This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Name
Lonafarnib
Accession Number
DB06448
Type
Small Molecule
Groups
Investigational
Description
Not Available
Structure
Thumb
Synonyms
  • Lonafarnib
  • Lonafarnibum
External IDs
SCH 66336 / SCH-66336 / SCH66336
International/Other Brands
Sarasar
Categories
UNII
IOW153004F
CAS number
193275-84-2
Weight
Average: 638.822
Monoisotopic: 636.050229257
Chemical Formula
C27H31Br2ClN4O2
InChI Key
DHMTURDWPRKSOA-RUZDIDTESA-N
InChI
InChI=1S/C27H31Br2ClN4O2/c28-20-12-19-2-1-18-13-21(30)14-22(29)24(18)25(26(19)32-15-20)17-5-9-33(10-6-17)23(35)11-16-3-7-34(8-4-16)27(31)36/h12-17,25H,1-11H2,(H2,31,36)/t25-/m1/s1
IUPAC Name
4-(2-{4-[(2R)-6,15-dibromo-13-chloro-4-azatricyclo[9.4.0.0³,⁸]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-yl]piperidin-1-yl}-2-oxoethyl)piperidine-1-carboxamide
SMILES
NC(=O)N1CCC(CC(=O)N2CCC(CC2)[C@H]2C3=C(CCC4=C2C(Br)=CC(Cl)=C4)C=C(Br)C=N3)CC1

Pharmacology

Indication

Investigated for use/treatment in solid tumors, leukemia (unspecified), and lung cancer.

Pharmacodynamics
Not Available
Mechanism of action
TargetActionsOrganism
UProtein farnesyltransferase/geranylgeranyltransferase type-1 subunit alphaNot AvailableHumans
UInsulin-like growth factor-binding protein 3Not AvailableHumans
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Not Available
Food Interactions
Not Available

References

General References
Not Available
External Links
PubChem Compound
148195
ChemSpider
130645
BindingDB
14459
ChEBI
47097
ChEMBL
CHEMBL298734
ZINC
ZINC000003950115
PharmGKB
PA166129466
PDBe Ligand
336
Wikipedia
Lonafarnib
PDB Entries
1o5m

