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Tipifarnib

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Also known as NSC-702818R-11577R-115777R115777ZarnestraSID137275907TIPIFARNIB (ZARNESTRA)TipifarnibÊTipifarnibÂC0088795

Summary

Tipifarnib (CHEMBL289228) is a phase-3 clinical-stage small-molecule antineoplastic agent targeting FNTB; indicated across 47 conditions including myelodysplastic syndrome and acute myeloid leukemia; with CIViC clinical evidence for 3 variant-indication associations (e.g. HRAS Mutation in bladder urothelial carcinoma).

At a glance

  • Status: Max clinical phase 3 (not approved)
  • Modality: Small molecule
  • Targets: 1 (FNTB)
  • Indications: 47 conditions
  • Clinical trials: 84
  • Precision-oncology evidence (CIViC): 3 variant–indication associations
  • Chemistry: C27H22Cl2N4O

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL289228
NameTipifarnib
TypeSmall molecule
Max phase3
ChEBICHEBI:141969
Molecular formulaC27H22Cl2N4O
InChIKeyPLHJCIYEEKOWNM-HHHXNRCGSA-N

SMILES: Cn1cncc1[C@@](N)(c1ccc(Cl)cc1)c1ccc2c(c1)c(-c1cccc(Cl)c1)cc(=O)n2C

ChEBI definition: A quinolone that is 1-methylquinolin-2-one which carries a 3-chlorophenyl and an amino(4-chlorophenyl)(1-methyl-imidazol-5-yl)methyl groups at the 4 and 6 positions, respectively (the R-isomer).

Pharmacological roles (ChEBI): antineoplastic agent, EC 2.5.1.58 (protein farnesyltransferase) inhibitor, apoptosis inducer.

Also known as: NSC-702818, R-11577, R-115777, R115777, Tipifarnib, Zarnestra, tipifarnib, TIPIFARNIB, SID137275907, TIPIFARNIB (ZARNESTRA), TipifarnibÊ, Tipifarnib (Zarnestra)

Patent coverage: 5,234 distinct patent families (18,804 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 15,448 (82%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

GeneTargetActionpAffinityCancer dependencyUniProt
FNTBfarnesyltransferase, CAAX box, subunit betaInhibition9.0790%P49356

Broader ChEMBL bioactivity targets: 6 (assay-derived). Sample: Protein farnesyltransferase, Geranylgeranyl transferase type I, Protein farnesyltransferase, Protein farnesyltransferase, Geranylgeranyl transferase type I, Cytochrome P450 3A4.

Bioactivity

ChEMBL activities: 24 potent at pChembl ≥ 5 of 24 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
P297029.24IC500.57nMCHEMBL_ACT_1227325
P297029.19IC500.65nMCHEMBL_ACT_1452754
P297029.19IC500.65nMCHEMBL_ACT_1453686
P297029.19IC500.65nMCHEMBL_ACT_1499221
FNTA9.1IC500.8nMCHEMBL_ACT_787059
FNTA9.07IC500.86nMCHEMBL_ACT_94742
FNTA9.05IC500.9nMCHEMBL_ACT_111608
FNTA9.05IC500.9nMCHEMBL_ACT_1277333
FNTA9.05IC500.9nMCHEMBL_ACT_14546336
FNTA9.05IC500.9nMCHEMBL_ACT_432268
Q612398.8EC501.6nMCHEMBL_ACT_1452756
Q612398.8EC501.6nMCHEMBL_ACT_1453688
Q612398.8EC501.6nMCHEMBL_ACT_1522943
FNTA8.52IC503nMCHEMBL_ACT_13972140
FNTA8.1IC507.9nMCHEMBL_ACT_18483974
Q612397EC50100nMCHEMBL_ACT_1523048
P297025.96IC501100nMCHEMBL_ACT_1452755
P297025.96IC501100nMCHEMBL_ACT_1453687
P297025.96IC501100nMCHEMBL_ACT_1499222
P297025.96IC501100nMCHEMBL_ACT_1522942
CYP3A45.77IC501700nMCHEMBL_ACT_2610833
CYP3A45.39IC504060nMCHEMBL_ACT_3299975
FNTA5IC5010000nMCHEMBL_ACT_1277335
FNTA5IC5010000nMCHEMBL_ACT_787061

Target pathways

Aggregated over 1 target gene(s): FNTB.

