Details of the Drug-Related molecule(s) Expression Atlas

General Information of Drug (ID: DMGM2Z6)

Drug Name

Lonafarnib Drug Info

Synonyms

Sarasar; Lonafarnib [USAN]; Sch 66336; Sch66336; SCH-066336; Sch-66336; Lonafarnib (USAN/INN); (+)-4-(2-(4-(11R)-3,10-Dibromo-8-chloro-6,11-dihydro-5H-benzo(5,6)cyclohepta(1,2-b)pyridin-11-yl)-piperidin-1-yl))-2-oxoethyl)-piperidine-1-carboxamide; (+)-4-(2-(4-(8-chloro-3,10-dibromo-6,11-dihydro-5H-benzo(5,6)cyclohepta(1,2-b)pyridin-11-yl)-1-piperidinyl)-2-oxoethyl)-1-piperidinecarboxamide; (+)-4[2-[4-(8-Chloro-3,10-dibromo-6,11-dihydro-5H-benzo[5,6] cyclohepta[1,2-b]-pyridin-11(R)-yl-1-piperidinyl]-2-oxo-ethyl]-1-piperidinecarboxamide; 4-(2-(4-(8-Chloro-3,10-dibromo-6,11-dihydro-5H-benzo(5,6)cyclohepta(1,2-b)pyridin-11-yl)-1-piperidinyl)-2-oxoethyl)-1-piperidinecarboxamide; 4-(2-(4-(8-Chloro-3,10-dibromo-6,11-dihydro-5H-benzo-(5,6)-cyclohepta(1,2-b)-pyridin-11(R)-yl)-1-piperidinyl)-2-oxo-ethyl)-1-piperidinecarboxamide; 4-{2-[4-(3,10-DIBROMO-8-CHLORO-6,11-DIHYDRO-5H-BENZO[5,6]CYCLOHEPTA[1,2-B]PYRIDIN-11-YL)PIPERIDIN-1-YL]-2-OXOETHYL}PIPERIDINE-1-CARBOXAMIDE

Indication

Disease Entry	ICD 11	Status	REF
Hutchinson-Gilford progeria syndrome	LD2B	Approved	[1]
Myelodysplastic syndrome	2A37	Phase 3	[2]
Hepatitis D virus infection	1E51.2	Phase 2	[3]
Non-small-cell lung cancer	2C25.Y	Discontinued in Phase 3	[4]

Therapeutic Class

Anticancer Agents

Cross-matching ID

PubChem CID: 148195
ChEBI ID: CHEBI:47097
CAS Number: CAS 193275-84-2
TTD Drug ID: DMGM2Z6
INTEDE Drug ID: DR1861
ACDINA Drug ID: D01220

Molecule(s) Related to This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Farnesyl protein transferase (Ftase)	TTXQKM3	FNTA_HUMAN; FNTB_HUMAN	Modulator	[1]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	Highest Status	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Phase 2	[5]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Phase 2	[5]

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The Expression Level of Molecule(s) in Normal Tissue of Major ADME-Related Organs

Molecule	Molecule Type	Gene Name	Liver	Colon	Kidney	Small Intestine
Farnesyl protein transferase (Ftase)	DTT	FNTB	7.914	8.13	7.856	8.107
Cytochrome P450 3A5 (CYP3A5)	DME	CYP3A5	10.08	7.207	5.403	9.211
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	11.692	6.58	4.984	9.089

Molecule Expression Atlas in Normal Tissue of Major ADME-related organs

The Expression Level of Molecule(s) between Disease Section and Healthy Individual Tissue

The Studied Disease

Hutchinson-Gilford progeria syndrome

ICD Disease Classification

LD2B

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Farnesyl protein transferase (Ftase)	DTT	FNTB; FNTA	5.43E-01	-0.1	-0.4
Cytochrome P450 3A5 (CYP3A5)	DME	CYP3A5	3.78E-02	4.07E-01	1.09E+00
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	3.90E-02	-3.45E-01	-1.49E+00

Molecular Expression Atlas between Disease Section and Healthy Individual Tissue

References

1	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
2	ClinicalTrials.gov (NCT00109538) Study of Lonafarnib Versus Placebo in Subjects With Either Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML) (Study P02978AM3)(TERMINATED). U.S. National Institutes of Health.
3	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
4	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: 8024).
5	Identification of human liver cytochrome P450 enzymes responsible for the metabolism of lonafarnib (Sarasar). Drug Metab Dispos. 2006 Apr;34(4):628-35.