Details of the Drug

General Information of Drug (ID: DMYBIFS)

• Drug Name: Parsaclisib
• Synonyms: INCB050465; Parsaclisib free base; UNII-OS7097575K; 1426698-88-5 (free base); OS7097575K; 1426698-88-5; (4R)-4-{3-[(1S)-1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-5-chloro-2-ethoxy-6-fluorophenyl}pyrrolidin-2-one; INCB-050465; (4R)-4-(3-((1S)-1-(4-Amino-3-methyl-1H-pyrazolo(3,4-d)pyrimidin-1-yl)ethyl)-5-chloro-2-ethoxy-6-fluorophenyl)pyrrolidin-2-one; Parsaclisib [INN]; Parsaclisib [USAN]; Parsaclisib (USAN/INN); Parsaclisib [USAN:INN]; INCB050465 free base; INCB-050465 free base; CHEMBL4297615; SCHEMBL14736228; BDBM272573; EX-A2638; WHO 10589; DB14867; US10065963, 32c; HY-109068; CS-0033435; D11437; (R)-4-(3-((S)-1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-5-chloro-2-ethoxy-6-fluorophenyl)pyrrolidin-2-one; 2-Pyrrolidinone, 4-(3-((1S)-1-(4-amino-3-methyl-1H-pyrazolo(3,4-d)pyrimidin-1-yl)ethyl)-5-chloro-2-ethoxy-6-fluorophenyl)-, (4R)-

Indication

Disease Entry	ICD 11	Status	REF
Follicular lymphoma	2A80	Phase 2	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 432.9
  Topological Polar Surface Area (xlogp); 2.4
  Rotatable Bond Count (rotbonds); 5
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 7
• Chemical Identifiers:
  Formula: C20H22ClFN6O2
  IUPAC Name: (4R)-4-[3-[(1S)-1-(4-amino-3-methylpyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-5-chloro-2-ethoxy-6-fluorophenyl]pyrrolidin-2-one
  Canonical SMILES: CCOC1=C(C(=C(C=C1[C@H](C)N2C3=NC=NC(=C3C(=N2)C)N)Cl)F)[C@H]4CC(=O)NC4
  InChI: InChI=1S/C20H22ClFN6O2/c1-4-30-18-12(6-13(21)17(22)16(18)11-5-14(29)24-7-11)10(3)28-20-15(9(2)27-28)19(23)25-8-26-20/h6,8,10-11H,4-5,7H2,1-3H3,(H,24,29)(H2,23,25,26)/t10-,11-/m0/s1
  InChIKey: ZQPDJCIXJHUERQ-QWRGUYRKSA-N
• Cross-matching ID:
  PubChem CID: 86677874
  CAS Number: 1426698-88-5
  DrugBank ID: DB14867
  TTD ID: DP1SE6

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	Inhibitor	[2]

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 delta (PIK3CD)	DTT	PIK3CD	4.31E-16	-0.37	-0.91

References

• [1] ClinicalTrials.gov (NCT04434937) Open-Label Study of Parsaclisib, in Japanese Participants With Relapsed or Refractory Follicular Lymphoma (CITADEL-213). U.S. National Institutes of Health.
• [2] 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.
• [3] 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
• [4] 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2021
• [6] 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.
• [7] Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov. 2009 Aug;8(8):627-44.
• [8] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [9] Effective "activated PI3K syndrome"-targeted therapy with the PI3K inhibitor leniolisib. Blood. 2017 Nov 23;130(21):2307-2316.
• [10] The selective class I PI3K inhibitor CH5132799 targets human cancers harboring oncogenic PIK3CA mutations. Clin Cancer Res. 2011 May 15;17(10):3272-81.
• [11] INCB40093 is a selective PI3Kdelta inhibitor with potent antiproliferative activity against human B-cell tumors.