Details of the Drug

General Information of Drug (ID: DMWAD93)

• Drug Name: Leniolisib
• Synonyms: 1354690-24-6; Leniolisib free base; UNII-L22772Z9CP; (S)-1-(3-((6-(6-methoxy-5-(trifluoromethyl)pyridin-3-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)amino)pyrrolidin-1-yl)propan-1-one; L22772Z9CP; 1354690-24-6 (free base); leniolisib(CDZ 173); CDZ173; CDZ-173; 1-[(3S)-3-[[6-[6-methoxy-5-(trifluoromethyl)pyridin-3-yl]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-4-yl]amino]pyrrolidin-1-yl]propan-1-one; Leniolisib [INN]; Leniolisib (CDZ173); Leniolisib; CDZ173; Leniolisib (USAN/INN); CDZ173-NX; SCHEMBL323054; GTPL9424; CHEMBL3643413; BDBM118299; EX-A2854; MFCD30470232; s8752; ZB1510; CS-7524; DC22326; SB18839; Example 67 [WO2012004299]; 1-{(S)-3-[6-(6-methoxy-5-trifluoromethyl-pyridin-3-yl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-4-y; 1-{(S)-3-[6-(6-methoxy-5-trifluoromethyl-pyridin-3-yl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-4-ylamino]-pyrrolidin-1-yl}-propan-1-one; AS-56217; HY-17635; A16796; D11158; US8653092, 67; Q27282602; 1-Propanone, 1-((3S)-3-((5,6,7,8-tetrahydro-6-(6-methoxy-5-(trifluoromethyl)-3-pyridinyl)pyrido(4,3-d)pyrimidin-4-yl)amino)-1-pyrrolidinyl)-; 9NQ

Indication

Disease Entry	ICD 11	Status	REF
Sjogren syndrome	4A43.20	Phase 2	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 450.5
  Topological Polar Surface Area (xlogp); 2.5
  Rotatable Bond Count (rotbonds); 5
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 10
• Chemical Identifiers:
  Formula: C21H25F3N6O2
  IUPAC Name: 1-[(3S)-3-[[6-[6-methoxy-5-(trifluoromethyl)pyridin-3-yl]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-4-yl]amino]pyrrolidin-1-yl]propan-1-one
  Canonical SMILES: CCC(=O)N1CC[C@@H](C1)NC2=NC=NC3=C2CN(CC3)C4=CC(=C(N=C4)OC)C(F)(F)F
  InChI: InChI=1S/C21H25F3N6O2/c1-3-18(31)30-6-4-13(10-30)28-19-15-11-29(7-5-17(15)26-12-27-19)14-8-16(21(22,23)24)20(32-2)25-9-14/h8-9,12-13H,3-7,10-11H2,1-2H3,(H,26,27,28)/t13-/m0/s1
  InChIKey: MWKYMZXCGYXLPL-ZDUSSCGKSA-N
• Cross-matching ID:
  PubChem CID: 57495353
  CAS Number: 1354690-24-6
  DrugBank ID: DB16217
  TTD ID: DGO2C1

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: Sjogren syndrome
• ICD Disease Classification: 4A43.20

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 (NCT02775916) Safety, Pharmacokinetics, and Preliminary Efficacy Study of CDZ173 in Patients With Primary Sjogren's Syndrome. U.S. National Institutes of Health.
• [2] Effective "activated PI3K syndrome"-targeted therapy with the PI3K inhibitor leniolisib. Blood. 2017 Nov 23;130(21):2307-2316.
• [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] 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.
• [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.