Tipifarnib (IND 58359)

CatalogusnummerS1453 Batch:S145303

Afdrukken

Technische gegevens

Formule

C27H22Cl2N4O
Moleculair gewicht 489.4 CAS-nr. 192185-72-1
Oplosbaarheid (25°C)* In vitro DMSO 14 mg/mL (28.6 mM)
Ethanol 9 mg/mL (18.38 mM)
Water Insoluble
In vivo (Voeg oplosmiddelen afzonderlijk en in volgorde toe aan het product.)
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <1 mg/ml betekent licht oplosbaar of onoplosbaar.
* Houd er rekening mee dat Selleck de oplosbaarheid van alle verbindingen intern test en de werkelijke oplosbaarheid enigszins kan afwijken van gepubliceerde waarden. Dit is normaal en is te wijten aan lichte batch-tot-batch variaties.
* Verzending op kamertemperatuur (Stabiliteitstests tonen aan dat dit product zonder koelmaatregelen kan worden verzonden.)

Voorbereiden van stamoplossingen

Biologische activiteit

Beschrijving Tipifarnib is een potente en specifieke farnesyltransferase (FTase) remmer met een IC50 van 0,6 nM; de antiproliferatieve effecten zijn het meest prominent in H-ras of N-ras mutante cellen. Fase 3.
Doelen
FTase
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, this compound reduces the percentage of IFNγ-positive cells in a time-dependent manner. It reduces the amount of activated Ras in precipitates compared to DMSO. This chemical 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 this compound. Combining it with 10 nM 4-OH-ICI 46474 in the presence of E2 reduces the IC50 8-fold from 400 to 50 nM. It induces apoptosis in U937 cells. In addition, this chemical 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.

In vivo

Ki-67 is lower in the tumors treated with E2 withdrawal plus this compound compared with E2 withdrawal alone. The combination of ICI 46474 and this chemical results in significantly lower Ki-67 compared with either ICI 46474 or this agent alone (mean of 5% versus 16.9% and 67.3%, respectively). In contrast, no significant difference in apoptotic scores is seen between the treatment groups. This compound alone also reduces the CTI compared with control. The combination of ICI 46474 and this agent or this chemical 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.

Kenmerken Een potente en selectieve farnesylproteïne transferase remmer met significante antitumorale effecten.

Protocol (uit referentie)

Celassay:

[4]
  • Cellijnen

    MACS-selected CD34+ cells

  • Concentraties

    2.5 nM, 10 nM, 25 nM and 50 nM

  • Incubatietijd

    48 hours

  • Methode

    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
Dierstudie:

[4]
  • Dierlijke modellen

    Female ovariectomized Ncr foxhead nude mice

  • Doseringen

    50 mg/kg

  • Toediening

    Oral gavage

Referenties

  • https://pubmed.ncbi.nlm.nih.gov/22228638/
  • https://pubmed.ncbi.nlm.nih.gov/21983879/
  • https://pubmed.ncbi.nlm.nih.gov/18824842/
  • https://pubmed.ncbi.nlm.nih.gov/17876043/
  • https://pubmed.ncbi.nlm.nih.gov/22209975/
  • https://pubmed.ncbi.nlm.nih.gov/11196150/

Klantproductvalidatie

Effects of tipifarnib on GalN/LPS-induced mortality and ALF in mice. Representative liver histology (H/E staining at 5 h after saline or GalN/LPS) by microscopic images are shown.

Gegevens van [ Shock , 2014 , 42(6), 570-7 ]

Simvastatin/tipifarnib alters subcellular localization of RAS in human leukemia cells. Leukemia cells were treated with simvastatin (4 uM) and tipifarnib (1 uM), alone and in combination for 72hrs. Cytosolic and membrane fractions were prepared and western blot analysis was performed as described in the method section using the indicated antibodies. Calnexin was used as a membrane marker, whereas GAPDH is a marker of the cytosolic fraction. SIM, simvastatin. TIP, tipifarnib.

