Drug Information

Drug (ID: DG01610) and It's Reported Resistant Information

• Name: Berzosertib
• Synonyms: VE-822; 1232416-25-9; Berzosertib; VX-970; VE822; UNII-L423PRV3V3; VE 822; VX970; VE-822 (VX-970); 5-(4-(isopropylsulfonyl)phenyl)-3-(3-(4-((methylamino)methyl)phenyl)isoxazol-5-yl)pyrazin-2-amine; L423PRV3V3; 3-(3-{4-[(METHYLAMINO)METHYL]PHENYL}-1,2-OXAZOL-5-YL)-5-[4-(PROPANE-2-SULFONYL)PHENYL]PYRAZIN-2-AMINE; 3-[3-[4-(methylaminomethyl)phenyl]-1,2-oxazol-5-yl]-5-(4-propan-2-ylsulfonylphenyl)pyrazin-2-amine; M6620; 2-Pyrazinamine, 3-(3-(4-((methylamino)methyl)phenyl)-5-isoxazolyl)-5-(4-((1-methylethyl)sulfonyl)phenyl)-; BDBM50226746; 2-Pyrazinamine, 3-[3-[4-[(methylamino)methyl]phenyl]-5-isoxazolyl]-5-[4-[(1-methylethyl)sulfonyl]phenyl]-; 3-(3-(4-((METHYLAMINO)METHYL)PHENYL)-1,2-OXAZOL-5-YL)-5-(4-(PROPANE-2-SULFONYL)PHENYL)PYRAZIN-2-AMINE; 3-[3-[4-[(Methylamino)methyl]phenyl]-5-isoxazolyl]-5-[4-[(1-methylethyl)sulfonyl]phenyl]-2-pyrazinamine; 5-(4-(isopropylsulfonyl)phenyl)-3-(3-(4-((methylamino)methyl)phenyl)isoxazol-5-yl)pyrazin-2-amine.; Berzosertib [USAN]; VX-970;Berzosertib; Berzosertib (USAN/INN); Berzosertib (VE-822); AGN-PC-0CXKB3; GTPL8003; SCHEMBL3061890; CHEMBL3989870; EX-A529; CHEBI:131166; BDBM350085; HMS3653C05; HMS3747I11; AOB87712; BCP07948; 2789AH; MFCD27976794; NSC777718; s7102; US10208027, Compound II-1; US10208027, Compound II-2; US10208027, Compound II-3; US10208027, Compound II-4; VX 970; ZINC96170459; AKOS025404905; CCG-264673; CS-1861; DB11794; NSC-777718; SB17265; NCGC00386313-07; AC-32951; AS-17041; DA-46989; HY-13902; QC-10953; FT-0700136; SW220202-1; A13289; D11148; M-6620; A857986; Q27089129; 5-(4-isopropylsulfonylphenyl)-3-[3-[4-(methylaminomethyl)phenyl]isoxazol-5-yl]pyrazin-2-amine; Synthesis of 3-[3-[4-[dideuterio(methylamino)methyl]phenyl]isoxazol-5-yl]-5-(4-isopropylsulfonylphenyl)pyrazin-2-amine
• Target: .; NOUNIPROTAC; [1]
• Formula: 7
• IsoSMILES: CC(C)S(=O)(=O)C1=CC=C(C=C1)C2=CN=C(C(=N2)C3=CC(=NO3)C4=CC=C(C=C4)CNC)N
• InChI: InChI=1S/C24H25N5O3S/c1-15(2)33(30,31)19-10-8-18(9-11-19)21-14-27-24(25)23(28-21)22-12-20(29-32-22)17-6-4-16(5-7-17)13-26-3/h4-12,14-15,26H,13H2,1-3H3,(H2,25,27)
• InChIKey: JZCWLJDSIRUGIN-UHFFFAOYSA-N
• PubChem CID: 59472121
• ChEBI ID: CHEBI:131166
• DrugBank ID: DB11794

Type(s) of Resistant Mechanism of This Drug

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

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

Solid tumour/cancer [ICD-11: 2A00-2F9Z]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Oxalosuccinate decarboxylase (IDH1) [2]

• Molecule Alteration: Missense mutation; p.R132H (c.395G>A)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: IDH2 cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: IDH1 cells; N.A.; Homo sapiens (Human); N.A.
• In Vivo Model: Female athymic nu/nu mouse PDX model; Mus musculus
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: The oncometabolite, 2-hydroxyglutarate, renders IDH1/2 mutant cancer cells deficient in homologous recombination and confers vulnerability to synthetic lethal targeting with PARP inhibitors.

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.
• Ref 2: 2-Hydroxyglutarate produced by neomorphic IDH mutations suppresses homologous recombination and induces PARP inhibitor sensitivitySci Transl Med. 2017 Feb 1;9(375):eaal2463. doi: 10.1126/scitranslmed.aal2463.