dwb2023/gtopdb-target-family-interaction-detail huggingface dataset:
Target family: STE7 family (type: enzyme)
Target: mitogen-activated protein kinase kinase 1

Ligand: nedometinib (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 6.610000133514404 pIC50
Reference (Patent): Pyrrolopyridine-aniline compounds for treatment of dermal disorders

Ligand: refametinib (Synthetic organic)
Interaction type: Allosteric modulator
Action: Negative
Ligand approved: no
Primary target: yes
Median affinity: 7.71999979019165 pIC50
Reference (Journal): RDEA119/BAY 869766: a potent, selective, allosteric inhibitor of MEK1/2 for the treatment of cancer.
Published in: Cancer Res

Ligand: selumetinib (Synthetic organic)
Interaction type: Allosteric modulator
Action: Negative
Ligand approved: yes
Approval source: FDA (2020)
Primary target: yes
Median affinity:  pIC50
Reference (Journal): Biological characterization of ARRY-142886 (AZD6244), a potent, highly selective mitogen-activated protein kinase kinase 1/2 inhibitor.
Published in: Clin Cancer Res

Ligand: selumetinib (Synthetic organic)
Interaction type: Allosteric modulator
Action: Negative
Ligand approved: yes
Approval source: FDA (2020)
Primary target: yes
Median affinity:  pIC50
Reference (Journal): Targeted inhibition of the extracellular signal-regulated kinase kinase pathway with AZD6244 (ARRY-142886) in the treatment of hepatocellular carcinoma.
Published in: Mol Cancer Ther

Ligand: TAK-733 (Synthetic organic)
Interaction type: Allosteric modulator
Action: Inhibition
Ligand approved: no
Primary target: yes
Median affinity: 8.489999771118164 pIC50
Reference (Journal): Discovery of TAK-733, a potent and selective MEK allosteric site inhibitor for the treatment of cancer.
Published in: Bioorg Med Chem Lett

Ligand: trametinib (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: FDA (2013), EMA (2014)
Primary target: yes
Median affinity:  pIC50
Reference (Journal): Antitumor activities of JTP-74057 (GSK1120212), a novel MEK1/2 inhibitor, on colorectal cancer cell lines in vitro and in vivo.
Published in: Int J Oncol

Ligand: trametinib (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: FDA (2013), EMA (2014)
Primary target: yes
Median affinity:  pIC50
Reference (Journal): GSK1120212 (JTP-74057) is an inhibitor of MEK activity and activation with favorable pharmacokinetic properties for sustained in vivo pathway inhibition.
Published in: Clin Cancer Res

Ligand: zapnometinib (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 8.239999771118164 pIC50
Reference (Journal): Beyond the MEK-pocket: can current MEK kinase inhibitors be utilized to synthesize novel type III NCKIs? Does the MEK-pocket exist in kinases other than MEK?
Published in: Bioorg Med Chem Lett
Target family: STE7 family (type: enzyme)
Target: mitogen-activated protein kinase kinase 2

Ligand: BI-847325 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 8.399999618530273 pIC50
Reference (Journal): Pharmacological Profile of BI 847325, an Orally Bioavailable, ATP-Competitive Inhibitor of MEK and Aurora Kinases.
Published in: Mol Cancer Ther

Ligand: binimetinib (Synthetic organic)
Interaction type: Allosteric modulator
Action: Negative
Ligand approved: yes
Approval source: FDA and EMA (2018)
Primary target: yes
Median affinity: 7.920000076293945 pIC50
Reference (Journal): Characterization of ARRY-438162, a Potent MEK Inhibitor in Combination with Methotrexate or Ibuprofen in In Vivo Models of Arthritis.[abstract].
Published in: American College of Rheumatology 2006 Annual Scientific Meeting