Gegevens van [ Leuk Res , 2014 , 10.1016/j.leukres.2014.09.002 ]

Effect of the inhibition of mutated RAS on thyroid cancer cell response to gefitinib . C-643 (RAS mutated thyroid cancer cells) and BC-PAP (wild type RAS thyroid cancer cells) were seeded in 96-well plates and incubated with increasing doses of gefitinib (Gef.; 0.5, 1.0 , and 5.0 uM), the RAS inhibitor tipifarnib (0.1, 1.0 and 10 uM) or both for 48 hours. Cell viability was then measured by the MTT assay.

Gegevens van [ J Clin Endocrinol Metab , 2013 , 98(6), 2502-12 ]

The effects of SelleckChem inhibitors on sea urchin embryo development evaluated 24 h after fertilization. All compounds were added to embryos suspension 20 min after fertilization. The relative presence of late gastrula, swimming blastula, undeveloped embryos and dead embryos was compared next to untreated control embryos (A). Fertilized egg, swimming blastula and late gastrula are illustrated (B). The embryonic development was relatively synchronized in untreated control samples after 24 h (A, E). GSK690693 treatment sustained the development of embryos. Swimming blastulas kept normal motility regardless the deformities in their shape. Tipifarnib treatment induced significant toxicity due to occurrence of dead fragmented embryos. Some abnormal blastulas kept the motility. AZD2014 treatment sustained the development of embryos. Some developed gastrulas and blastulas were less motile in comparison with control (A, C). WZ811 was the least toxic compound. Significant number of gastrulas and blastulas was developed. However, their motility was considerably suppressed (A, D). In contrast to SelleckChem inhibitors, classic anticancer agent – cisplatin was extremely toxic to sea urchin embryos (A). Cisplatin killed many embryos, while a small amount of survived embryos was stopped at early phases of development: immediately after fertilization or after first and second division (A, F).

, , Dr. Milica Pesic from Institute for Biological Research

Selleck's Tipifarnib (IND 58359) Is geciteerd door 41 Publicaties

Impaired MC3T3-E1 osteoblast differentiation triggered by oncogenic HRAS is rescued by the farnesyltransferase inhibitor Tipifarnib [ Sci Rep, 2025, 15(1):6832] PubMed: 40000861
In Vitro synergy of Farnesyltransferase inhibitors in combination with colistin against ESKAPE bacteria [ PLoS One, 2025, 20(9):e0331440] PubMed: 40911556
Mitotic perturbation is a key mechanism of action of decitabine in myeloid tumor treatment [ Cell Rep, 2023, 42(9):113098] PubMed: 37714156
Salivary gland cancer organoids are valid for preclinical genotype-oriented medical precision trials [ iScience, 2023, 26(5):106695] PubMed: 37207275
Suppression of NASH-Related HCC by Farnesyltransferase Inhibitor through Inhibition of Inflammation and Hypoxia-Inducible Factor-1α Expression [ Int J Mol Sci, 2023, 24(14)11546] PubMed: 37511305
Cooperative Genomic Lesions in HRAS-Mutant Cancers Predict Resistance to Farnesyltransferase Inhibitors [ Res Sq, 2023, rs.3.rs-3154719] PubMed: 37503077
Combination of Tipifarnib and Sunitinib Overcomes Renal Cell Carcinoma Resistance to Tyrosine Kinase Inhibitors via Tumor-Derived Exosome and T Cell Modulation [ Cancers (Basel), 2022 Feb 11, 14(4):903] PubMed: 35205655
BRAF activation by metabolic stress promotes glycolysis sensitizing NRASQ61-mutated melanomas to targeted therapy [ Nat Commun, 2022, 13(1):7113] PubMed: 36402789
Impact of a conserved N-terminal proline-rich region of the α-subunit of CAAX-prenyltransferases on their enzyme properties [ Cell Commun Signal, 2022, 20(1):118] PubMed: 35941619
Combination of Tipifarnib and Sunitinib Overcomes Renal Cell Carcinoma Resistance to Tyrosine Kinase Inhibitors via Tumor-Derived Exosome and T Cell Modulation [ Cancers (Basel), 2022, 14(4)903] PubMed: 35205655

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NIET VOOR HUMANE, VETERINAIRE DIAGNOSTISCHE OF THERAPEUTISCHE DOELEINDEN.