorophenyl)thiazol-2-yl)amino)phenol (SKI-II). |
| AID1908717 | Antiproliferative activity against human HT-29 cells incubated for 72 hrs by SRB assay | |||
| AID1908760 | Oral bioavailability in in mouse at 20 mg/kg | |||
| AID1908700 | Inhibition of ERBB2 (unknown origin) | |||
| AID1908721 | Induction of cell cycle arrest at G1 phase in human HT-29 cells assessed as increase in P21 expression at 30 uM incubated for 24 hrs by Western blot analysis | |||
| AID1277480 | Inhibition of SK1 (unknown origin) using 5 uM of sphingosine as substrate | 2016 | Journal of medicinal chemistry, Feb-11, Volume: 59, Issue:3 | From Sphingosine Kinase to Dihydroceramide Desaturase: A Structure-Activity Relationship (SAR) Study of the Enzyme Inhibitory and Anticancer Activity of 4-((4-(4-Chlorophenyl)thiazol-2-yl)amino)phenol (SKI-II). |
| AID1482728 | Inhibition of recombinant human C-terminal His-tagged SPHK1 expressed in fall armyworm sf21 cells using sphingosine as substrate after 1 hr by FITC-based caliper assay | |||
| AID1908784 | Half life in mouse at 10 mg/kg, ip | |||
| AID1442135 | Selectivity ratio of IC50 for SPHK2 (unknown origin) to IC50 for human C-terminal His6-tagged SPHK1 expressed in fall armyworm sf9 cells | 2017 | Journal of medicinal chemistry, 03-23, Volume: 60, Issue:6 | Discovery of a Potent and Selective Sphingosine Kinase 1 Inhibitor through the Molecular Combination of Chemotype-Distinct Screening Hits. |
| AID1705514 | Competitive inhibition of recombinant human C-terminal His-tagged SphK1 expressed in baculovirus infected Sf21 cells using varying concentrations of FITC-sphingosine as substrate incubated for 30 mins by LC-MS/MS analysis | 2020 | European journal of medicinal chemistry, Nov-15, Volume: 206 | Structure-activity relationship studies and bioactivity evaluation of 1,2,3-triazole containing analogues as a selective sphingosine kinase-2 inhibitors. |
| AID1908741 | Antimigratory activity against human MDA-MB-231 cells assessed as reduction in cell migration at 40 uM incubated for 8 hrs by crystal violet staining microscopy based transwell migration assay | |||
| AID1718950 | Inhibition of SphK1 (unknown origin) | 2021 | Bioorganic & medicinal chemistry letters, 02-15, Volume: 34 | Evaluation of pyrrolidine-based analog of jaspine B as potential SphK1 inhibitors against rheumatoid arthritis. |
| AID1304650 | Selectivity ratio of Ki for SphK2 in mouse erythrocytes to Ki for SphK1 in mouse erythrocytes | 2016 | ACS medicinal chemistry letters, Mar-10, Volume: 7, Issue:3 | Structure-Activity Relationship Studies and Molecular Modeling of Naphthalene-Based Sphingosine Kinase 2 Inhibitors. |
| AID1908786 | Induction of apoptosis in human MDA-MB-231 cells assessed as late apoptotic cells at 30 uM incubated for 48 hrs by Annexin V-FITC/PI staining based flow cytometry (Rvb = 1.96 %) | |||
| AID1908739 | Induction of apoptosis in human MDA-MB-231 cells assessed as viable cells at 10 uM incubated for 48 hrs by Annexin V-FITC/PI staining based flow cytometry (Rvb = 94.3 %) | |||
| AID1655706 | Inhibition of TGFbeta1-induced fibrosis in mouse C2C12 cells assessed as reduction in SMalpha22 protein expression level at 10 uM preincubated for 30 mins followed by TGFbeta1 addition and measured after 48 hrs by Western blot analysis | 2020 | ACS medicinal chemistry letters, May-14, Volume: 11, Issue:5 | Glycans Meet Sphingolipids: Structure-Based Design of Glycan Containing Analogues of a Sphingosine Kinase Inhibitor. |
| AID1199975 | Inhibition of human recombinant SphK1 expressed in Sf9 cells assessed as radiolabeled products using 5 uM sphingosine and 10 uM gamma[32P]ATP by liquid scintillation counting | 2015 | Journal of medicinal chemistry, Feb-26, Volume: 58, Issue:4 | Structure-activity relationship studies and in vivo activity of guanidine-based sphingosine kinase inhibitors: discovery of SphK1- and SphK2-selective inhibitors. |
| 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. |
| AID1345886 | Human sphingosine kinase 1 (Sphingosine kinase) | 2012 | The Biochemical journal, May-15, Volume: 444, Issue:1 | Modulation of cellular S1P levels with a novel, potent and specific inhibitor of sphingosine kinase-1. |
| [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 | 0 (0.00) | 29.6817 |
| 2010's | 28 (51.85) | 24.3611 |
| 2020's | 26 (48.15) | 2.80 |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||
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 (34.19) All Compounds (24.57) |
| Publication Type | This drug (%) | All Drugs (%) |
|---|---|---|
| Trials | 0 (0.00%) | 5.53% |
| Reviews | 3 (5.56%) | 6.00% |
| Case Studies | 0 (0.00%) | 4.05% |
| Observational | 0 (0.00%) | 0.25% |
| Other | 51 (94.44%) | 84.16% |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||