Drug Information

Drug (ID: DG01661) and It's Reported Resistant Information

• Name: SEL201
• Synonyms: SLV-2436; 2095704-43-9; SEL-201; CID 129052025; CHEMBL4764756; 5-(3-Amino-1H-indazol-6-yl)-1-[(3-chlorophenyl)methyl]pyridin-2-one; SEL201; SCHEMBL18764462; SLV2436; BCP29427; SLV 2436; VID70443; BDBM50562615; s6888; SEL201-88; BS-15825; HY-112113; CS-0043363; D80426; 5-(3-amino-1H-indazol-6-yl)-1-(3-chlorobenzyl)pyridin-2(1H)-one; SLV 2436 pound>>SLV2436 pound>>SEL201-88; SEL-201 pound>>SEL201 88; SEL 201 pound>>SEL20188; SEL201
• Target: .; NOUNIPROTAC; [1]
• Formula: 3
• IsoSMILES: C1=CC(=CC(=C1)Cl)CN2C=C(C=CC2=O)C3=CC4=C(C=C3)C(=NN4)N
• InChI: InChI=1S/C19H15ClN4O/c20-15-3-1-2-12(8-15)10-24-11-14(5-7-18(24)25)13-4-6-16-17(9-13)22-23-19(16)21/h1-9,11H,10H2,(H3,21,22,23)
• InChIKey: YQVUADHJKWJHAF-UHFFFAOYSA-N
• PubChem CID: 129052025

Type(s) of Resistant Mechanism of This Drug

  EADR: Epigenetic Alteration of DNA, RNA or Protein

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

Melanoma [ICD-11: 2C30]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [1]

• Molecule Alteration: Missense mutation; p.L576P (c.1727T>C)
• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: MM61 cells; N.A.; .; N.A.
• In Vitro Model: MM111 cells; N.A.; .; N.A.
• In Vitro Model: M230 cells; Skin; Homo sapiens (Human); CVCL_D749
• In Vitro Model: LND1 cells; Skin; Homo sapiens (Human); CVCL_J076
• In Vitro Model: HBL cells; Skin; Homo sapiens (Human); CVCL_J075
• In Vivo Model: CD-1 mouse PDX model; Mus musculus
• Experiment for Drug Resistance: SRB assay; Crystal violet staining assay; Promega assay
• Mechanism Description: c-KIT stimulates MAP kinase-interacting serine/threonine kinases 1 and 2 (MNK1/2), which phosphorylate eukaryotic translation initiation factor 4E (eIF4E) and render it oncogenic. Depletion of MNK1/2 in melanoma cells with oncogenic C-KIT inhibited cell migration and mRNA translation of the transcriptional repressor SNAI1 and the cell cycle gene CCNE1. This suggested that blocking MNK1/2 activity may inhibit tumor progression, at least in part, by blocking translation initiation of mRNAs encoding cell migration proteins.

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [1]

• Molecule Alteration: Missense mutation; p.D820Y (c.2458G>T)
• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: MM61 cells; N.A.; .; N.A.
• In Vitro Model: MM111 cells; N.A.; .; N.A.
• In Vitro Model: M230 cells; Skin; Homo sapiens (Human); CVCL_D749
• In Vitro Model: LND1 cells; Skin; Homo sapiens (Human); CVCL_J076
• In Vitro Model: HBL cells; Skin; Homo sapiens (Human); CVCL_J075
• In Vivo Model: CD-1 mouse PDX model; Mus musculus
• Experiment for Drug Resistance: SRB assay; Crystal violet staining assay; Promega assay
• Mechanism Description: c-KIT stimulates MAP kinase-interacting serine/threonine kinases 1 and 2 (MNK1/2), which phosphorylate eukaryotic translation initiation factor 4E (eIF4E) and render it oncogenic. Depletion of MNK1/2 in melanoma cells with oncogenic C-KIT inhibited cell migration and mRNA translation of the transcriptional repressor SNAI1 and the cell cycle gene CCNE1. This suggested that blocking MNK1/2 activity may inhibit tumor progression, at least in part, by blocking translation initiation of mRNAs encoding cell migration proteins.

References

• Ref 1: MNK1/2 inhibition limits oncogenicity and metastasis of KIT-mutant melanomaJ Clin Invest. 2017 Nov 1;127(11):4179-4192. doi: 10.1172/JCI91258. Epub 2017 Oct 16.