Top Reactome pathways

4 total, by targets touching each:

PathwayTargetsGenes
Inactivation, recovery and regulation of the phototransduction cascade1FNTB
RAS processing1FNTB
Potential therapeutics for SARS1FNTB
GBP-mediated host defense1FNTB

Dominant GO biological processes

GO termTargets
lipid metabolic process1
positive regulation of cell population proliferation1
protein farnesylation1
positive regulation of cell cycle1
regulation of microtubule-based movement1
prenylation1

Indications & clinical

Indications

47 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

IndicationTrial phaseMONDOEFO
myelodysplastic syndrome3MONDO:0018881EFO:0000198
acute myeloid leukemia3MONDO:0018874EFO:0000222
acute myelomonocytic leukemia M43MONDO:0018871EFO:0000223
acute myeloblastic leukemia without maturation3MONDO:0005224EFO:0003027
acute myeloblastic leukemia with maturation3MONDO:0020320EFO:0003028
adult acute monocytic leukemia3MONDO:0000875EFO:1001933
B-cell chronic lymphocytic leukemia2MONDO:0004948EFO:0000095
melanoma2MONDO:0005105EFO:0000756
exocrine pancreatic carcinoma2MONDO:0005192EFO:0002618
gliosarcoma2MONDO:0016681EFO:1001465
chronic myelomonocytic leukemia2MONDO:0020311EFO:1001779
mantle cell lymphoma2MONDO:0018876EFO:1001469
breast carcinoma2MONDO:0004989EFO:0000305
essential thrombocythemia2MONDO:0005029EFO:0000479
glioblastoma2MONDO:0018177EFO:0000519
acquired polycythemia vera2MONDO:0009891EFO:0002429
primary myelofibrosis2MONDO:0009692EFO:0002430
medulloblastoma2MONDO:0007959EFO:0002939
non-small cell lung carcinoma2MONDO:0005233EFO:0003060
breast neoplasm2MONDO:0021100EFO:0003869
primitive neuroectodermal tumor2MONDO:0005462EFO:0005235
juvenile myelomonocytic leukemia2MONDO:0011908EFO:1000309
inflammatory breast carcinoma2MONDO:0006804EFO:1000984
urothelial carcinoma2MONDO:0040679EFO:0008528
lung neoplasm2MONDO:0021117MONDO:0008903
astrocytoma (excluding glioblastoma)2MONDO:0019781MONDO:0021633
head and neck squamous cell carcinoma2MONDO:0010150EFO:0000181
peripheral T-cell lymphoma, not otherwise specified2MONDO:0004964EFO:0000211
paraganglioma2MONDO:0000448EFO:1000453
oligodendroglioma2MONDO:0016695MONDO:0002540
colorectal neoplasm2MONDO:0005335MONDO:0005575
chronic myeloid leukemia1MONDO:0011996EFO:0000339
leukemia1MONDO:0005059EFO:0000565
neoplasm1MONDO:0005070EFO:0000616
plasma cell myeloma1MONDO:0009693EFO:0001378
male breast carcinoma1MONDO:0005628EFO:0006861
myeloproliferative neoplasm1MONDO:0020076EFO:0002428
central nervous system neoplasm1MONDO:0006130EFO:1000158
brain neoplasm1MONDO:0021211EFO:0003833

8 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 84.

Phase distribution

PhaseTrials
PHASE246
PHASE123
PHASE1/PHASE211
PHASE32
PHASE2/PHASE31
Not specified1

