Details of the Drug

General Information of Drug (ID: DMBNI20)

• Drug Name: Ulipristal
• Synonyms: Ella (TN)

Indication

Disease Entry	ICD 11	Status	REF
Contraception	QA21	Approved	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 433.6
  Logarithm of the Partition Coefficient (xlogp); 2.9
  Rotatable Bond Count (rotbonds); 3
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 4
• ADMET Property:
  Absorption AUC: The area under the plot of plasma concentration (AUC) of drug is 556 +/- 260 mcgh/L []
  Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 176 +/- 89 mcg/L []
  Absorption Tmax: The time to maximum plasma concentration (Tmax) is 60-90 min []
  Clearance: The apparent oral clearance of drug is 76.8 +/- 64.0 L/h []
  Half-life: The concentration or amount of drug in body reduced by one-half in 32.4 +/- 6.3 hours [2]
  Metabolism: The drug is metabolized via the CYP3A4 and to a lesser extent by CYP1A2 into mono-demethylated (active) and di-methylated (inactive) metabolites []
• Chemical Identifiers:
  Formula: C28H35NO3
  IUPAC Name: (8S,11R,13S,14S,17R)-17-acetyl-11-[4-(dimethylamino)phenyl]-17-hydroxy-13-methyl-1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-3-one
  Canonical SMILES: CC(=O)[C@]1(CC[C@@H]2[C@@]1(C[C@@H](C3=C4CCC(=O)C=C4CC[C@@H]23)C5=CC=C(C=C5)N(C)C)C)O
  InChI: InChI=1S/C28H35NO3/c1-17(30)28(32)14-13-25-23-11-7-19-15-21(31)10-12-22(19)26(23)24(16-27(25,28)2)18-5-8-20(9-6-18)29(3)4/h5-6,8-9,15,23-25,32H,7,10-14,16H2,1-4H3/t23-,24+,25-,27-,28-/m0/s1
  InChIKey: HKDLNTKNLJPAIY-WKWWZUSTSA-N
• Cross-matching ID:
  PubChem CID: 13559281
  CAS Number: 159811-51-5
  DrugBank ID: DB08867
  TTD ID: D0V4WD
  INTEDE ID: DR1657

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Progesterone receptor (PGR)	TTUV8G9	PRGR_HUMAN	Modulator	[1]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[3]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Substrate	[4]

Molecular Expression Atlas of This Drug

• The Studied Disease: Contraception
• ICD Disease Classification: QA21

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Progesterone receptor (PGR)	DTT	PGR	3.26E-38	-3.79	-2.5
Cytochrome P450 1A2 (CYP1A2)	DME	CYP1A2	2.25E-08	-1.79E-01	-6.25E-01
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	2.20E-02	-1.08E-01	-2.31E-01

