Tipifarnib (R115777)

Catalog No.S1453 Synonyms: IND 58359

For research use only.

Tipifarnib (R115777, IND 58359) is a potent and specific farnesyltransferase (FTase) inhibitor with IC50 of 0.6 nM, its anti-proliferative effects are most prominent in H-ras or N-ras mutant cells. Phase 3.

Tipifarnib (R115777) Chemical Structure

CAS No. 192185-72-1

Selleck's Tipifarnib (R115777) has been cited by 30 publications

Purity & Quality Control

Choose Selective FTase Inhibitors

Biological Activity

Description Tipifarnib (R115777, IND 58359) is a potent and specific farnesyltransferase (FTase) inhibitor with IC50 of 0.6 nM, its anti-proliferative effects are most prominent in H-ras or N-ras mutant cells. Phase 3.
Features A potent and selective farnesyl protein transferase inhibitor with significant antitumor effects.
Targets
FTase [1]
()
0.6 nM
In vitro

Using Tipifarnib 5 μM for 72 hours, the percentage of apoptotic cells is significantly higher in drug-treated compared to DMSO-treated LGL T-cells. Using T-cells from healthy donors, Tipifarnib reduces the percentage of IFNγ-positive cells in a time-dependent manner. Tipifarnib reduces the amount of activated Ras in precipitates compared to DMSO. [2] Tipifarnib exerts selective in vitro toxicity against clonal MDS hematopoiesis at concentrations less than 10 nM the effect being more prominent in white cell progenitors. This action is not due to apoptosis induction as both normal and MDS progenitors displays equivalent DiOC3 and annexin V expression up to 72 hours after exposure to Tipifarnib. [3] Combining Tipifarnib with 10 nM 4-OH-tamoxifen in the presence of E2 reduces the IC50 8-fold from 400 to 50 nM. [4] Tipifarnib induces apoptosis in U937 cells. [5] In addition, Tipifarnib inhibits isolated human farnesyltransferase for a lamin B peptide and for the K-RasB peptide with IC50 of 0.86 nM and 7.9 nM, respectively. [6]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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Assay
Methods Test Index PMID
Western blot Caspase-12 / PARP1 ; Rheb / p-mTOR / mTOR / p-P70S6K / P70 S6K / p-S6 / S6 ; Bcl-2 / Bcl-xl / Mcl-1 / Bax / Bak / Puma / Noxa / Bim / Lamin B ; HDJ-2 / N-Ras / FKBP51 / p-AKT / AKT ; p-c-Raf / c-Raf / p-MEK / MEK / p-ERK / ERK 21378206 23996484 21673341
Growth inhibition assay Cell viability 26630652
In vivo Ki-67 is lower in the tumors treated with E2 withdrawal plus R115777 compared with E2 withdrawal alone. The combination of tamoxifen and R115777 results in significantly lower Ki-67 compared with either tamoxifen or R115777 alone (mean of 5% versus 16.9% and 67.3%, respectively). [4] In contrast, no significant difference in apoptotic scores is seen between the treatment groups. R115777 alone also reduces the CTI compared with control. The combination of tamoxifen and R115777 or R115777 coupled with E2 withdrawal is most effective at lowering the CTI (0.8 and 0.7, respectively), which may account for the decrease in tumor volume. [4]

Protocol (from reference)

Cell Research:[4]
  • Cell lines: MACS-selected CD34+ cells
  • Concentrations: 2.5 nM, 10 nM, 25 nM and 50 nM
  • Incubation Time: 48 hours
  • Method: MACS-selected CD34+ cells are seeded in Methocult 4435 'complete' 1% bovine serum albumin, 3 U/mL recombinant human (rh) erythropoietin, 0.1 mM 2-mercaptoethanol, 2 mM L-glutamine and the following cytokines: 50 ng/mL rh stem cell factor, 20 ng/mL rh GM-CSF, 20 ng/mL rh IL-3, 20 ng/mL rh IL-6 and 20 ng/mL h G-CSF. DMSO or Tipifarnib is added at the concentrations of 2.5, 10, 25 and 50 nM at day 1. All cultures are performed in duplicates and the numbers of colonies are scored after 14 days of incubation at 37 °C in a humidified incubator containing 5% CO2
Animal Research:[4]
  • Animal Models: Female ovariectomized Ncr foxhead nude mice
  • Dosages: 50 mg/kg
  • Administration: Oral gavage

Solubility (25°C)

In vitro

DMSO 14 mg/mL
(28.6 mM)
Water Insoluble
Ethanol Insoluble

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
15% Captisol+citrate vehicle
For best results, use promptly after mixing.

5 mg/mL

Chemical Information

Molecular Weight 489.4
Formula

C27H22Cl2N4O

CAS No. 192185-72-1
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CN1C=NC=C1C(C2=CC=C(C=C2)Cl)(C3=CC4=C(C=C3)N(C(=O)C=C4C5=CC(=CC=C5)Cl)C)N

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

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% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT04997902 Recruiting Drug: Tipifarnib|Drug: Alpelisib HNSCC Kura Oncology Inc. December 7 2021 Phase 1|Phase 2
NCT04865159 Recruiting Drug: Tipifarnib Advanced Solid Tumor Kura Oncology Inc. May 6 2021 Phase 1
NCT04284774 Recruiting Drug: Tipifarnib Recurrent Adrenal Gland Pheochromocytoma|Recurrent Ectomesenchymoma|Recurrent Ependymoma|Recurrent Ewing Sarcoma|Recurrent Hepatoblastoma|Recurrent Kidney Wilms Tumor|Recurrent Langerhans Cell Histiocytosis|Recurrent Malignant Germ Cell Tumor|Recurrent Malignant Glioma|Recurrent Medulloblastoma|Recurrent Melanoma|Recurrent Neuroblastoma|Recurrent Non-Hodgkin Lymphoma|Recurrent Osteosarcoma|Recurrent Peripheral Primitive Neuroectodermal Tumor|Recurrent Rhabdoid Tumor|Recurrent Rhabdoid Tumor of the Kidney|Recurrent Rhabdomyosarcoma|Recurrent Soft Tissue Sarcoma|Recurrent Thyroid Gland Carcinoma|Recurrent WHO Grade II Glioma|Refractory Adrenal Gland Pheochromocytoma|Refractory Ependymoma|Refractory Ewing Sarcoma|Refractory Hepatoblastoma|Refractory Langerhans Cell Histiocytosis|Refractory Malignant Germ Cell Tumor|Refractory Malignant Glioma|Refractory Medulloblastoma|Refractory Melanoma|Refractory Neuroblastoma|Refractory Non-Hodgkin Lymphoma|Refractory Osteosarcoma|Refractory Peripheral Primitive Neuroectodermal Tumor|Refractory Rhabdoid Tumor|Refractory Rhabdoid Tumor of the Kidney|Refractory Rhabdomyosarcoma|Refractory Soft Tissue Sarcoma|Refractory Thyroid Gland Carcinoma|Refractory WHO Grade II Glioma National Cancer Institute (NCI) July 13 2020 Phase 2
NCT03719690 Recruiting Drug: Tipifarnib|Device: HRAS Detection Assay HRAS Gene Mutation|HNSCC Kura Oncology Inc. November 5 2018 Phase 2
NCT03496766 Recruiting Drug: Tipifarnib Non Small Cell Lung Cancer Spanish Lung Cancer Group May 7 2018 Phase 2
NCT02807272 Completed Drug: Tipifarnib Leukemia Myelomonocytic Chronic Kura Oncology Inc. October 2016 Phase 2

(data from https://clinicaltrials.gov, updated on 2022-01-17)

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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