Details of the Drug

General Information of Drug (ID: DMM9F25)

• Drug Name: LDE225
• Synonyms: Erismodegib

Indication

Disease Entry	ICD 11	Status	REF
Basal cell carcinoma	2C32	Approved	[1]
Medulloblastoma	2A00.10	Phase 2	[2]
Skin cancer	2C30-2C37	Phase 2	[3]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw); 485.5
  Logarithm of the Partition Coefficient (xlogp); 5.8
  Rotatable Bond Count (rotbonds); 5
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 8
• ADMET Property:
  Half-life: The concentration or amount of drug in body reduced by one-half in 28 days [4]
  Metabolism: The drug is metabolized via oxidation and amide hydrolysis []
  Vd: The volume of distribution (Vd) of drug is 9166 L []
• Chemical Identifiers:
  Formula: C26H26F3N3O3
  IUPAC Name: N-[6-[(2S,6R)-2,6-dimethylmorpholin-4-yl]pyridin-3-yl]-2-methyl-3-[4-(trifluoromethoxy)phenyl]benzamide
  Canonical SMILES: C[C@@H]1CN(C[C@@H](O1)C)C2=NC=C(C=C2)NC(=O)C3=CC=CC(=C3C)C4=CC=C(C=C4)OC(F)(F)F
  InChI: InChI=1S/C26H26F3N3O3/c1-16-14-32(15-17(2)34-16)24-12-9-20(13-30-24)31-25(33)23-6-4-5-22(18(23)3)19-7-10-21(11-8-19)35-26(27,28)29/h4-13,16-17H,14-15H2,1-3H3,(H,31,33)/t16-,17+
  InChIKey: VZZJRYRQSPEMTK-CALCHBBNSA-N
• Cross-matching ID:
  PubChem CID: 24775005
  ChEBI ID: CHEBI:90863
  CAS Number: 956697-53-3
  DrugBank ID: DB09143
  TTD ID: D09BNZ
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Smoothened homolog (SMO)	TT8J1S3	SMO_HUMAN	Modulator	[5]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
N-myc proto-oncogene protein (MYCN)	OTWD33K1	MYCN_HUMAN	Drug Response	[6]
Suppressor of fused homolog (SUFU)	OT0IRYG1	SUFU_HUMAN	Drug Response	[6]
Zinc finger protein GLI2 (GLI2)	OTIRV97L	GLI2_HUMAN	Drug Response	[6]