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Ulipristal (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Gilteritinib	DMTI0ZO	Moderate	Decreased clearance of Ulipristal due to the transporter inhibition by Gilteritinib.	Acute myeloid leukaemia [2A60]	[5]
Troleandomycin	DMUZNIG	Minor	Decreased metabolism of Ulipristal caused by Troleandomycin mediated inhibition of CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[5]
Pexidartinib	DMS2J0Z	Moderate	Increased metabolism of Ulipristal caused by Pexidartinib mediated induction of CYP450 enzyme.	Bone/articular cartilage neoplasm [2F7B]	[6]
Talazoparib	DM1KS78	Moderate	Decreased clearance of Ulipristal due to the transporter inhibition by Talazoparib.	Breast cancer [2C60-2C6Y]	[7]
Tucatinib	DMBESUA	Moderate	Decreased metabolism of Ulipristal caused by Tucatinib mediated inhibition of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[8]
Fidaxomicin	DMFP6MV	Minor	Decreased clearance of Ulipristal due to the transporter inhibition by Fidaxomicin.	Clostridium difficile enterocolitis [1A04]	[9]
Ripretinib	DM958QB	Moderate	Decreased clearance of Ulipristal due to the transporter inhibition by Ripretinib.	Gastrointestinal stromal tumour [2B5B]	[9]
Aliskiren	DM1BV7W	Moderate	Decreased clearance of Ulipristal due to the transporter inhibition by Aliskiren.	Hypertension [BA00-BA04]	[10]
Berotralstat	DMWA2DZ	Major	Decreased clearance of Ulipristal due to the transporter inhibition by Berotralstat.	Innate/adaptive immunodeficiency [4A00]	[11]
Naloxegol	DML0B41	Minor	Decreased clearance of Ulipristal due to the transporter inhibition by Naloxegol.	Large intestine motility disorder [DB32]	[12]
PF-06463922	DMKM7EW	Moderate	Increased metabolism of Ulipristal caused by PF-06463922 mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[13]
Selpercatinib	DMZR15V	Moderate	Decreased metabolism of Ulipristal caused by Selpercatinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[5]
GDC-0199	DMH0QKA	Major	Decreased clearance of Ulipristal due to the transporter inhibition by GDC-0199.	Mature B-cell leukaemia [2A82]	[9]
IPI-145	DMWA24P	Moderate	Decreased metabolism of Ulipristal caused by IPI-145 mediated inhibition of CYP450 enzyme.	Mature B-cell leukaemia [2A82]	[5]
Arry-162	DM1P6FR	Moderate	Decreased clearance of Ulipristal due to the transporter inhibition by Arry-162.	Melanoma [2C30]	[9]
Ubrogepant	DM749I3	Moderate	Decreased clearance of Ulipristal due to the transporter inhibition by Ubrogepant.	Migraine [8A80]	[14]
Rucaparib	DM9PVX8	Moderate	Decreased metabolism of Ulipristal caused by Rucaparib mediated inhibition of CYP450 enzyme.	Ovarian cancer [2C73]	[15]
Abametapir	DM2RX0I	Moderate	Decreased metabolism of Ulipristal caused by Abametapir mediated inhibition of CYP450 enzyme.	Pediculosis [1G00]	[16]
Lefamulin	DME6G97	Moderate	Decreased metabolism of Ulipristal caused by Lefamulin mediated inhibition of CYP450 enzyme.	Pneumonia [CA40]	[5]
Riociguat	DMXBLMP	Moderate	Decreased clearance of Ulipristal due to the transporter inhibition by Riociguat.	Pulmonary hypertension [BB01]	[9]
Telotristat ethyl	DMDIYFZ	Moderate	Increased metabolism of Ulipristal caused by Telotristat ethyl mediated induction of CYP450 enzyme.	Small intestine developmental anomaly [DA90]	[5]
LEE011	DMMX75K	Moderate	Decreased metabolism of Ulipristal caused by LEE011 mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[17]
Fostamatinib	DM6AUHV	Moderate	Decreased metabolism of Ulipristal caused by Fostamatinib mediated inhibition of CYP450 enzyme.	Thrombocytopenia [3B64]	[18]

References

• [1] Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
• [2] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [3] Emergency contraception. Gynecol Endocrinol. 2013 Mar;29 Suppl 1:1-14.
• [4] The clinical pharmacology and pharmacokinetics of ulipristal acetate for the treatment of uterine fibroids. Reprod Sci. 2015 Apr;22(4):476-83.
• [5] Cerner Multum, Inc. "UK Summary of Product Characteristics.".
• [6] Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
• [7] Product Information. Talzenna (talazoparib). Pfizer U.S. Pharmaceuticals Group, New York, NY.
• [8] Product Information. Tukysa (tucatinib). Seattle Genetics Inc, Bothell, WA.
• [9] Cerner Multum, Inc. "Australian Product Information.".
• [10] Canadian Pharmacists Association.
• [11] Product Information. Orladeyo (berotralstat). BioCryst Pharmaceuticals Inc, Durham, NC.
• [12] Product Information. Movantik (naloxegol). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
• [13] Product Information. Lorbrena (lorlatinib). Pfizer U.S. Pharmaceuticals Group, New York, NY.
• [14] Product Information. Ubrelvy (ubrogepant). Allergan Inc, Irvine, CA.
• [15] EMA. European Medicines Agency. European Union "EMA - List of medicines under additional monitoring.".
• [16] Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
• [17] DSouza DL, Levasseur LM, Nezamis J, Robbins DK, Simms L, Koch KM "Effect of alosetron on the pharmacokinetics of alprazolam." J Clin Pharmacol 41 (2001): 452-4. [PMID: 11304902]
• [18] Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.