Drug Information

Drug (ID: DG01270) and It's Reported Resistant Information

• Name: Copanlisib
• Synonyms: Copanlisib; 1032568-63-0; BAY 80-6946; Aliqopa; BAY-80-6946; BAY80-6946; UNII-WI6V529FZ9; BAY 80-6946 (Copanlisib); 2-amino-N-[7-methoxy-8-(3-morpholin-4-ylpropoxy)-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl]pyrimidine-5-carboxamide; WI6V529FZ9; Copanlisib (BAY 80-6946); 2-Amino-N-[2,3-dihydro-7-methoxy-8-[3-(4-morpholinyl)propoxy]imidazo[1,2-c]quinazolin-5-yl]-5-pyrimidinecarboxamide; 2-amino-N-(7-methoxy-8-(3-morpholinopropoxy)-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)pyrimidine-5-carboxamide; 2-amino-N-[7-methoxy-8-(3-morpholin-4-ylpropoxy)-2,3-dihydro-1H-imidazo[1,2-c]quinazolin-5-ylidene]pyrimidine-5-carboxamide; copanlisibum; Copanlisib tris-HCl; Copanlisib (USAN/INN); Copanlisib [USAN:INN]; GTPL7875; SCHEMBL1655478; BAY 80-6946; Copanlisib; BAY-80-6946 tris-HCl; Copanlisib; BAY-80-6946; CHEMBL3218576; SCHEMBL13084037; DTXSID00145728; CHEBI:173077; C23H28N8O4; BCP04754; EX-A2005; 2253AH; BDBM50204093; MFCD18633201; NSC760443; NSC800076; NSC809693; NSC816437; s2802; ZINC68247389; AKOS025290222; BAY-806946; CS-0741; DB12483; NSC-760443; NSC-800076; NSC-809693; NSC-816437; PB22956; VS-0128; NCGC00346457-01; NCGC00346457-02; NCGC00346457-04; 2-amino-N-(7-methoxy-8-(3-morpholinopropoxy)-2,3-dihydroimidazo(1,2-c)quinazolin-4-yl)pyrimidine-5-carboxamide; AC-28438; BC164810; HY-15346; QC-10511; D10867; Q19903876; 2-amino-N-[7-methoxy-8-(3-morpholin-4-ylpropoxy)-2,3-dihydroimidazo[1.2-c]quinazolin-5-yl]pyrimidine-5-carboxamide; 2-amino-N-{7-methoxy-8-[3-(morpholin-4-yl)propoxy]-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl}pyrimidine-5-carboxamide; BAY-80-6946; ; ; 2-Amino-N-[7-methoxy-8-(3-morpholin-4-ylpropoxy)-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl]pyrimidine-5-carboxamide
• Indication:
  In total 3 Indication(s)
  Follicular lymphoma [ICD-11: 2A80]; Approved; [1]
  Non-hodgkin lymphoma [ICD-11: 2B33]; Approved; [1]
  Non-hodgkin lymphoma [ICD-11: 2B33]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
  Mature B-cell neoplasms/lymphoma [ICD-11: 2A85]; [1]
• Target: PI3-kinase alpha (PIK3CA); PK3CA_HUMAN; [1]
• Target: PI3-kinase delta (PIK3CD); PK3CD_HUMAN; [1]
• Target: PI3-kinase gamma (PIK3CG); PK3CG_HUMAN; [1]
• Formula: C23H28N8O4
• IsoSMILES: COC1=C(C=CC2=C3NCCN3C(=NC(=O)C4=CN=C(N=C4)N)N=C21)OCCCN5CCOCC5
• InChI: 1S/C23H28N8O4/c1-33-19-17(35-10-2-6-30-8-11-34-12-9-30)4-3-16-18(19)28-23(31-7-5-25-20(16)31)29-21(32)15-13-26-22(24)27-14-15/h3-4,13-14,25H,2,5-12H2,1H3,(H2,24,26,27)
• InChIKey: MWYDSXOGIBMAET-UHFFFAOYSA-N
• PubChem CID: 135565596
• TTD Drug ID: D0S5LD
• INTEDE ID: DR0378
• DrugBank ID: DB12483

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

Mature B-cell neoplasms/lymphoma [ICD-11: 2A85]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Interleukin 6 receptor (IL6R) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Non-Hodgkin lymphoma [ICD-11: 2A85.5]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: RWPE-1 cells; Prostate; Homo sapiens (Human); CVCL_3791
• In Vitro Model: SW1116 cells; Colon; Homo sapiens (Human); CVCL_0544
• In Vitro Model: HCT15 cells; Colon; Homo sapiens (Human); CVCL_0292
• In Vitro Model: LS174T cells; Colon; Homo sapiens (Human); CVCL_1384
• In Vitro Model: NCI-H716 cells; Colon; Homo sapiens (Human); CVCL_1581
• In Vitro Model: SW948 cells; Colon; Homo sapiens (Human); CVCL_0632
• In Vitro Model: C4-2B cells; Prostate; Homo sapiens (Human); CVCL_4784
• In Vitro Model: OCI-Ly1 cells; Bone marrow; Homo sapiens (Human); CVCL_1879
• In Vitro Model: Riva cells; Pleural effusion; Homo sapiens (Human); N.A.
• In Vitro Model: SU-DHL2 cells; Pleural effusion; Homo sapiens (Human); CVCL_9550
• In Vitro Model: U2932 (ABC-DLBCL) cells; Ascites; Homo sapiens (Human); CVCL_1896
• In Vitro Model: BJAB cells; Groin; Homo sapiens (Human); CVCL_5711
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: Cytokine arrays revealed upregulation of interleukin (IL)-6 in both copanlisib- and duvelisib-resistant cell lines. Phosphorylated STAT5, AKT, p70S6K and MAPK were increased in copanlisib-resistant B-cell lymphoma cells, whereas phosphorylated STAT3 and NF-kappaB were increased in duvelisib-resistant T cell lymphoma cells. Conversely, depletion of IL-6 sensitized both resistant cell lines, and led to downregulation of phosphorylated STAT3 and STAT5 in copanlisib- and duvelisib-resistant cells, respectively. Moreover, combined treatment with a JAK inhibitor (BSK805) and a PI3K inhibitor circumvented the acquired resistance to PI3K inhibitors in lymphoma, and concurrent inhibition of the activated pathways produced combined effects.IL-6-induced STAT3 or STAT5 activation is a critical mechanism underlying PI3K inhibitor resistance in lymphoma, supporting the utility of IL-6 as an effective biomarker to predict therapeutic response to PI3K inhibitors.

References

• Ref 1: Interleukin-6 mediates resistance to PI3K-pathway-targeted therapy in lymphoma .BMC Cancer. 2019 Oct 10;19(1):936. doi: 10.1186/s12885-019-6057-7. 10.1186/s12885-019-6057-7