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Compound Detail

CHEMBL298734

LONAFARNIB
💊 Approved Drug
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💊 Approved Drug
NC(=O)N1CCC(CC(=O)N2CCC([C@H]3c4ncc(Br)cc4CCc4cc(Cl)cc(Br)c43)CC2)CC1

Basic Information

ChEMBL ID CHEMBL298734
Name LONAFARNIB
Phase Approved
Structure Type MOL
InChI Key DHMTURDWPRKSOA-RUZDIDTESA-N
Therapeutic ✓ Yes

Known Names

Lonafarnib Sarasar SCH 66336 SCH-66336 SCH66336 Zokinvy
16
Targets
51
Activities
2
Assay Types
22
PK Parameters
20
Publications
6
Known Names
20
Indications
1
Mechanisms

Molecular Properties

638.8
MW (Da)
5.91
ALogP
3
HBA
1
HBD
79.5
PSA (Ų)
0.45
QED
2
Ro5 Violations
3
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 2020
Availability Prescription
Chirality Single Enantiomer

Routes of Administration

Oral

Flags

Natural Product First in Class
USAN Stem -farnib
USAN Year 2002

Extended Properties

Molecular Formula C27H31Br2ClN4O2
MW 638.83
Aromatic Rings 2
Heavy Atoms 36
NP-Likeness -0.49

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Protein farnesyltransferase inhibitor INHIBITOR Protein farnesyltransferase

Indications

Laminopathies Progeria Progeria Carcinoma, Non-Small-Cell Lung Hepatitis D Leukemia, Myelomonocytic, Chronic Myelodysplastic Syndromes Neoplasm Metastasis Breast Neoplasms Leukemia, Myelogenous, Chronic, BCR-ABL Positive Liver Neoplasms Ovarian Neoplasms Urethral Neoplasms Urinary Bladder Neoplasms Astrocytoma Central Nervous System Neoplasms Colorectal Neoplasms Glioblastoma Gliosarcoma Head and Neck Neoplasms

ATC Classification

A16AX20
lonafarnib
Level 1: ALIMENTARY TRACT AND METABOLISM
Level 2: OTHER ALIMENTARY TRACT AND METABOLISM PRODUCTS

Activity Summary

IC50 38 meas. best 8.72
EC50 13 meas. best 7.92

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Protein farnesyltransferase
CHEMBL2095197
IC50 8.72 8.72 1.9 1
Unchecked
CHEMBL612545
IC50 8.72 7.318 1.9 10
Protein farnesyltransferase
CHEMBL2094108
IC50 8.72 8.52 1.9 11
Protein farnesyltransferase
CHEMBL2095178
IC50 8.11 8.09 7.8 3
Unchecked
CHEMBL612545
EC50 7.92 7.3686 12.0 7
GTPase KRas
CHEMBL2189121
IC50 7.4 7.4 40.0 1
NIH3T3
CHEMBL614822
EC50 7.3 7.1167 50.0 3
MCF7
CHEMBL387
IC50 7.3 7.3 50.0 1
HCT-116
CHEMBL394
IC50 7.16 7.16 70.0 1
NON-PROTEIN TARGET
CHEMBL3879801
IC50 7.16 7.16 70.0 1
GTPase HRas
CHEMBL2167
IC50 7.16 7.16 70.0 1
NIH-H
CHEMBL615000
IC50 7.14 7.14 72.0 1
HCT-116
CHEMBL394
EC50 7.13 7.08 74.0 2
COS-1
CHEMBL614563
IC50 7.12 7.12 75.0 1
Protein farnesyltransferase
CHEMBL2096912
EC50 7.0 7.0 100.0 1
NIH-K
CHEMBL615001
IC50 6.3 6.3 500.0 1
ATP-dependent translocase ABCB1
CHEMBL4302
IC50 5.57 5.57 2700.0 1
SARS-CoV-2
CHEMBL4303835
IC50 5.3 5.275 4990.0 2

Pharmacokinetic Data

Parameter Value Units Species
AUC 24100.0 ng.hr.mL-1 Mus musculus
AUC 31800.0 ng.hr.mL-1 Mus musculus
AUC 41450.0 ng.hr.mL-1 Mus musculus
AUC 24100.0 ng.hr.mL-1 Mus musculus
AUC 14700.0 ng.hr.mL-1 Macaca fascicularis
AUC 24100.0 ng.hr.mL-1 Rattus norvegicus
AUC 14700.0 ng.hr.mL-1 Macaca fascicularis
Cmax 8840.0 nM Mus musculus
Cmax 20000.0 nM Mus musculus
Cmax 16600.0 nM Mus musculus
Cmax 8.84 ug Mus musculus
Cmax 1900.0 nM Macaca fascicularis
Cmax 1900.0 nM Macaca fascicularis
F 75.8 % Mus musculus
F 76.0 % Mus musculus
F 50.0 % Macaca fascicularis
F 76.0 % Rattus norvegicus
F 76.0 % Mus musculus
F 50.0 % Macaca fascicularis
T1/2 1.4 hr Mus musculus
T1/2 1.4 hr Mus musculus
T1/2 3.0 hr Macaca fascicularis

