Drug Information

Drug (ID: DG01271) and It's Reported Resistant Information
Name
IPI-145
Synonyms
Duvelisib; 1201438-56-3; IPI-145; INK-1197; (S)-3-(1-((9H-Purin-6-yl)amino)ethyl)-8-chloro-2-phenylisoquinolin-1(2H)-one; UNII-610V23S0JI; IPI 145; Copiktra; IPI-145 (INK1197); (S)-3-(1-(9H-purin-6-ylamino)ethyl)-8-chloro-2-phenylisoquinolin-1(2H)-one; 610V23S0JI; INK-1147; 8-chloro-2-phenyl-3-[(1S)-1-(7H-purin-6-ylamino)ethyl]isoquinolin-1-one; Duvelisib (IPI-145, INK1197); Copiktra (TN); Duvelisib monohydrate; IPI145; Duvelisib [USAN:INN]; Duvelisib hydrate; 1(2H)-Isoquinolinone, 8-chloro-2-phenyl-3-((1S)-1-(9H-purin-6-ylamino)ethyl)-; 1(2H)-Isoquinolinone, 8-chloro-2-phenyl-3-[(1S)-1-(9H-purin-6-ylamino)ethyl]-; INK1197; Duvelisib (USAN/INN); Duvelisib (IPI-145); SCHEMBL153543; GTPL7795; CHEMBL3039502; SCHEMBL18343557; SCHEMBL19670020; SCHEMBL20580104; DTXSID80152697; SYN1175; CHEBI:131169; AMY24208; AOB87713; BCP07042; EX-A1562; BDBM50193013; MFCD15144635; NSC772469; s7028; ZINC88346058; AKOS022186370; AKOS037515795; IPI-145, INK 1197, Duvelisib; CCG-268854; CS-0888; DB11952; NSC-772469; 8-chloro-2-phenyl-3-((1S)-1-(9H-purin-6-ylamino)ethyl)-1(2H)-isoquinolinone; NCGC00351482-01; AC-30239; AS-16309; compound 4904 [Patent US8193182]; HY-17044; QC-10232; SW219822-1; X5816; D10555; Q27077129; IPI-145 pound>>INK1197; IPI 145; IPI145; INK-1197; INK 1197; (S)-3-(1-(7H-purin-6-ylamino)ethyl)-8-chloro-2-phenylisoquinolin-1(2H)-one; 8-Chloro-2-phenyl-3-((1S)-1-(7H-purin-6-ylamino)ethyl)isoquinolin-1(2H)-one; INK-1197; ; ; IPI-145; ; ; 8-Chloro-2-phenyl-3-[(1S)-1-(7H-purin-6-ylamino)ethyl]isoquinolin-1-one
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Indication
In total 3 Indication(s)
Arthritis [ICD-11: FA20]
Approved
[1]
Follicular lymphoma [ICD-11: 2A80]
Approved
[1]
Small lymphocytic lymphoma [ICD-11: 2A82]
Approved
[1]
Structure
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 delta (PIK3CD) PK3CD_HUMAN [1]
PI3-kinase gamma (PIK3CG) PK3CG_HUMAN [1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
C22H17ClN6O
IsoSMILES
C[C@@H](C1=CC2=C(C(=CC=C2)Cl)C(=O)N1C3=CC=CC=C3)NC4=NC=NC5=C4NC=N5
InChI
1S/C22H17ClN6O/c1-13(28-21-19-20(25-11-24-19)26-12-27-21)17-10-14-6-5-9-16(23)18(14)22(30)29(17)15-7-3-2-4-8-15/h2-13H,1H3,(H2,24,25,26,27,28)/t13-/m0/s1
InChIKey
SJVQHLPISAIATJ-ZDUSSCGKSA-N
PubChem CID
50905713
ChEBI ID
CHEBI:131169
TTD Drug ID
D0RU0O
VARIDT ID
DR00276
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
Click to Show/Hide the Resistance Disease of This Class
Mature B-cell neoplasms/lymphoma [ICD-11: 2A85]
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Interleukin 6 receptor (IL6R) [1]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Non-Hodgkin lymphoma [ICD-11: 2A85.5]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model RWPE-1 cells Prostate Homo sapiens (Human) CVCL_3791
SW1116 cells Colon Homo sapiens (Human) CVCL_0544
HCT15 cells Colon Homo sapiens (Human) CVCL_0292
LS174T cells Colon Homo sapiens (Human) CVCL_1384
NCI-H716 cells Colon Homo sapiens (Human) CVCL_1581
SW948 cells Colon Homo sapiens (Human) CVCL_0632
C4-2B cells Prostate Homo sapiens (Human) CVCL_4784
OCI-Ly1 cells Bone marrow Homo sapiens (Human) CVCL_1879
Riva cells Pleural effusion Homo sapiens (Human) N.A.
SU-DHL2 cells Pleural effusion Homo sapiens (Human) CVCL_9550
U2932 (ABC-DLBCL) cells Ascites Homo sapiens (Human) CVCL_1896
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

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