General
Preferred name
DUVELISIB
Synonyms
INK1197 ()
IPI-145 ()
INK-1197 ()
CS-0888 ()
COPIKTRA ()
DUVELISIB HYDRATE ()
DUVELISIB MONOHYDRATE ()
INK-1147 ()
Duvelisib (IPI-145) ()
P&D ID
PD010647
CAS
1201438-56-3
Tags
available
drug
Approved by
EMA
FDA
First approval
2018
Drug Status
investigational
approved
Drug indication
Follicular lymphoma
Coronavirus Disease 2019 (COVID-19)
Arthritis
Small lymphocytic lymphoma
Max Phase
Phase 4
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
INDICATION
Duvelisib is indicated for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) after at least two prior therapies.[L4586]; ; The CLL is a cancer of the blood stem cells which are the blood cells that can develop into different types of cells. In leukemia, there is an overproduction of cells that are abnormal and do not mature into blood cells and thus, they just crowd out normal cells and impair their normal function. In lymphocyte leukemia, the abnormal cell growth is observed in the lymphoid cells which are the type of blood cells that mature into lymphocytes. The CLL is the type of lymphocytic leukemia that develops slowly over months or years.[L4587] The SLL is a very similar disease to the CLL and these terms are usually referred interchangeably. The only difference between these two diseases is that in CLL the cells are found mostly in the blood and bone marrow while in SLL, the cells are mainly found in the lymph nodes.[L4588]; ; As well, duvelisib obtained an accelerated approval for the treatment of adult patients with relapsed or refractory follicular lymphoma after at least two prior systemic therapies. This approval is still under the status of continued approval and it is restrained to confirmatory trials.[L4586]; ; The follicular lymphoma is a B-cell lymphoma that clusters in the lymph nodes or other tissues.[L4589]
MOA
Duvelisib acts as a strong reversible inhibitor of the isoform gamma and delta of the phosphoinositide3-kinase (PI3K).[A39028] PI3K plays a very important role in innate and adaptative immunity and the inhibition of the form delta and gamma has been very important for the suppression of immunity.[A39031]; ; The activity of PI3K gamma and delta is restricted to hematopoietic cells and it is necessary for normal B cell development. In lymphomas, the activation of PI3K is enlarged to promote unlimited growth and survival. Hence, inhibition of PI3K can provide an inhibition of the signaling from BCR, inhibition of a cytokine signaling from the microenvironment and enhancement of anti-tumor immunity.[A39032] The specific mechanism of this PI3K inhibitors are further described as follows:; ; -BCR activates signaling pathways after antigen engagement and it is also critical for the physiologic life of the lymphocytes and neoplastic lymphomas. In CLL, BCR reacts to auto- and exo-antigens to promote clonal expansion. This sustained presence of BCR activates delta PI3K producing a pro-survival pathway of the neoplastic cells which already present a higher activity of PI3K. Thus, the blockade of PI3K will limit the activity of BCR and the driven physiology of the lymphoma.[A39032]; ; -The inhibition of PI3K can also inhibit paracrine and autocrine pro-survival signals mediated by adhesion molecules, chemokines and soluble factors. This activity is attained due to the fact that several downstream signals convey on PI3K.[A39034]; ; -It has been reported that inactivation of PI3K produces a significant resistance to tumorigenesis. This data suggests that inhibition of PI3K can facilitate recognition and elimination of tumor cells.[A39032]; ; In summary, duvelisib inhibits the isoform delta of PI3K which is necessary for cell proliferation and survival and the isoform gamma which is critical for cytokine signaling and the pro-inflammatory response.[A39034]
DESCRIPTION
Duvelisib is an orally active, dual inhibitor of phosphoinositide-3 kinase (PI3K)-δ and PI3K-γ . It was developed for the treatment of advanced hematolgical malignancies including CLL, SLL and FL .
(GtoPdb)
PHARMACODYNAMICS
Preclinical data showed that duvelisib presents cytotoxic actions at micromolar doses and antagonizes the activation of downstream signaling even in the presence of the mutation BTK C481S, which allows for the treatment of patients resistant to ibrutinib.[A39032]; ; In clinical trials, duvelisib was compared to ofatumumab in patients with chronic lymphocytic leukemia or small lymphocytic leukemia. This trials reported a median progression-free survival of 16.4 months and an overall response rate of 78% which were almost 2-fold what it was reported for ofatumumab.[L4585]; ; In clinical trials of follicular lymphoma, duvelisib presented and overall response rate of 42% from which almost all the patients observed a partial response. Of the responding patients, 43% maintained the response for at least 6 months and 17% for at least 12 months.[L4585]
DESCRIPTION
Duvelisib is a selective inhibitor of phosphoinositide-3 kinase (PI3K)-δ and PI3K-γ .
DESCRIPTION
On october 27, 2018, the FDA approved duvelisib to treat relapsed or refractory chronic lymphocytic leukemia, small lymphocytic lymphoma and follicular lymphoma
(PKIDB)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
4
Organisms
0
Compound Sets
21
AdooQ Bioactive Compound Library
Cayman Chemical Bioactives
ChEMBL Approved Drugs
ChEMBL Drugs
Drug Repurposing Hub
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP Approved Drugs
Guide to Pharmacology
Mcule NIBR MoA Box Subset
MedChem Express Bioactive Compound Library
NCATS Inxight Approved Drugs
NIH Approved Oncology Drugs
Novartis Chemogenetic Library (NIBR MoA Box)
PKIDB
ReFrame library
Selleckchem Bioactive Compound Library
TargetMol Bioactive Compound Library
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
31
Molecular Weight
416.12
Hydrogen Bond Acceptors
6
Hydrogen Bond Donors
2
Rotatable Bonds
4
Ring Count
5
Aromatic Ring Count
5
cLogP
4.48
TPSA
88.49
Fraction CSP3
0.09
Chiral centers
1.0
Largest ring
6.0
QED
0.45
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Pathway
PI3K/Akt/mTOR signaling
PI3K/Akt/mTOR
Target
PI3K??
PIK3CA, PIK3CB, PIK3CD, PIK3CG
PIK3CD
PIK3CG
PI3K
Member status
member
MOA
lipid kinase inhibitor
PI3K inhibitor
Therapeutic Class
Antiviral Agents
Source data
