Drug Information

Drug (ID: DG00632) and It's Reported Resistant Information

• Name: ASP3026
• Synonyms: ASP3026; 1097917-15-1; ASP-3026; ASP 3026; N2-[2-Methoxy-4-[4-(4-methyl-1-piperazinyl)-1-piperidinyl]phenyl]-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-1,3,5-triazine-2,4-diamine; UNII-HP4L6MXF10; HP4L6MXF10; 2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)-1,3,5-triazine-2,4-diamine; 4-N-[2-Methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-2-N-(2-propan-2-ylsulfonylphenyl)-1,3,5-triazine-2,4-diamine; N4-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-N2-(2-propan-2-ylsulfonylphenyl)-1,3,5-triazine-2,4-diamine; F6O; MLS006011176; GTPL7740; SCHEMBL2827739; CHEMBL3545360; C29H40N8O3S; AOB6601; DTXSID90149038; EX-A140; QCR-144; CHEBI:167650; HMS3673C17; BCP06436; XTB91715; 2229AH; MFCD21609265; NSC765865; NSC799336; s8054; ZINC68120928; AKOS025142083; CCG-270132; CS-0787; DB12729; NSC-765865; NSC-799336; SB19387; NCGC00345791-01; NCGC00345791-09; AC-28466; AS-16959; DA-35322; HY-13326; N2-(2-(isopropylsulfonyl)phenyl)-N4-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)-1,3,5-triazine-2,4-diamine; SMR004702945; FT-0755075; J-523409; Q27074543; N(2)-[2-methoxy-4-[4-(4-methyl-1-piperazinyl)-1-piperidinyl]phenyl]-N(4)-[2-[(1-methylethyl)sulfonyl]phenyl]-1,3,5-triazine-2,4-diamine; N-{2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}-N'-[2-(propan-2-ylsulfonyl)phenyl]-1,3,5-triazine-2,4-diamine; N-{2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}-N'-[2-(propane-2-sulfonyl)phenyl]-1,3,5-triazine-2,4-diamine
• Indication:
  In total 1 Indication(s)
  Diffuse large B-cell lymphoma [ICD-11: 2A81]; Investigative; [1]
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
  Diffuse large B-cell lymphoma [ICD-11: 2A81]; [1]
• Target: ALK tyrosine kinase receptor (ALK); ALK_HUMAN; [1]
• Formula: C29H40N8O3S
• IsoSMILES: CC(C)S(=O)(=O)C1=CC=CC=C1NC2=NC(=NC=N2)NC3=C(C=C(C=C3)N4CCC(CC4)N5CCN(CC5)C)OC
• InChI: 1S/C29H40N8O3S/c1-21(2)41(38,39)27-8-6-5-7-25(27)33-29-31-20-30-28(34-29)32-24-10-9-23(19-26(24)40-4)36-13-11-22(12-14-36)37-17-15-35(3)16-18-37/h5-10,19-22H,11-18H2,1-4H3,(H2,30,31,32,33,34)
• InChIKey: MGGBYMDAPCCKCT-UHFFFAOYSA-N
• PubChem CID: 25134326
• TTD Drug ID: D09GEK

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

Diffuse large B-cell lymphoma [ICD-11: 2A81]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Zinc finger C3HC-type containing 1 (ZC3HC1) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: NPM-ALK-Positive anaplastic large cell lymphoma [ICD-11: 2A81.8]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SUP-M2 cells; Colon; Homo sapiens (Human); CVCL_2209
• In Vitro Model: KARPAS-299 cells; Peripheral blood; Homo sapiens (Human); CVCL_1324
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Proliferation assay
• Mechanism Description: For KARPAS-299-derived cell lines, we observed oncogene overexpression as the main resistance mechanism, whereas in SUP-M2-derived cell lines, we identified several point mutations located within the NPM-ALK kinase domain, which could explain drug resistance.

Key Molecule: Zinc finger C3HC-type containing 1 (ZC3HC1) [1]

• Molecule Alteration: Mutation; p.L1122V+p.139S+p.F1174V+p.L1196M+p.L1198F+p.S1206C+p.L1122V+p.L1196M+p.F1174V+p.L1198F+p.L1196M+p.D1203N
• Resistant Disease: NPM-ALK-Positive anaplastic large cell lymphoma [ICD-11: 2A81.8]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SUP-M2 cells; Colon; Homo sapiens (Human); CVCL_2209
• In Vitro Model: KARPAS-299 cells; Peripheral blood; Homo sapiens (Human); CVCL_1324
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Proliferation assay
• Mechanism Description: For KARPAS-299-derived cell lines, we observed oncogene overexpression as the main resistance mechanism, whereas in SUP-M2-derived cell lines, we identified several point mutations located within the NPM-ALK kinase domain, which could explain drug resistance.

References

• Ref 1: Treatment Efficacy and Resistance Mechanisms Using the Second-Generation ALK Inhibitor AP26113 in Human NPM-ALK-Positive Anaplastic Large Cell Lymphoma .Mol Cancer Res. 2015 Apr;13(4):775-83. doi: 10.1158/1541-7786.MCR-14-0157. Epub 2014 Nov 24. 10.1158/1541-7786.MCR-14-0157