Molecule Information

General Information of the Molecule (ID: Mol01967)

• Name: Zinc finger C3HC-type containing 1 (ZC3HC1) ,Homo sapiens
• Synonyms: ZC3HC1; NIPA; HSPC216
• Molecule Type: Protein
• Gene Name: ZC3HC1
• Gene ID: 51530
• Location: chr7:130,018,287-130,051,451[-]
• Sequence:
  MAAPCEGQAFAVGVEKNWGAVVRSPEGTPQKIRQLIDEGIAPEEGGVDAKDTSATSQSVN
  GSPQAEQPSLESTSKEAFFSRVETFSSLKWAGKPFELSPLVCAKYGWVTVECDMLKCSSC
  QAFLCASLQPAFDFDRYKQRCAELKKALCTAHEKFCFWPDSPSPDRFGMLPLDEPAILVS
  EFLDRFQSLCHLDLQLPSLRPEDLKTMCLTEDKISLLLHLLEDELDHRTDERKTTIKLGS
  DIQVHVTACILSVCGWACSSSLESMQLSLITCSQCMRKVGLWGFQQIESSMTDLDASFGL
  TSSPIPGLEGRPERLPLVPESPRRMMTRSQDATFSPGSEQAEKSPGPIVSRTRSWDSSSP
  VDRPEPEAASPTTRTRPVTRSMGTGDTPGLEVPSSPLRKAKRARLCSSSSSDTSSRSFFD
  PTSQHRDWCPWVNITLGKESRENGGTEPDASAPAEPGWKAVLTILLAHKQSSQPAETDSM
  SLSEKSRKVFRIFRQWESLCSC
• Function: Essential component of a SCF-type E3 ligase complex, SCF(NIPA), a complex that controls mitotic entry by mediating ubiquitination and subsequent degradation of cyclin B1 (CCNB1). Its cell-cycle-dependent phosphorylation regulates the assembly of the SCF(NIPA) complex, restricting CCNB1 ubiquitination activity to interphase. Its inactivation results in nuclear accumulation of CCNB1 in interphase and premature mitotic entry. May have an antiapoptotic role in NPM-ALK-mediated signaling events.
• Uniprot ID: ZC3C1_HUMAN
• Ensembl ID: ENSG00000091732
• HGNC ID: HGNC:29913

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  EADR: Epigenetic Alteration of DNA, RNA or Protein

Drug Resistance Data Categorized by Drug

Approved Drug(s) 2 drug(s) in total

Alectinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: NPM-ALK-Positive anaplastic large cell lymphoma [1]

• Resistant Disease: NPM-ALK-Positive anaplastic large cell lymphoma [ICD-11: 2A81.8]
• Resistant Drug: Alectinib
• Molecule Alteration: Expression; Up-regulation
• 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.

Disease Class: NPM-ALK-Positive anaplastic large cell lymphoma [1]

• Resistant Disease: NPM-ALK-Positive anaplastic large cell lymphoma [ICD-11: 2A81.8]
• Resistant Drug: Alectinib
• Molecule Alteration: Mutation; p.L1122V+p.F1174V+p.L1196M+p.L1198F+p.S1206C+p.L1122V+p.L1196M+p.F1174V+p.L1198F+p.L1196M+p.D1203N
• 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.

Ceritinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: NPM-ALK-Positive anaplastic large cell lymphoma [1]

• Resistant Disease: NPM-ALK-Positive anaplastic large cell lymphoma [ICD-11: 2A81.8]
• Resistant Drug: Ceritinib
• Molecule Alteration: Expression; Up-regulation
• 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.

Disease Class: NPM-ALK-Positive anaplastic large cell lymphoma [1]

• Resistant Disease: NPM-ALK-Positive anaplastic large cell lymphoma [ICD-11: 2A81.8]
• Resistant Drug: Ceritinib
• Molecule Alteration: Mutation; p.L1122V+p.139S+p.L1198F+p.S1206C+p.L1122V+p.L1196M+p.F1174V+p.L1198F+p.L1196M+p.D1203N
• 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.

Clinical Trial Drug(s) 1 drug(s) in total

AP26113

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: NPM-ALK-Positive anaplastic large cell lymphoma [1]

• Resistant Disease: NPM-ALK-Positive anaplastic large cell lymphoma [ICD-11: 2A81.8]
• Resistant Drug: AP26113
• Molecule Alteration: Expression; Up-regulation
• 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.

Disease Class: NPM-ALK-Positive anaplastic large cell lymphoma [1]

• Resistant Disease: NPM-ALK-Positive anaplastic large cell lymphoma [ICD-11: 2A81.8]
• Resistant Drug: AP26113
• 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
• 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.

Investigative Drug(s) 2 drug(s) in total

ASP3026

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: NPM-ALK-Positive anaplastic large cell lymphoma [1]

• Resistant Disease: NPM-ALK-Positive anaplastic large cell lymphoma [ICD-11: 2A81.8]
• Resistant Drug: ASP3026
• Molecule Alteration: Expression; Up-regulation
• 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.

Disease Class: NPM-ALK-Positive anaplastic large cell lymphoma [1]

• Resistant Disease: NPM-ALK-Positive anaplastic large cell lymphoma [ICD-11: 2A81.8]
• Resistant Drug: ASP3026
• 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
• 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.

Clozatinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: NPM-ALK-Positive anaplastic large cell lymphoma [1]

• Resistant Disease: NPM-ALK-Positive anaplastic large cell lymphoma [ICD-11: 2A81.8]
• Resistant Drug: Clozatinib
• Molecule Alteration: Expression; Up-regulation
• 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.

Disease Class: NPM-ALK-Positive anaplastic large cell lymphoma [1]

• Resistant Disease: NPM-ALK-Positive anaplastic large cell lymphoma [ICD-11: 2A81.8]
• Resistant Drug: Clozatinib
• Molecule Alteration: Mutation; p.L1122V+p.139S+p.L1196M+p.S1206C+p.L1122V+p.L1196M+p.L1196M+p.D1203N
• 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