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from LDE225 (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Ivosidenib	DM8S6T7	Moderate	Increased metabolism of LDE225 caused by Ivosidenib mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[7]
Arn-509	DMT81LZ	Major	Increased metabolism of LDE225 caused by Arn-509 mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[7]
Troleandomycin	DMUZNIG	Major	Decreased metabolism of LDE225 caused by Troleandomycin mediated inhibition of CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[7]
Pexidartinib	DMS2J0Z	Major	Increased metabolism of LDE225 caused by Pexidartinib mediated induction of CYP450 enzyme.	Bone/articular cartilage neoplasm [2F7B]	[7]
Tucatinib	DMBESUA	Major	Decreased metabolism of LDE225 caused by Tucatinib mediated inhibition of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[7]
Lumacaftor	DMCLWDJ	Major	Increased metabolism of LDE225 caused by Lumacaftor mediated induction of CYP450 enzyme.	Cystic fibrosis [CA25]	[8]
MK-8228	DMOB58Q	Major	Decreased metabolism of LDE225 caused by MK-8228 mediated inhibition of CYP450 enzyme.	Cytomegaloviral disease [1D82]	[7]
Eslicarbazepine	DMZREFQ	Moderate	Increased metabolism of LDE225 caused by Eslicarbazepine mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[7]
Tazemetostat	DMWP1BH	Moderate	Increased metabolism of LDE225 caused by Tazemetostat mediated induction of CYP450 enzyme.	Follicular lymphoma [2A80]	[7]
Berotralstat	DMWA2DZ	Major	Decreased metabolism of LDE225 caused by Berotralstat mediated inhibition of CYP450 enzyme.	Innate/adaptive immunodeficiency [4A00]	[7]
PF-06463922	DMKM7EW	Major	Increased metabolism of LDE225 caused by PF-06463922 mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[7]
Selpercatinib	DMZR15V	Moderate	Decreased metabolism of LDE225 caused by Selpercatinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[7]
IPI-145	DMWA24P	Major	Decreased metabolism of LDE225 caused by IPI-145 mediated inhibition of CYP450 enzyme.	Mature B-cell leukaemia [2A82]	[7]
Arry-162	DM1P6FR	Moderate	Decreased clearance of LDE225 due to the transporter inhibition by Arry-162.	Melanoma [2C30]	[9]
Ubrogepant	DM749I3	Moderate	Decreased clearance of LDE225 due to the transporter inhibition by Ubrogepant.	Migraine [8A80]	[10]
Rimegepant	DMHOAUG	Moderate	Decreased clearance of LDE225 due to the transporter inhibition by Rimegepant.	Migraine [8A80]	[11]
Fedratinib	DM4ZBK6	Major	Decreased metabolism of LDE225 caused by Fedratinib mediated inhibition of CYP450 enzyme.	Myeloproliferative neoplasm [2A20]	[7]
Entrectinib	DMMPTLH	Moderate	Decreased metabolism of LDE225 caused by Entrectinib mediated inhibition of CYP450 enzyme.	Non-small cell lung cancer [2C25]	[7]
Rucaparib	DM9PVX8	Moderate	Decreased metabolism of LDE225 caused by Rucaparib mediated inhibition of CYP450 enzyme.	Ovarian cancer [2C73]	[7]
Abametapir	DM2RX0I	Moderate	Decreased metabolism of LDE225 caused by Abametapir mediated inhibition of CYP450 enzyme.	Pediculosis [1G00]	[12]
Lefamulin	DME6G97	Moderate	Decreased metabolism of LDE225 caused by Lefamulin mediated inhibition of CYP450 enzyme.	Pneumonia [CA40]	[13]
Voxelotor	DMCS6M5	Moderate	Decreased metabolism of LDE225 caused by Voxelotor mediated inhibition of CYP450 enzyme.	Sickle-cell disorder [3A51]	[7]
Telotristat ethyl	DMDIYFZ	Moderate	Increased metabolism of LDE225 caused by Telotristat ethyl mediated induction of CYP450 enzyme.	Small intestine developmental anomaly [DA90]	[14]
Larotrectinib	DM26CQR	Moderate	Decreased metabolism of LDE225 caused by Larotrectinib mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[7]
LEE011	DMMX75K	Major	Decreased metabolism of LDE225 caused by LEE011 mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[7]
Fostamatinib	DM6AUHV	Moderate	Decreased metabolism of LDE225 caused by Fostamatinib mediated inhibition of CYP450 enzyme.	Thrombocytopenia [3B64]	[15]
Lusutrombopag	DMH6IKO	Moderate	Decreased clearance of LDE225 due to the transporter inhibition by Lusutrombopag.	Thrombocytopenia [3B64]	[16]
Elagolix	DMB2C0E	Moderate	Increased metabolism of LDE225 caused by Elagolix mediated induction of CYP450 enzyme.	Uterine fibroid [2E86]	[7]

References

• [1] The 12-month analysis from Basal Cell Carcinoma Outcomes with LDE225 Treatment (BOLT): A phase II, randomized, double-blind study of sonidegib in patients with advanced basal cell carcinoma. J Am Acad Dermatol. 2016 Jul;75(1):113-125.e5.
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] 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: 8199).
• [4] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [5] Inhibition of Hedgehog signalling by NVP-LDE225 (Erismodegib) interferes with growth and invasion of human renal cell carcinoma cells. Br J Cancer. 2014 Sep 9;111(6):1168-79.
• [6] Epigenetic targeting of Hedgehog pathway transcriptional output through BET bromodomain inhibition. Nat Med. 2014 Jul;20(7):732-40. doi: 10.1038/nm.3613. Epub 2014 Jun 29.
• [7] Product Information. Odomzo (sonidegib). Novartis Pharmaceuticals, East Hanover, NJ.
• [8] Patel S, Robinson R, Burk M "Hypertensive crisis associated with St. John's Wort." Am J Med 112 (2002): 507-8. [PMID: 11959071]
• [9] Cerner Multum, Inc. "Australian Product Information.".
• [10] Product Information. Ubrelvy (ubrogepant). Allergan Inc, Irvine, CA.
• [11] Product Information. Nurtec ODT (rimegepant). Biohaven Pharmaceuticals, New Haven, CT.
• [12] Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
• [13] Product Information. Xenleta (lefamulin). Nabriva Therapeutics US, Inc., King of Prussia, PA.
• [14] Cerner Multum, Inc. "UK Summary of Product Characteristics.".
• [15] Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.
• [16] EMA. European Medicines Agency. European Union "EMA - List of medicines under additional monitoring.".