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Unchecked IC50 = 1.9 nM 8.72 Inhibition of human recombinant farnesyltransferase using [3H]geranylgeranyldiph... 34236862
Protein farnesyltransferase IC50 = 1.9 nM 8.72 Inhibition of rat brain FTase assessed as decrease in transfer of [3H]farnesyl f... 28505447
Protein farnesyltransferase IC50 = 1.9 nM 8.72 Inhibition of human recombinant FTase using [3H]farnesyldiphosphate 25530833
Protein farnesyltransferase IC50 = 1.9 nM 8.72 Inhibition of Farnesyl protein transferase 10377218
Protein farnesyltransferase IC50 = 1.9 nM 8.72 Compound ability to inhibit the transfer of [3H]- farnesyl from Farnesyltransfer... 9822558
Protein farnesyltransferase IC50 = 1.9 nM 8.72 Inhibitory activity against Hras Farnesyltransferase (FPT). 10411485
Protein farnesyltransferase IC50 = 1.9 nM 8.72 Inhibition of Protein farnesyltransferase in Cos-1 monkey kidney cells expressin... 12190309
Protein farnesyltransferase IC50 = 1.9 nM 8.72 Inhibitory concentration against farnesyltransferase was determined 15055985
Protein farnesyltransferase IC50 = 2.0 nM 8.7 Inhibition of Farnesyltransferase 14736242
Unchecked IC50 = 2.0 nM 8.7 Inhibition of [3H]-FPP incorporation into H-ras CVLS by farnesyltransferase 15501060
Protein farnesyltransferase IC50 = 2.0 nM 8.7 Inhibition of [3H]FPP incorporation into H-ras CVLS by Farnesyltransferase 15501065
Unchecked IC50 = 4.9 nM 8.31 Inhibition of recombinant human FTase incubated for 30 mins in presence of [3H]F... 16222147
Protein farnesyltransferase IC50 = 7.8 nM 8.11 In vitro inhibitory activity against farnesyltransferase (FTase) 12657284
Unchecked IC50 = 7.8 nM 8.11 Inhibition of recombinant bovine FTase incubated for 30 mins in presence of [3H]... 16222147
Protein farnesyltransferase IC50 = 8.3 nM 8.08 Inhibition of bovine farnesyltransferase 15808463
Protein farnesyltransferase IC50 = 8.3 nM 8.08 Inhibition of Bovine farnesyltransferase (FTase) 15454228
Protein farnesyltransferase IC50 = 10.0 nM 8.0 Inhibition of FTase in human COS7 cells 20925433
Unchecked IC50 = 10.0 nM 8.0 Inhibition of COS cell proliferation 15501065
Protein farnesyltransferase IC50 = 10.0 nM 8.0 Inhibiting the farnesylation of H-ras proteins in COS-7 monkey cells transiently... 9822558
Protein farnesyltransferase IC50 = 10.0 nM 8.0 Effect on Ras processing in Cos-1 monkey kidney cells expressing either H-Ras-Va... 10411485

Literature References

PubMed DOI Target Context # Activities
16222147 10.1097/00001813-200511000-00004 Unchecked 14
10411485 10.1021/jm990059k Mus musculus 7
9822558 10.1021/jm980462b Mus musculus 6
33228976 10.1016/j.ejmech.2020.113006 ADMET 4
9822558 10.1021/jm980462b Cynomolgus monkey 4
9822558 10.1021/jm980462b Unchecked 3
16222147 10.1097/00001813-200511000-00004 HCT-116 2
15454228 10.1016/j.bmcl.2004.08.012 Protein farnesyltransferase 2
15501065 10.1016/j.bmcl.2004.09.020 Protein farnesyltransferase 2
15501065 10.1016/j.bmcl.2004.09.020 Unchecked 2
15501065 10.1016/j.bmcl.2004.09.020 ADMET 2
- 10.6019/CHEMBL4651402 SARS-CoV-2 2
- 10.6019/CHEMBL4808148 Histone deacetylase 6 2
- 10.21203/rs.3.rs-23951/v1 SARS-CoV-2 2
15808463 10.1016/j.bmcl.2005.02.062 Protein farnesyltransferase 2
9822558 10.1021/jm980462b Protein farnesyltransferase 2
16222147 10.1097/00001813-200511000-00004 NIH3T3 2
10411485 10.1021/jm990059k Protein farnesyltransferase 2
- 10.6019/CHEMBL4495565 SARS-CoV-2 2
14736242 10.1021/jm030434f Protein farnesyltransferase 1

Data from ChEMBL 36 via Core Engine