Drug Information

Drug (ID: DG01590) and It's Reported Resistant Information

• Name: VE-821
• Synonyms: VE-821; 1232410-49-9; 3-Amino-6-(4-(methylsulfonyl)phenyl)-N-phenylpyrazine-2-carboxamide; VE 821; VE821; 3-Amino-6-[4-(methylsulfonyl)phenyl]-N-phenyl-2-pyrazinecarboxamide; UNII-BF884TQ935; CHEMBL1766779; 3-amino-6-(4-methylsulfonylphenyl)-N-phenylpyrazine-2-carboxamide; BF884TQ935; 3-AMINO-6-(4-METHANESULFONYLPHENYL)-N-PHENYLPYRAZINE-2-CARBOXAMIDE; 3-Amino-6-(4-(methylsulfonyl)phenyl)-N-phenyl-2-pyrazinecarboxamide; 2-Pyrazinecarboxamide, 3-amino-6-(4-(methylsulfonyl)phenyl)-N-phenyl-; 2-Pyrazinecarboxamide, 3-amino-6-[4-(methylsulfonyl)phenyl]-N-phenyl-; ATR Inhibitor IV; MLS006011215; GTPL8042; SCHEMBL2483543; DTXSID60679574; EX-A530; CHEBI:124916; HMS3653B19; HMS3673C07; HMS3744G05; BCP02617; 2788AH; BDBM50341733; MFCD19443686; NSC761070; s8007; ZINC68244543; AKOS025212610; CCG-268268; CS-0238; NSC-761070; SB19277; NCGC00346444-01; NCGC00346444-07; AC-30933; AS-72494; BV168070; HY-14731; SMR004702977; VE-821, >=98% (HPLC); FT-0700135; SW219507-1; J-690084; Q27089128; 3-Amino-6-[4-(methlsulfonyl)phenyl)-N-phenyl-2-pyrazinecarboxamide; 3-Azanyl-6-(4-methylsulfonylphenyl)-N-phenyl-pyrazine-2-carboxamide; 3-amino-6-(4-(methyl sulfonyl)phenyl)-n-phenyl-2-pyrazinecarboxamide; 3-Amino-6-[4-(methanesulfonyl)phenyl]-N-phenylpyrazine-2-carboxamide
• Indication:
  In total 1 Indication(s)
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; Phase 1; [1]
• Target: Serine/threonine-protein kinase ATR (FRP1); ATR_HUMAN; [1]
• Formula: 4
• IsoSMILES: CS(=O)(=O)C1=CC=C(C=C1)C2=CN=C(C(=N2)C(=O)NC3=CC=CC=C3)N
• InChI: InChI=1S/C18H16N4O3S/c1-26(24,25)14-9-7-12(8-10-14)15-11-20-17(19)16(22-15)18(23)21-13-5-3-2-4-6-13/h2-11H,1H3,(H2,19,20)(H,21,23)
• InChIKey: DUIHHZKTCSNTGM-UHFFFAOYSA-N
• PubChem CID: 51000408
• ChEBI ID: CHEBI:124916

Type(s) of Resistant Mechanism of This Drug

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

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

Colorectal cancer [ICD-11: 2B91]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: AT-rich interactive domain-containing protein 1A (ARID1A) [1]

• Molecule Alteration: Nonsense; p.Q456* (c.1366C>T)
• Sensitive Disease: Colorectal cancer [ICD-11: 2B91.1]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: ES2 cells; Ovary; Homo sapiens (Human); CVCL_AX39
• In Vitro Model: TOV21G cells; Ovary; Homo sapiens (Human); CVCL_3613
• In Vitro Model: SMOV2 cells; Ovary; Homo sapiens (Human); CVCL_S920
• In Vitro Model: RMG-1 cells; Ascites; Homo sapiens (Human); CVCL_1662
• In Vitro Model: OVTOKO cells; Spleen; Homo sapiens (Human); CVCL_3117
• In Vitro Model: OVSAYO cells; Ovary; Homo sapiens (Human); CVCL_3115
• In Vitro Model: OVMANA cells; Ovary; Homo sapiens (Human); CVCL_3111
• In Vitro Model: OVISE cells; Pelvi; Homo sapiens (Human); CVCL_3116
• In Vitro Model: OVAS cells; Ascites; Homo sapiens (Human); CVCL_0V12
• In Vitro Model: KOC7C cells; Pleural effusion; Homo sapiens (Human); CVCL_5307
• In Vitro Model: KK cells; Ascites; Homo sapiens (Human); CVCL_F844
• In Vitro Model: HCH1 cells; Ovary; Homo sapiens (Human); CVCL_DF05
• In Vivo Model: CD-1 Nude mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: ApoTox-Glo triplex assay
• Mechanism Description: Defects in ARID1A sensitize tumour cells to clinical inhibitors of the DNA damage checkpoint kinase, ATR, both in vitro and in vivo. Mechanistically, ARID1A deficiency results in topoisomerase 2A and cell cycle defects, which cause an increased reliance on ATR checkpoint activity. In ARID1A mutant tumour cells, inhibition of ATR triggers premature mitotic entry, genomic instability and apoptosis.

References

• Ref 1: ATR inhibitors as a synthetic lethal therapy for tumours deficient in ARID1ANat Commun. 2016 Dec 13;7:13837. doi: 10.1038/ncomms13837.