Ligand: cobimetinib (Synthetic organic)
Interaction type: Allosteric modulator
Action: Negative
Ligand approved: yes
Approval source: FDA & EMA (2015)
Primary target: yes
Median affinity: 6.699999809265137 pIC50
Reference (Journal): Novel Carboxamide-Based Allosteric MEK Inhibitors: Discovery and Optimization Efforts toward XL518 (GDC-0973).
Published in: ACS Med Chem Lett

Ligand: MEK1/2 inhibitor (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: yes
Median affinity: 6.659999847412109 pIC50
Reference (Journal): A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases.
Published in: Proc Natl Acad Sci USA

Ligand: MS432 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 6.230000019073486 pIC50
Reference (Journal): Discovery of a First-in-Class Mitogen-Activated Protein Kinase Kinase 1/2 Degrader.
Published in: J Med Chem

Ligand: refametinib (Synthetic organic)
Interaction type: Allosteric modulator
Action: Negative
Ligand approved: no
Primary target: yes
Median affinity: 7.329999923706055 pIC50
Reference (Journal): RDEA119/BAY 869766: a potent, selective, allosteric inhibitor of MEK1/2 for the treatment of cancer.
Published in: Cancer Res

Ligand: trametinib (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: FDA (2013), EMA (2014)
Primary target: yes
Median affinity: 8.739999771118164 pIC50
Reference (Journal): Antitumor activities of JTP-74057 (GSK1120212), a novel MEK1/2 inhibitor, on colorectal cancer cell lines in vitro and in vivo.
Published in: Int J Oncol

Ligand: voruciclib (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 7.059999942779541 pIC50
Reference (Journal): Cyclin-Dependent Kinase Inhibitor P1446A Induces Apoptosis in a JNK/p38 MAPK-Dependent Manner in Chronic Lymphocytic Leukemia B-Cells.
Published in: PLoS ONE
Target family: STE7 family (type: enzyme)
Target: mitogen-activated protein kinase kinase 3

Ligand: MEK inhibitor I (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 6 pIC50
Reference (Journal): Beyond U0126. Dianion chemistry leading to the rapid synthesis of a series of potent MEK inhibitors.
Published in: Bioorg Med Chem Lett

Ligand: (R)-STU104 (Synthetic organic)
Interaction type: None
Action: Binding
Ligand approved: no
Primary target: no
Median affinity: 7.150000095367432 pKi
Reference (Journal): Discovery of First-in-Class TAK1-MKK3 Protein-Protein Interaction (PPI) Inhibitor <b>(<i>R</i>)-STU104</b> for the Treatment of Ulcerative Colitis through Modulating TNF-α Production.
Published in: J Med Chem
Target family: STE7 family (type: enzyme)
Target: mitogen-activated protein kinase kinase 4

Ligand: compound 11 [PMID: 26431428] (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 5.300000190734863 pIC50
Reference (Journal): Biological profile of L-745,870, a selective antagonist with high affinity for the dopamine D4 receptor.
Published in: J Pharmacol Exp Ther

Ligand: darizmetinib (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 6.300000190734863 pIC50
Reference (Patent): Protein kinase mkk4 inhibitors for promoting liver regeneration or reducing or preventing hepatocyte death

Ligand: MEK inhibitor I (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 6 pIC50
Reference (Journal): Beyond U0126. Dianion chemistry leading to the rapid synthesis of a series of potent MEK inhibitors.
Published in: Bioorg Med Chem Lett

Ligand: staurosporine (Natural product)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 9 pIC50
Reference (Journal): Identification of orally active, potent, and selective 4-piperazinylquinazolines as antagonists of the platelet-derived growth factor receptor tyrosine kinase family.
Published in: J Med Chem
Target family: STE7 family (type: enzyme)
Target: mitogen-activated protein kinase kinase 5

Ligand: BIX02188 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: yes
Median affinity: 8.369999885559082 pIC50
Reference (Journal): Identification of pharmacological inhibitors of the MEK5/ERK5 pathway.
Published in: Biochem Biophys Res Commun