Top trials by phase / activity

NCTPhaseStatusTitle
NCT00093470PHASE3COMPLETEDTipifarnib in Treating Patients With Acute Myeloid Leukemia in Remission
NCT00093990PHASE3COMPLETEDTipifarnib Versus Best Supportive Care in the Treatment of Newly Diagnosed Acute Myeloid Leukemia (AML)
NCT00454480PHASE2/PHASE3COMPLETEDCombination Chemotherapy With or Without Gemtuzumab Ozogamicin or Tipifarnib in Treating Patients With Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndromes
NCT03155620PHASE2ACTIVE_NOT_RECRUITINGTargeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)
NCT04284774PHASE2ACTIVE_NOT_RECRUITINGTipifarnib for the Treatment of Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With HRAS Gene Alterations, a Pediatric MATCH Treatment Trial
NCT06540963PHASE2RECRUITINGTipifarnib and Naxitamab for Relapsed/Refractory Neuroblastoma
NCT00005041PHASE2COMPLETEDR115777 in Treating Patients With Relapsed Small Cell Lung Cancer
NCT00005832PHASE2COMPLETEDS9924 R115777 in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer
NCT00005833PHASE2COMPLETEDS9923 R115777 in Treating Patients With Advanced Colorectal Cancer
NCT00005843PHASE2COMPLETEDR115777 in Treating Patients Who Have Metastatic Pancreatic Cancer
NCT00005848PHASE2COMPLETEDR115777 in Treating Patients With Progressive, Metastatic Prostate Cancer That Has Not Responded to Hormone Therapy
NCT00005859PHASE1/PHASE2COMPLETEDTipifarnib in Treating Patients With Recurrent or Progressive Malignant Glioma
NCT00005989PHASE2COMPLETEDR115777 in Treating Patients With Recurrent or Metastatic Non-small Cell Lung Cancer
NCT00006376PHASE2COMPLETEDR115777 in Treating Patients With Advanced Bladder Cancer
NCT00021541PHASE2COMPLETEDR115777 to Treat Children With Neurofibromatosis Type 1 and Progressive Plexiform Neurofibromas
NCT00025038PHASE2COMPLETEDCombination Chemotherapy Followed By Donor Bone Marrow or Umbilical Cord Blood Transplant in Treating Children With Newly Diagnosed Juvenile Myelomonocytic Leukemia
NCT00026104PHASE2COMPLETEDCombination Chemotherapy Plus Radiation Therapy With or Without Tipifarnib in Treating Patients With Locally Advanced Pancreatic Cancer
NCT00027872PHASE2COMPLETEDTipifarnib in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia
NCT00045396PHASE2COMPLETEDA Phase II Study Of The Farnesyltransferase Inhibitor ZANESTRA (R115777, NSC #702818, IND #58,359) In Complete Remission Following Induction And/Or Consolidation Chemotherapy In Adults With Poor-Risk Acute Myelogenous Leukemia (AML) And High-Risk Myelodysplasia (MDS)
NCT00047190PHASE2COMPLETEDTipifarnib in Treating Patients With Myelofibrosis and Myeloid Metaplasia
NCT00047216PHASE2COMPLETEDTipifarnib in Treating Patients With Recurrent Bladder Cancer
NCT00048503PHASE2COMPLETEDStudy of Tipifarnib as Postconsolidation Therapy for Acute Myeloid Leukemia in Patients 60 Years and Older
NCT00049114PHASE2COMPLETEDTipifarnib, Doxorubicin, and Cyclophosphamide in Treating Women With Locally Advanced Breast Cancer
NCT00050141PHASE2COMPLETEDStudy of Letrozole Plus Tipifarnib or Placebo in the Treatment of Advanced Breast Cancer
NCT00050154PHASE2COMPLETEDStudy of Tipifarnib in Patients With High-Risk Myelodysplastic Syndrome (MDS)
NCT00050986PHASE1/PHASE2COMPLETEDPhase I/II Evaluation of Temozolomide and ZARNESTRA (R115777) for Recurrent and Progressive Glioblastoma Multiforme
NCT00052728PHASE2COMPLETEDTipifarnib Plus Tamoxifen in Treating Women With Metastatic Breast Cancer
NCT00054470PHASE2WITHDRAWNTipifarnib Plus Trastuzumab in Treating Patients With Metastatic Breast Cancer
NCT00055757PHASE2COMPLETEDTipifarnib, Gemcitabine, and Cisplatin in Treating Patients With Stage III or Stage IV Non-Small Cell Lung Cancer
NCT00058097PHASE2COMPLETEDTipifarnib and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme
NCT00060125PHASE2COMPLETEDTipifarnib in Treating Patients With Metastatic Malignant Melanoma
NCT00070252PHASE1/PHASE2COMPLETEDNeoadjuvant Tipifarnib, Docetaxel, and Capecitabine in Treating Patients With Locally Advanced or Metastatic Solid Tumors or Stage IIIA or Stage IIIB Breast Cancer
NCT00070525PHASE2COMPLETEDTipifarnib in Treating Young Patients With Recurrent or Progressive High-Grade Glioma, Medulloblastoma, Primitive Neuroectodermal Tumor, or Brain Stem Glioma
NCT00077363PHASE2COMPLETEDCapecitabine and Tipifarnib in Treating Women With Taxane-Resistant Metastatic Breast Cancer
NCT00079339PHASE1/PHASE2COMPLETEDTipifarnib and Radiation Therapy in Treating Young Patients With Brainstem Glioma
NCT00082810PHASE2COMPLETEDTipifarnib and Fulvestrant in Hormone Receptor-Positive Metastatic Breast Cancer
NCT00082888PHASE2COMPLETEDTipifarnib in Treating Patients With Relapsed or Refractory Lymphoma
NCT00093418PHASE2COMPLETEDS0432 Tipifarnib in Treating Older Patients With Acute Myeloid Leukemia
NCT00096122PHASE1/PHASE2COMPLETEDIdarubicin, Cytarabine, and Tipifarnib in Treating Patients With Newly Diagnosed Myelodysplastic Syndromes or Acute Myeloid Leukemia
NCT00100750PHASE1/PHASE2COMPLETEDTipifarnib and Gemcitabine Hydrochloride in Treating Women With Metastatic Breast Cancer

Clinical evidence (CIViC)

Variant × indication × effect (3 predictive associations from 3 curated evidence items):

VariantIndicationEffectTherapyLevelCIViC
HRAS MutationBladder Urothelial CarcinomaSensitivity/ResponseTipifarnibCIViC BEID9632
HRAS MutationHead And Neck Squamous Cell CarcinomaSensitivity/ResponseTipifarnibCIViC BEID9633
NF1 MutationNeurofibromaSensitivity/ResponseTipifarnibCIViC BEID7426

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

2 molecules share ≥1 primary target. Top 2 by shared-target count:

MoleculeSourceStatusShared targets
CORTISONEChEMBLPhase 4 (approved)FNTB
LONAFARNIBChEMBLPhase 4 (approved)FNTB

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 30

This page pulls from 30 datasets indexed by BioBTree:

chebichembl_activitychembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsdepmapefoensemblentrezgogoparentgtopdbgtopdb_interactiongtopdb_ligandhgncmeshmondomsigdbpatent_compoundpharmgkbpharmgkb_guidelinepubchempubchem_activityreactomereactomeparentrefseqtranscriptuniprot