Details of the Drug

General Information of Drug (ID: DMWA24P)

Drug Name

IPI-145

Synonyms

Duvelisib; 1201438-56-3; INK-1197; UNII-610V23S0JI;

Indication

Disease Entry	ICD 11	Status	REF
Follicular lymphoma	2A80	Approved	[1]
Small lymphocytic lymphoma	2A82.0	Approved	[1]
Arthritis	FA20	Phase 3	[2], [3]

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

416.9

Topological Polar Surface Area (xlogp)

4.1

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 1.6-5.7 mcg/L [4]
Absorption Tmax: The time to maximum plasma concentration (Tmax) is 30-150 min [4]
Bioavailability: The bioavailability of drug is less than 10% [4]
Clearance: The clearance of drug is 3.6-11.2 L/h [5]
Elimination: From the administered dose, 79% os excreted in feces and 14% in urine [6]
Half-life: The concentration or amount of drug in body reduced by one-half in 5.2 - 10.9 hours [5]
Metabolism: The drug is metabolized via the CYP3A4 [7]
Vd: The volume of distribution (Vd) of drug is 26-102 L [5]

Chemical Identifiers

Formula: C22H17ClN6O
IUPAC Name: 8-chloro-2-phenyl-3-[(1S)-1-(7H-purin-6-ylamino)ethyl]isoquinolin-1-one
Canonical SMILES: C[C@@H](C1=CC2=C(C(=CC=C2)Cl)C(=O)N1C3=CC=CC=C3)NC4=NC=NC5=C4NC=N5
InChI: 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

Cross-matching ID

PubChem CID: 50905713
ChEBI ID: CHEBI:131169
CAS Number: 1201438-56-3
DrugBank ID: DB11952
TTD ID: D0RU0O
VARIDT ID: DR00276
ACDINA ID: D01025

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
PI3-kinase delta (PIK3CD)	TTGBPJE	PK3CD_HUMAN	Modulator	[3]
PI3-kinase gamma (PIK3CG)	TTHBTOP	PK3CG_HUMAN	Modulator	[3]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease

Follicular lymphoma

ICD Disease Classification

2A80

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
PI3-kinase gamma (PIK3CG)	DTT	PIK3CG	1.98E-01	-0.05	-0.55