Ligand: BIX02189 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: yes
Median affinity: 8.819999694824219 pIC50
Reference (Journal): Identification of pharmacological inhibitors of the MEK5/ERK5 pathway.
Published in: Biochem Biophys Res Commun
Target family: STE7 family (type: enzyme)
Target: mitogen-activated protein kinase kinase 1

Ligand: MEK inhibitor II (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 6.420000076293945 pIC50
Reference (Journal): A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases.
Published in: Proc Natl Acad Sci USA

Ligand: MS432 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 5.820000171661377 pIC50
Reference (Journal): Discovery of a First-in-Class Mitogen-Activated Protein Kinase Kinase 1/2 Degrader.
Published in: J Med Chem
Target family: STE7 family (type: enzyme)
Target: mitogen-activated protein kinase kinase 7

Ligand: compound 11 [PMID: 26431428] (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 5.300000190734863 pIC50
Reference (Journal): Scaffold-Hopping and Structure-Based Discovery of Potent, Selective, And Brain Penetrant N-(1H-Pyrazol-3-yl)pyridin-2-amine Inhibitors of Dual Leucine Zipper Kinase (DLK, MAP3K12).
Published in: J Med Chem

Ligand: cobimetinib (Synthetic organic)
Interaction type: Allosteric modulator
Action: Negative
Ligand approved: yes
Approval source: FDA & EMA (2015)
Primary target: no
Median affinity: 5 pIC50
Reference (Journal): Novel Carboxamide-Based Allosteric MEK Inhibitors: Discovery and Optimization Efforts toward XL518 (GDC-0973).
Published in: ACS Med Chem Lett
Target family: STE7 family (type: enzyme)
Target: mitogen-activated protein kinase kinase 1

Ligand: E6201 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: yes
Median affinity: 8.279999732971191 pIC50
Reference (Journal): E6201 [(3S,4R,5Z,8S,9S,11E)-14-(ethylamino)-8, 9,16-trihydroxy-3,4-dimethyl-3,4,9,19-tetrahydro-1H-2-benzoxacyclotetradecine-1,7(8H)-dione], a novel kinase inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK)-1 and MEK kinase-1: in vitro characterization of its anti-inflammatory and antihyperproliferative activities.
Published in: J Pharmacol Exp Ther

Ligand: compound 3 [PMID: 31804822] (Synthetic organic)
Interaction type: Allosteric modulator
Action: Negative
Ligand approved: no
Primary target: no
Median affinity: 7 pIC50
Reference (Journal): Design, Synthesis, and Biological Evaluation of MEK PROTACs.
Published in: J Med Chem

Ligand: cobimetinib (Synthetic organic)
Interaction type: Allosteric modulator
Action: Negative
Ligand approved: yes
Approval source: FDA & EMA (2015)
Primary target: yes
Median affinity: 9.050000190734863 pIC50
Reference (Journal): Novel Carboxamide-Based Allosteric MEK Inhibitors: Discovery and Optimization Efforts toward XL518 (GDC-0973).
Published in: ACS Med Chem Lett

Ligand: CI-1040 (Synthetic organic)
Interaction type: Allosteric modulator
Action: Negative
Ligand approved: no
Primary target: yes
Median affinity: 6.920000076293945 pKd
Reference (Journal): Comprehensive analysis of kinase inhibitor selectivity.
Published in: Nat Biotechnol

Ligand: CI-1040 (Synthetic organic)
Interaction type: Allosteric modulator
Action: Negative
Ligand approved: no
Primary target: no
Median affinity: 6.519999980926514 pIC50
Reference (Journal): Specificity and mechanism of action of some commonly used protein kinase inhibitors.
Published in: Biochem J

Ligand: CH4987655 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 8.279999732971191 pIC50
Reference (Journal): Design and synthesis of novel allosteric MEK inhibitor CH4987655 as an orally available anticancer agent.
Published in: Bioorg Med Chem Lett
Target family: STE7 family (type: enzyme)
Target: mitogen-activated protein kinase kinase 6