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentMalignant Supratentorial Neoplasm / Recurrent Glioblastoma / Recurrent Gliosarcoma1
1CompletedTreatmentAnaplastic Astrocytoma (AA) / Glioblastomas / Gliosarcoma1
1CompletedTreatmentBrain and Central Nervous System Tumors1
1CompletedTreatmentBreast Cancer1
1CompletedTreatmentCancer of Head and Neck / Squamous Cell Carcinoma (SCC)1
1CompletedTreatmentMalignant Lymphomas / Unspecified Adult Solid Tumor, Protocol Specific1
1CompletedTreatmentChronic Chronic myelogenous leukemia1
1TerminatedTreatmentBreast Cancer / Carcinoma, Colorectal / Lung Cancers / Prostate Cancer / Soft Tissue Sarcoma (STS)1
1TerminatedTreatmentHead and Neck Carcinoma2
1Unknown StatusTreatmentBrain and Central Nervous System Tumors1
1WithdrawnTreatmentColorectal Cancers / Metastatic Cancers1
1, 2RecruitingTreatmentProgeria1
1, 2TerminatedTreatmentBreast Cancer / Lung Cancers / Malignant Neoplasm of Stomach / Ovarian Cancer / Prostate Cancer1
2Active Not RecruitingTreatmentHepatitis D / Liver Diseases1
2CompletedTreatmentBreast Cancer1
2CompletedTreatmentCancer, Bladder / Transitional Cell Cancer of the Renal Pelvis and Ureter / Urethral Cancer1
2CompletedTreatmentChronic Delta Hepatitis1
2CompletedTreatmentChronic Hepatitis D Infection2
2CompletedTreatmentGlioblastoma Multiforme (GBM)1
2CompletedTreatmentHepatitis D2
2CompletedTreatmentHutchinson-Gilford Syndrome / Progeria2
2CompletedTreatmentOvarian Epithelial Cancer1
2CompletedTreatmentChronic Chronic myelogenous leukemia1
2Enrolling by InvitationTreatmentProgeria1
2Not Yet RecruitingTreatmentChronic Delta Hepatitis1
2TerminatedTreatmentMetastatic Breast Cancer1
2WithdrawnTreatmentLiver Cancer1
3RecruitingTreatmentHepatitis Delta Virus1
3TerminatedTreatmentLeukemia, Myelomonocytic, Chronic / Myelodysplasia / Myelodysplastic Syndromes / Myelomonocytic1
3TerminatedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / Neoplasm Metastases1
Not AvailableAvailableNot AvailableHGPS / Progeria1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.000829 mg/mLALOGPS
logP5.34ALOGPS
logP4.74ChemAxon
logS-5.9ALOGPS
pKa (Strongest Acidic)15.75ChemAxon
pKa (Strongest Basic)3.28ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area79.53 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity149.31 m3·mol-1ChemAxon
Polarizability60.09 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9971
Blood Brain Barrier+0.9837
Caco-2 permeable-0.6451
P-glycoprotein substrateSubstrate0.6145
P-glycoprotein inhibitor IInhibitor0.8218
P-glycoprotein inhibitor IINon-inhibitor0.7588
Renal organic cation transporterInhibitor0.6161
CYP450 2C9 substrateNon-substrate0.849
CYP450 2D6 substrateNon-substrate0.6877
CYP450 3A4 substrateSubstrate0.5869
CYP450 1A2 substrateNon-inhibitor0.6897
CYP450 2C9 inhibitorNon-inhibitor0.6924
CYP450 2D6 inhibitorNon-inhibitor0.8235
CYP450 2C19 inhibitorInhibitor0.5078
CYP450 3A4 inhibitorInhibitor0.5372
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.776
Ames testNon AMES toxic0.6428
CarcinogenicityNon-carcinogens0.9177
BiodegradationNot ready biodegradable0.9858
Rat acute toxicity2.6286 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7635
hERG inhibition (predictor II)Inhibitor0.8517
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as benzocycloheptapyridines. These are aromatic compounds containing a benzene ring and a pyridine ring fused to a seven membered carbocycle.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzocycloheptapyridines
Sub Class
Not Available
Direct Parent
Benzocycloheptapyridines
Alternative Parents
Piperidinecarboxamides / N-acylpiperidines / Pyridines and derivatives / Aryl bromides / Aryl chlorides / Benzenoids / Tertiary carboxylic acid amides / Heteroaromatic compounds / Ureas / Azacyclic compounds
show 7 more
Substituents
Benzocycloheptapyridine / N-acyl-piperidine / Piperidinecarboxamide / 1-piperidinecarboxamide / Aryl bromide / Aryl chloride / Aryl halide / Benzenoid / Pyridine / Piperidine
show 19 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Rab geranylgeranyltransferase activity
Specific Function
Essential subunit of both the farnesyltransferase and the geranylgeranyltransferase complex. Contributes to the transfer of a farnesyl or geranylgeranyl moiety from farnesyl or geranylgeranyl dipho...
Gene Name
FNTA
Uniprot ID
P49354
Uniprot Name
Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha
Molecular Weight
44408.32 Da
References
  1. Lee HY, Moon H, Chun KH, Chang YS, Hassan K, Ji L, Lotan R, Khuri FR, Hong WK: Effects of insulin-like growth factor binding protein-3 and farnesyltransferase inhibitor SCH66336 on Akt expression and apoptosis in non-small-cell lung cancer cells. J Natl Cancer Inst. 2004 Oct 20;96(20):1536-48. [PubMed:15494604]
  2. Medeiros BC, Landau HJ, Morrow M, Lockerbie RO, Pitts T, Eckhardt SG: The farnesyl transferase inhibitor, tipifarnib, is a potent inhibitor of the MDR1 gene product, P-glycoprotein, and demonstrates significant cytotoxic synergism against human leukemia cell lines. Leukemia. 2007 Apr;21(4):739-46. Epub 2007 Feb 1. [PubMed:17268526]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Protein tyrosine phosphatase activator activity
Specific Function
IGF-binding proteins prolong the half-life of the IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs on cell culture. They alter the interaction of IGF...
Gene Name
IGFBP3
Uniprot ID
P17936
Uniprot Name
Insulin-like growth factor-binding protein 3
Molecular Weight
31673.87 Da
References
  1. Lee HY, Moon H, Chun KH, Chang YS, Hassan K, Ji L, Lotan R, Khuri FR, Hong WK: Effects of insulin-like growth factor binding protein-3 and farnesyltransferase inhibitor SCH66336 on Akt expression and apoptosis in non-small-cell lung cancer cells. J Natl Cancer Inst. 2004 Oct 20;96(20):1536-48. [PubMed:15494604]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Wang E, Casciano CN, Clement RP, Johnson WW: The farnesyl protein transferase inhibitor SCH66336 is a potent inhibitor of MDR1 product P-glycoprotein. Cancer Res. 2001 Oct 15;61(20):7525-9. [PubMed:11606389]
  2. Wang EJ, Johnson WW: The farnesyl protein transferase inhibitor lonafarnib (SCH66336) is an inhibitor of multidrug resistance proteins 1 and 2. Chemotherapy. 2003 Dec;49(6):303-8. doi: 10.1159/000074531. [PubMed:14671431]

Drug created on March 19, 2008 10:33 / Updated on June 12, 2020 10:52

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