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from IPI-145 (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Remdesivir	DMBFZ6L	Moderate	Increased risk of hepatotoxicity by the combination of IPI-145 and Remdesivir.	1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019]	[23]
Ivosidenib	DM8S6T7	Moderate	Increased metabolism of IPI-145 caused by Ivosidenib mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[24]
Gilteritinib	DMWQ4MZ	Moderate	Decreased clearance of IPI-145 due to the transporter inhibition by Gilteritinib.	Acute myeloid leukaemia [2A60]	[25]
Oliceridine	DM6MDCF	Major	Decreased metabolism of IPI-145 caused by Oliceridine mediated inhibition of CYP450 enzyme.	Acute pain [MG31]	[26]
Troleandomycin	DMUZNIG	Major	Decreased metabolism of IPI-145 caused by Troleandomycin mediated inhibition of CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[24]
Pexidartinib	DMS2J0Z	Major	Decreased metabolism of IPI-145 caused by Pexidartinib mediated inhibition of CYP450 enzyme.	Bone/articular cartilage neoplasm [2F7B]	[27]
LY2835219	DM93VBZ	Moderate	Decreased metabolism of IPI-145 caused by LY2835219 mediated inhibition of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[28]
PF-04449913	DMSB068	Moderate	Decreased metabolism of IPI-145 caused by PF-04449913 mediated inhibition of CYP450 enzyme.	Chronic myelomonocytic leukaemia [2A40]	[29]
Polatuzumab vedotin	DMF6Y0L	Moderate	Decreased metabolism of IPI-145 caused by Polatuzumab vedotin mediated inhibition of CYP450 enzyme.	Diffuse large B-cell lymphoma [2A81]	[30]
Eslicarbazepine	DMZREFQ	Moderate	Increased metabolism of IPI-145 caused by Eslicarbazepine mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[24]
Tazemetostat	DMWP1BH	Major	Decreased metabolism of IPI-145 caused by Tazemetostat mediated inhibition of CYP450 enzyme.	Follicular lymphoma [2A80]	[31]
Ripretinib	DM958QB	Moderate	Decreased metabolism of IPI-145 caused by Ripretinib mediated inhibition of CYP450 enzyme.	Gastrointestinal stromal tumour [2B5B]	[23]
Avapritinib	DMK2GZX	Major	Decreased metabolism of IPI-145 caused by Avapritinib mediated inhibition of CYP450 enzyme.	Gastrointestinal stromal tumour [2B5B]	[25]
MK-1439	DM215WE	Minor	Decreased metabolism of IPI-145 caused by MK-1439 mediated inhibition of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[32]
Pemigatinib	DM819JF	Major	Decreased metabolism of IPI-145 caused by Pemigatinib mediated inhibition of CYP450 enzyme.	Liver cancer [2C12]	[33]
Brigatinib	DM7W94S	Moderate	Increased metabolism of IPI-145 caused by Brigatinib mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[23]
PF-06463922	DMKM7EW	Moderate	Increased metabolism of IPI-145 caused by PF-06463922 mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[24]
Selpercatinib	DMZR15V	Major	Decreased metabolism of IPI-145 caused by Selpercatinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[26]
Ubrogepant	DM749I3	Moderate	Decreased metabolism of IPI-145 caused by Ubrogepant mediated inhibition of CYP450 enzyme.	Migraine [8A80]	[34]
Rimegepant	DMHOAUG	Moderate	Decreased metabolism of IPI-145 caused by Rimegepant mediated inhibition of CYP450 enzyme.	Migraine [8A80]	[35]
Siponimod	DM2R86O	Major	Decreased metabolism of IPI-145 caused by Siponimod mediated inhibition of CYP450 enzyme.	Multiple sclerosis [8A40]	[23]
Ocrelizumab	DMEZ2KH	Moderate	Additive immunosuppressive effects by the combination of IPI-145 and Ocrelizumab.	Multiple sclerosis [8A40]	[36]
Ozanimod	DMT6AM2	Major	Additive immunosuppressive effects by the combination of IPI-145 and Ozanimod.	Multiple sclerosis [8A40]	[25]
Fedratinib	DM4ZBK6	Moderate	Decreased metabolism of IPI-145 caused by Fedratinib mediated inhibition of CYP450 enzyme.	Myeloproliferative neoplasm [2A20]	[24]
Entrectinib	DMMPTLH	Major	Decreased metabolism of IPI-145 caused by Entrectinib mediated inhibition of CYP450 enzyme.	Non-small cell lung cancer [2C25]	[25]
Darolutamide	DMV7YFT	Minor	Decreased metabolism of IPI-145 caused by Darolutamide mediated inhibition of CYP450 enzyme.	Prostate cancer [2C82]	[37]
Voxelotor	DMCS6M5	Moderate	Decreased metabolism of IPI-145 caused by Voxelotor mediated inhibition of CYP450 enzyme.	Sickle-cell disorder [3A51]	[38]
Telotristat ethyl	DMDIYFZ	Moderate	Increased metabolism of IPI-145 caused by Telotristat ethyl mediated induction of CYP450 enzyme.	Small intestine developmental anomaly [DA90]	[24]
Larotrectinib	DM26CQR	Moderate	Decreased clearance of IPI-145 due to the transporter inhibition by Larotrectinib.	Solid tumour/cancer [2A00-2F9Z]	[23]
Elagolix	DMB2C0E	Moderate	Increased metabolism of IPI-145 caused by Elagolix mediated induction of CYP450 enzyme.	Uterine fibroid [2E86]	[24]
Fluticasone	DMGCSVF	Moderate	Decreased metabolism of IPI-145 caused by Fluticasone mediated inhibition of CYP450 enzyme.	Vasomotor/allergic rhinitis [CA08]	[23]
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⏷ Show the Full List of 31 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Crospovidone	E00626	Not Available	Disintegrant
Gelatin	E00630	Not Available	Other agent
Magnesium stearate	E00208	11177	lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Haematite red	E00236	14833	Colorant
Hydrophobic colloidal silica	E00285	24261	Anticaking agent; Emulsion stabilizing agent; Glidant; Suspending agent; Viscosity-controlling agent
Cellulose microcrystalline	E00698	Not Available	Adsorbent; Suspending agent; Diluent
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⏷ Show the Full List of 7 Pharmaceutical Excipients of This Drug