Ligand: staurosporine (Natural product)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 9 pIC50
Reference (Journal): Identification of orally active, potent, and selective 4-piperazinylquinazolines as antagonists of the platelet-derived growth factor receptor tyrosine kinase family.
Published in: J Med Chem
Target family: STE7 family (type: enzyme)
Target: mitogen-activated protein kinase kinase 1

Ligand: binimetinib (Synthetic organic)
Interaction type: Allosteric modulator
Action: Negative
Ligand approved: yes
Approval source: FDA and EMA (2018)
Primary target: yes
Median affinity: 7.920000076293945 pIC50
Reference (Journal): Characterization of ARRY-438162, a Potent MEK Inhibitor in Combination with Methotrexate or Ibuprofen in In Vivo Models of Arthritis.[abstract].
Published in: American College of Rheumatology 2006 Annual Scientific Meeting

Ligand: BI-847325 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 7.599999904632568 pIC50
Reference (Journal): Pharmacological Profile of BI 847325, an Orally Bioavailable, ATP-Competitive Inhibitor of MEK and Aurora Kinases.
Published in: Mol Cancer Ther

Ligand: avutometinib (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 6.800000190734863 pIC50
Reference (Journal): Optimizing the Physicochemical Properties of Raf/MEK Inhibitors by Nitrogen Scanning.
Published in: ACS Med Chem Lett

Ligand: MEK inhibitor I (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: yes
Median affinity: 7.920000076293945 pIC50
Reference (Journal): Beyond U0126. Dianion chemistry leading to the rapid synthesis of a series of potent MEK inhibitors.
Published in: Bioorg Med Chem Lett

Ligand: mirdametinib (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: yes
Median affinity: 8.149999618530273 pIC50
Reference (Journal): Optimization of allosteric MEK inhibitors. Part 1: Venturing into underexplored SAR territories.
Published in: Bioorg Med Chem Lett

Ligand: MAP855 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 8.300000190734863 pIC50
Reference (Journal): Discovery of MAP855, an Efficacious and Selective MEK1/2 Inhibitor with an ATP-Competitive Mode of Action.
Published in: J Med Chem

Ligand: GDC-0623 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 9 pKi
Reference (Journal): Mechanism of MEK inhibition determines efficacy in mutant KRAS- versus BRAF-driven cancers.
Published in: Nature
Target family: STE7 family (type: enzyme)
Target: mitogen-activated protein kinase kinase 7

Ligand: compound 1k [PMID: 35912476] (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 8.399999618530273 pIC50
Reference (Journal): Optimization of Covalent MKK7 Inhibitors <i>via</i> Crude Nanomole-Scale Libraries.
Published in: J Med Chem
Target family: STE-unique family (type: enzyme)
Target: mitogen-activated protein kinase kinase kinase 14

Ligand: AMG28 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 6 pKi
Reference (Patent): Alkynyl alcohols as kinase inhibitors

Ligand: NIK SMI1 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 9.399999618530273 pKi
Reference (Journal): NF-κB inducing kinase is a therapeutic target for systemic lupus erythematosus.
Published in: Nat Commun

Ligand: NIK inhibitor 12f (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 8.010000228881836 pIC50
Reference (Journal): Identification of <i>N</i>-Phenyl-7<i>H</i>-pyrrolo[2,3-<i>d</i>]pyrimidin-4-amine Derivatives as Novel, Potent, and Selective NF-κB Inducing Kinase (NIK) Inhibitors for the Treatment of Psoriasis.
Published in: J Med Chem

Ligand: compound 3a [Pipionne et al, 2018] (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 5.079999923706055 pIC50
Reference (Journal): <i>N</i>-Acetyl-3-aminopyrazoles block the non-canonical NF-kB cascade by selectively inhibiting NIK.
Published in: Medchemcomm

