NN-01-195
NN-01-195 is a HSP90 and AURKA inhibitor. NN-01-195 binds tightly to and inhibits AURKA and HSP90, with an IC50 of 3.1 nM against AURKA and an IC50 of 8.7 nM against HSP90α. NN-01-195 induces mitotic arrest and spindle abnormality in tumor cells, and triggers cell apoptosis. NN-01-195 can be used in the research of solid tumors.
For research use only. We do not sell to patients.
- Formula: C56H60Cl2F4N12O5
- Molecular Weight:1128.05
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
- Protocols
- Purity & Documentation
- References
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Help & FAQs
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Biological Activity
Description
IC50 & Target
[1]|
HSP90α 8.7 nM (IC50) |
In Vitro
NN-01-195 (1-10000 nM) can efficiently enter HEK293T cells and bind to intracellular HSP90, without showing obvious cell permeability limitations[1].
NN-01-195 (0-10 μM; 24-72 hours) reduces the viability of FaDu and NCI-H1975 cells, and induces G2/M cell cycle arrest, apoptosis and mitotic spindle abnormalities[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:FaDu, NCI-H1975
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Concentration:500 and 1000 nM
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Incubation Time:72 h (cleaved PARP); 24 h (other targets)
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Result:Induced cleaved PARP (a marker of apoptosis) in FaDu and NCI-H1975 cells.
Induced total AURKA expression and reduced p-AURKA levels in FaDu cells, did not alter HSP70 or HSP60 expression, and did not reduce p-S6, total S6, p-AKT, total AKT, p-ERK, or total ERK levels.
Parmacokinetics
| Species | Dose | Route | Tmax | Cmax | T1/2 | AUClast | AUCinf |
|---|---|---|---|---|---|---|---|
| Mice[1] | 10 mg/kg | i.p. | 0.500 h | 9870 ng/mL | 1.76 h | 24114 ng·h/mL | 26494 ng·h/mL |
In Vivo
NN-01-195 (30 mg/kg; i.p.; daily; 14 days) and Adavosertib (HY-10993) inhibits the growth of FaDu xenograft tumors in mice[1].
NN-01-195 (30 mg/kg; i.p.; daily; 21 days) exerts inhibitory effects on the growth of H1975 xenograft tumors in mice[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NSG treated FaDu (6-10 weeks old, initial body weight 20-31 g)[1]
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Dosage:30 mg/kg (single-agent); 30 mg/kg (combination with 60 mg/kg adavosertib)
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Administration:i.p.; daily; 14 days
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Result:Did not cause a statistically significant reduction in tumor volume versus vehicle as a single agent.
Resulted in a statistically significant reduction in tumor volume versus vehicle, single-agent NN-01-195, single-agent adavosertib, and the VIC-1911 plus adavosertib combination when used in combination with adavosertib.
Led to a significantly lower Ki-67 H-score in tumor tissue in the NN-01-195 plus adavosertib group versus vehicle.
Caused no significant changes in body weight in any treatment group.
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Animal Model:NSG treate H1975 (6-10 weeks old, initial body weight 20-31 g)[1]
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Dosage:30 mg/kg (single-agent); 30 mg/kg (combination with 60 mg/kg Adavosertib)
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Administration:i.p.; daily; 21 days
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Result:Showed slightly better quantitative control of tumor growth versus VIC-1911 as a single agent, but this did not reach statistical significance.
Provided good tumor growth control when used in combination with adavosertib.
Caused no significant changes in body weight in any treatment group.
Chemical Information
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Molecular Weight 1128.05
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Formula C56H60Cl2F4N12O5
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SMILES
NC(C1=C(NC2=CC=C(N3CCN(C(CCCCCNC(C4(CC5=NC(NC6=NNC(C)=C6)=C(F)C=C5)CCN(C(C7=C(Cl)C(Cl)=CC=C7)=O)CC4)=O)=O)CC3)C=C2)C=C(N8C(CC(C)(C)CC9=O)=C9C(C(F)(F)F)=N8)C=C1)=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
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Detection of Apoptosis
Apoptosis, also called programmed cell death, is generally characterized by distinct morphological characteristics.
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TUNEL staining for apoptotic DNA fragmentation
TUNEL staining detects DNA strand breaks by using terminal deoxynucleotidyl transferase to add labeled nucleotides to exposed 3′-OH DNA termini, generating either microscopic staining in fixed cells or tissue sections, or fluorescence/cytometric signal in cell suspensions. TUNEL positivity reflects DNA fragmentation but should not be interpreted alone as definitive apoptosis, because TUNEL can also label necrotic, autolytic, mechanically damaged, or DNA-repair-associated DNA breaks.
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Annexin V plus membrane-impermeant dye apoptosis staining
Annexin V-based apoptosis assays rely on the detection of phosphatidylserine (PS) externalization from the inner leaflet of the plasma membrane to the outer leaflet, an early biochemical hallmark of apoptosis. Fluorescently labeled Annexin V binds PS in a calcium-dependent manner, enabling identification of early apoptotic cells by flow cytometry or fluorescence microscopy. When combined with a membrane-impermeant DNA-binding dye (e. g. , propidium iodide), this approach allows discrimination between viable (Annexin V−/dye−), early apoptotic (Annexin V+/dye−), and late apoptotic or necrotic (Annexin V+/dye+) cell populations by assessing membrane integrity and PS exposure.
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Apoptosis Solutions
Apoptosis is a regulated, generally non-lytic cell-death pathway that removes unwanted, damaged, infected, or abnormal cells through coordinated morphological changes, caspase activation, DNA fragmentation, and membrane remodeling. The intrinsic apoptosis pathway is controlled mainly by mitochondrial outer membrane permeabilization, BCL-2 family proteins, cytochrome c release, apoptosome formation, caspase-9 activation, and downstream executioner caspase-3/7 activation. The extrinsic apoptosis pathway is initiated by death receptors such as Fas, TNFR, and TRAIL receptors, which recruit adaptor proteins and activate caspase-8 before engaging executioner caspases or mitochondrial amplification through BID cleavage. Apoptosis is linked to many phenotypes, including cancer cell killing, tissue homeostasis, immune regulation, neurodegeneration, infection response, and treatment-induced cytotoxicity; unresolved questions include how apoptosis interacts with necroptosis, pyroptosis, ferroptos
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
NN-01-195 Related Classifications
HY-181626 Related Classifications
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