(Rac)-Lonafarnib
(Rac)-Lonafarnib (Sch66336 racemate) is an isomer of Lonafarnib (HY-15136). Lonafarnib (Sch66336) is an orally active, blood-brain barrier penetrant farnesyltransferase (FPTase) inhibitor. Lonafarnib increases the phosphorylation levels of Akt, CaMKII and CREB, upregulates BDNF expression in the hippocampus, elevates the content of α7nAChR on cell membranes, and blocks the isoprenylation of H-Ras. Lonafarnib repairs synapses and reverses spatial memory deficits in Aβ1-42 model mice. Lonafarnib inhibits RSV fusion and replication, and alleviates virus-induced lung injury. Lonafarnib activates the lysosomal and autophagic pathways, and reduces the phosphorylation and aggregation of tau. Lonafarnib acts synergistically with Sorafenib (HY-10201) to promote apoptosis, and inhibits the proliferation and invasion of melanoma cells. Lonafarnib inhibits the farnesylation of progerin, repairs nuclear membrane defects, and activates the cGAS-STING-STAT1 signaling pathway. Lonafarnib can be used in research related to diseases including Alzheimer's disease, viral infections, melanoma, and progeria.
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- CAS No.: 193275-86-4
- Formule: C27H31Br2ClN4O2
- Masse moléculaire:638.82
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Chemical Information
- Protocole
- Pureté et documentation
- Références
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Help & FAQs
Activité biologique
Description
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STAT1 |
Bcl-2 |
H-Ras |
Akt |
In Vitro
Lonafarnib inhibits RSV A2 infection in HEp-2 cells via a farnesyltransferase-independent mechanism[2].
Lonafarnib (3.3 μM; pre (-2-0 h), during (0-2 h), and post (2-16 h) infection) blocks RSV A2 infection in HEp-2 cells primarily by inhibiting the viral entry process, with significant inhibitory effects observed during the 0-2 h entry window or over the full −2-22 h period[2].
Lonafarnib inhibits RSV entry into HEp-2 cells and suppresses RSV F-induced intercellular fusion in HEK293T cells, confirming that it targets the RSV membrane fusion process[2].
Lonafarnib (0.1-0.5 μM; 48 h) stimulates endosomal microautophagy in NIH3T3 mouse fibroblasts, promoting the transport of substrates to late endosomal compartments and their degradation[3].
Lonafarnib (10 μM; 9 days) reduces the level of phosphorylated tau (Thr181) in wild-type and MAPTR406W mutant human induced pluripotent stem cell-derived neurons[3].
Lonafarnib (5 μM; 48-72 h) combined with 4 μM Sorafenib (HY-10201) synergistically suppresses the proliferation of BLM, MV3, MEWO and SKMel1 human metastatic melanoma cell lines, strengthens growth inhibition on primary melanoma cells derived from human skin metastases and reduces BLM cell viability[4].
Lonafarnib (5 μM; 24 h) inhibits the mTOR pathway in human metastatic melanoma cells. When combined with Sorafenib, it significantly downregulates intracellular Bcl-2, completely eliminates Mcl-1, and only slightly alters Bcl-xL expression[4].
Lonafarnib (3 μM; 14 days) reduces the invasion and proliferation of BL melanoma cells in organotypic skin models, and the combination with 2 μM Sorafenib completely blocks the invasion and proliferation of these cells[4].
Lonafarnib (5 μM; 24 h) combined with Sorafenib triggers typical apoptotic morphological features such as cell fragmentation in human metastatic melanoma BLM cells[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Chemical Information
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CAS No. 193275-86-4
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Masse moléculaire 638.82
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Formule C27H31Br2ClN4O2
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SMILES
O=C(N1CCC(CC(N2CCC(C3C4=C(Br)C=C(Cl)C=C4CCC5=CC(Br)=CN=C53)CC2)=O)CC1)N
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Synonyms
Sch66336 racemate
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
[1]. Cai C, et al. Ras Inhibitor Lonafarnib Rescues Structural and Functional Impairments of Synapses of Aβ Mice via α7nAChR-Dependent BDNF Upregulation. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2022 Aug 03;42(31):6090-6107. [Content Brief]
[2]. Yang Q, et al. Farnesyltransferase inhibitor lonafarnib suppresses respiratory syncytial virus infection by blocking conformational change of fusion glycoprotein. Signal transduction and targeted therapy. 2024 Jun 10;9(1):144. [Content Brief]
[3]. Hernandez I, et al. A farnesyltransferase inhibitor activates lysosomes and reduces tau pathology in mice with tauopathy. Science translational medicine. 2019 Mar 27;11(485):eaat3005. [Content Brief]
[4]. Niessner H, et al. The farnesyl transferase inhibitor lonafarnib inhibits mTOR signaling and enforces sorafenib-induced apoptosis in melanoma cells. The Journal of investigative dermatology. 2011 Feb;131(2):468-79. [Content Brief]
[5]. Arnold R, et al. Baricitinib, a JAK-STAT Inhibitor, Reduces the Cellular Toxicity of the Farnesyltransferase Inhibitor Lonafarnib in Progeria Cells. International journal of molecular sciences. 2021 Jul 12;22(14):7474. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
(Rac)-Lonafarnib Related Classifications
HY-15136B Related Classifications
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Keywords
- (Rac)-Lonafarnib
- 193275-86-4
- Sch66336
- Sch 66336
- Sch-66336
- Farnesyl Transferase
- Tau Protein
- RSV
- Akt
- Ras
- Bcl-2 Family
- STAT
- nAChR
- Apoptosis
- Autophagy
- Drug Isomer
- α7nAChR
- tau inclusions
- Hutchinson-Gilford progeria syndrome
- Alzheimer’s disease
- Aβ1-42 mice
- farnesyltransferase
- respiratory syncytial virus
- melanoma
- HEp-2 cells
- hippocampal BDNF
- Inhibitor
- inhibitor
- inhibit