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Duvelisib 15 mg capsule	15 mg	Capsule	Oral
Duvelisib 25 mg capsule	25 mg	Capsule	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1	2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
2	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7795).
3	PI3K-delta and PI3K-gamma inhibition by IPI-145 abrogates immune responses and suppresses activity in autoimmune and inflammatory disease models. Chem Biol. 2013 Nov 21;20(11):1364-74.
4	Lacidipine Summary of Product Characteristics
5	Duvelisib, a novel oral dual inhibitor of PI3K-delta,gamma, is clinically active in advanced hematologic malignancies. Blood. 2018 Feb 22;131(8):877-887. doi: 10.1182/blood-2017-05-786566. Epub 2017 Nov 30.
6	Vangapandu HV, Jain N, Gandhi V: Duvelisib: a phosphoinositide-3 kinase delta/gamma inhibitor for chronic lymphocytic leukemia. Expert Opin Investig Drugs. 2017 May;26(5):625-632. doi: 10.1080/13543784.2017.1312338. Epub 2017 Apr 13.
7	FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
8	2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
9	2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
10	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2021
11	Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov. 2009 Aug;8(8):627-44.
12	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
13	Effective "activated PI3K syndrome"-targeted therapy with the PI3K inhibitor leniolisib. Blood. 2017 Nov 23;130(21):2307-2316.
14	Parsaclisib, a potent and highly selective PI3K inhibitor, in patients with relapsed or refractory B-cell malignancies. Blood. 2019 Apr 18;133(16):1742-1752.
15	The selective class I PI3K inhibitor CH5132799 targets human cancers harboring oncogenic PIK3CA mutations. Clin Cancer Res. 2011 May 15;17(10):3272-81.
16	INCB40093 is a selective PI3Kdelta inhibitor with potent antiproliferative activity against human B-cell tumors.
17	BAY 80-6946 is a highly selective intravenous PI3K inhibitor with potent p110 and p110 activities in tumor cell lines and xenograft models.Mol Cancer Ther.2013 Nov;12(11):2319-30.
18	Phase I study of oral rigosertib (ON 01910.Na), a dual inhibitor of the PI3K and Plk1 pathways, in adult patients with advanced solid malignancies. Clin Cancer Res. 2014 Mar 15;20(6):1656-65.
19	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2155).
20	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2156).
21	An integrin-targeted, pan-isoform, phosphoinositide-3 kinase inhibitor, SF1126, has activity against multiple myeloma in vivo.Cancer Chemother Pharmacol.2013 Apr;71(4):867-81.
22	First-in-Human Study of PF-05212384 (PKI-587), a Small-Molecule, Intravenous, Dual Inhibitor of PI3K and mTOR in Patients with Advanced Cancer. Clin Cancer Res. 2015 Apr 15;21(8):1888-95.
23	Cerner Multum, Inc. "Australian Product Information.".
24	Product Information. Copiktra (duvelisib). Verastem, Inc., Needham, MA.
25	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
26	Gunston GD, Mehta U "Potentially serious drug interactions with grapefruit juice." S Afr Med J 90 (2000): 41. [PMID: 10721388]
27	Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
28	Product Information. Verzenio (abemaciclib). Lilly, Eli and Company, Indianapolis, IN.
29	Product Information. Daurismo (glasdegib). Pfizer U.S. Pharmaceuticals Group, New York, NY.
30	Product Information. Polivy (polatuzumab vedotin). Genentech, South San Francisco, CA.
31	Product Information. Tazverik (tazemetostat). Epizyme, Inc, Cambridge, MA.
32	Product Information. Pifeltro (doravirine). Merck & Company Inc, Whitehouse Station, NJ.
33	Product Information. Pemazyre (pemigatinib). Incyte Corporation, Wilmington, DE.
34	Product Information. Ubrelvy (ubrogepant). Allergan Inc, Irvine, CA.
35	Product Information. Nurtec ODT (rimegepant). Biohaven Pharmaceuticals, New Haven, CT.
36	Product Information. Ocrevus (ocrelizumab). Genentech, South San Francisco, CA.
37	Product Information. Nubeqa (darolutamide). Bayer HealthCare Pharmaceuticals Inc., Whippany, NJ.
38	Canadian Pharmacists Association.