Ligand: compound 31 [PMID: 23374866] (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: yes
Median affinity: 7.699999809265137 pIC50
Reference (Journal): Inhibiting NF-κB-inducing kinase (NIK): discovery, structure-based design, synthesis, structure-activity relationship, and co-crystal structures.
Published in: Bioorg Med Chem Lett

Ligand: compound 18 [PMID: 34212719] (Synthetic organic)
Interaction type: Inhibitor
Action: Irreversible inhibition
Ligand approved: no
Primary target: no
Median affinity: 6.699999809265137 pIC50
Reference (Journal): An Alkynylpyrimidine-Based Covalent Inhibitor That Targets a Unique Cysteine in NF-&#x3ba;B-Inducing Kinase.
Published in: J Med Chem
Target family: STE-unique family (type: enzyme)
Target: mitogen-activated protein kinase kinase kinase 8

Ligand: Tpl2 kinase inhibitor (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: yes
Median affinity: 7.300000190734863 pIC50
Reference (Journal): Inhibition of Tpl2 kinase and TNF-alpha production with 1,7-naphthyridine-3-carbonitriles: synthesis and structure-activity relationships.
Published in: Bioorg Med Chem Lett

Ligand: MEK inhibitor II (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: yes
Median affinity: 7.300000190734863 pIC50
Reference (Journal): A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases.
Published in: Proc Natl Acad Sci USA
Target family: STE-unique family (type: enzyme)
Target: mitogen-activated protein kinase kinase kinase 14

Ligand: NIK SMI1 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: yes
Median affinity: 9.640000343322754 pKi
Reference (Journal): NF-κB inducing kinase is a therapeutic target for systemic lupus erythematosus.
Published in: Nat Commun
Target family: Sugar kinases (type: enzyme)
Target: ketohexokinase

Ligand: LY3522348 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity:  pIC50
Reference (Journal): Identification of LY3522348: A Highly Selective and Orally Efficacious Ketohexokinase Inhibitor.
Published in: J Med Chem

Ligand: LY3522348 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 7.389999866485596 pIC50
Reference (Journal): Identification of LY3522348: A Highly Selective and Orally Efficacious Ketohexokinase Inhibitor.
Published in: J Med Chem

Ligand: PF-06835919 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 8 pIC50
Reference (Journal): Discovery of PF-06835919: A Potent Inhibitor of Ketohexokinase (KHK) for the Treatment of Metabolic Disorders Driven by the Overconsumption of Fructose.
Published in: J Med Chem
Target family: Sugar phosphatases (type: enzyme)
Target: 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3

Ligand: PFKFB3 kinase Inhibitor 69 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 7.849999904632568 pIC50
Reference (Journal): Discovery and Structure-Activity Relationships of N-Aryl 6-Aminoquinoxalines as Potent PFKFB3 Kinase Inhibitors.
Published in: ChemMedChem

Ligand: PFK15 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: yes
Median affinity: 6.679999828338623 pIC50
Reference (Journal): Targeting 6-phosphofructo-2-kinase (PFKFB3) as a therapeutic strategy against cancer.
Published in: Mol Cancer Ther
Target family: Syk family (type: enzyme)
Target: zeta chain of T cell receptor associated protein kinase 70

Ligand: aloisine (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 5.579999923706055 pKi
Reference (Journal): Identification of binding specificity-determining features in protein families.
Published in: J Med Chem

Ligand: mivavotinib (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 7.130000114440918 pIC50
Reference (Journal): Discovery of TAK-659 an orally available investigational inhibitor of Spleen Tyrosine Kinase (SYK).
Published in: Bioorg Med Chem Lett

Ligand: Syk inhibitor II (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 4.949999809265137 pIC50
Reference (Journal): Synthetic studies on novel Syk inhibitors. Part 1: Synthesis and structure-activity relationships of pyrimidine-5-carboxamide derivatives.
Published in: Bioorg Med Chem