Tipifarnib

製品コードS1453 バッチS145307

化学情報

	Synonyms	R115777, IND 58359	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₂₇H₂₂Cl₂N₄O
	分子量	489.4	CAS No.	192185-72-1
Solubility (25°C)*	体外	DMSO	12 mg/mL (24.51 mM)
		Water	Insoluble
		Ethanol	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	Tipifarnib 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.
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]
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]
特徴	A potent and selective farnesyl protein transferase inhibitor with significant antitumor effects.

プロトコル(参考用のみ)

細胞アッセイ	細胞株	MACS-selected CD34+ cells
	濃度	2.5 nM, 10 nM, 25 nM and 50 nM
	反応時間	48 hours
	実験の流れ	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
動物実験	動物モデル	Female ovariectomized Ncr foxhead nude mice
	投薬量	50 mg/kg
	投与方法	Oral gavage

参考

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カスタマーフィードバック

: Data from [Data independently produced by Shock, 2014, 42(6), 570-7]

: Data from [Data independently produced by Leuk Res, 2014, 10.1016/j.leukres.2014.09.002]

: Data from [Data independently produced by J Clin Endocrinol Metab, 2013, 98(6), 2502-12]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

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
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
Bacteria Are New Targets for Inhibitors of Human Farnesyltransferase [ Front Microbiol, 2021, 12:628283]	PubMed: 34917041
The farnesyltransferase inhibitor tipifarnib protects against autoimmune hepatitis induced by Concanavalin A. [ Int Immunopharmacol, 2020, 3;83:106462]	PubMed: 32251961
Gene Essentiality Profiling Reveals Gene Networks and Synthetic Lethal Interactions with Oncogenic Ras. [ Cell, 2019, 36(2):179-193]	PubMed: 28162770

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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