Drug Information

Drug (ID: DG00630) and It's Reported Resistant Information

• Name: AP26113
• Synonyms: AP26113; 1197958-12-5; ALK-IN-1; Brigatinib-analog; (2-((5-chloro-2-((4-(4-(dimethylamino)piperidin-1-yl)-2-methoxyphenyl)amino)pyrimidin-4-yl)amino)phenyl)dimethylphosphine oxide; UNII-3DGD69C6PV; AP26113-analog; 5-chloro-2-N-[4-[4-(dimethylamino)piperidin-1-yl]-2-methoxyphenyl]-4-N-(2-dimethylphosphorylphenyl)pyrimidine-2,4-diamine; 3DGD69C6PV; CHEMBL3397300; 1197958-12-5 (analog); 5-Chloro-N~2~-{4-[4-(dimethylamino)piperidin-1-yl]-2-methoxyphenyl}-N~4~-[2-(dimethylphosphoryl)phenyl]pyrimidine-2,4-diamine; 2,4-Pyrimidinediamine, 5-chloro-N2-(4-(4-(dimethylamino)-1-piperidinyl)-2-methoxyphenyl)-N4-(2-(dimethylphosphinyl)phenyl)-; 2,4-Pyrimidinediamine, 5-chloro-N2-[4-[4-(dimethylamino)-1-piperidinyl]-2-methoxyphenyl]-N4-[2-(dimethylphosphinyl)phenyl]-; Brigatinib analog; 5-Chloro-N2-(4-(4-(dimethylamino)piperidin-1-yl)-2-methoxyphenyl)-N4-(2-(dimethylphosphoryl)phenyl)pyrimidine-2,4-diamine; 5-CHLORO-N2-{4-[4-(DIMETHYLAMINO)PIPERIDIN-1-YL]-2-METHOXYPHENYL}-N4-[2-(DIMETHYLPHOSPHORYL)PHENYL]PYRIMIDINE-2,4-DIAMINE; Brigatinib(AP26113); C26H34ClN6O2P; SCHEMBL11916416; DTXSID30725416; EX-A770; AP26113;ALK-IN-1; HMS3652H14; HMS3673I09; BCP06648; 2218AH; BDBM50062357; MFCD23704187; NSC776763; NSC800977; s7000; ZINC89630357; AKOS025401944; AKOS032949980; AP 26113-analog, Brigatinib-analog; CCG-264698; CS-1368; NSC-776763; NSC-800977; SB16487; NCGC00351602-02; NCGC00351602-05; NCGC00351602-09; 5-Chloro-N2-(4-(4-(dimethylamino)-1-piperidinyl)-2-methoxyphenyl)-N4-(2-(dimethylphosphinyl)phenyl)-2,4-pyrimidinediamine; AC-27470; AS-75104; DA-35325; HY-13464; QC-11659; FT-0696829; SW219566-1; Q4653190; E5J
• Indication:
  In total 1 Indication(s)
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; Phase 2; [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: C26H34ClN6O2P
• IsoSMILES: CN(C)C1CCN(CC1)C2=CC(=C(C=C2)NC3=NC=C(C(=N3)NC4=CC=CC=C4P(=O)(C)C)Cl)OC
• InChI: 1S/C26H34ClN6O2P/c1-32(2)18-12-14-33(15-13-18)19-10-11-21(23(16-19)35-3)30-26-28-17-20(27)25(31-26)29-22-8-6-7-9-24(22)36(4,5)34/h6-11,16-18H,12-15H2,1-5H3,(H2,28,29,30,31)
• InChIKey: OVDSPTSBIQCAIN-UHFFFAOYSA-N
• PubChem CID: 57390074
• TTD Drug ID: D0O9PQ

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