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Lonidamine

Cat. No. M1923
Lonidamine Structure
Synonym:

AF 1890

Size Price Availability Quantity
10mg USD 75 In stock
50mg USD 200 In stock
200mg USD 320 In stock
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Quality Control
Biological Activity

Lonidamine is an orally administered small molecule hexokinase inactivator, an anticancer and antispermatogenic agent in vitro and in vivo. Lonidamine inhibits cellular energy metabolism in some cells via inhibition of mitochondrial hexokinase. It also blocks CFTR Cl- channels in vitro. Lonidamine could reduce the dose of temozolomide required for radiosensitization of brain tumours. Lonidamine elicits ERK and Akt/mTOR pathway activation, as indicated by increased ERK, Akt, p70S6K and rpS6 phosphorylation, and these effects are reduced by co-treatment with the anti-leukemic agent arsenic trioxide. Lonidamine significantly extends both median and maximum lifespan of C. elegans when applied at a concentration of 5 micromolar by 8% each. Lonidamine, a dechlorinate derivative of indazole-3-carboxylic acid, has proved to exert a powerful antiproliferative effect and to impair the energy metabolism of neoplastic cells.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information
Molecular Weight 321.16
Formula C15H10Cl2N2O2
CAS Number 50264-69-2
Purity >99%
Solubility DMSO
Storage at -20°C
Customer Product Validations & Biological Datas
Source Uinversity of Bergen thesis (2016). Figure 14.Lonidamine (AbMole BioScience, CAS No.: 50264-69-2)
Method WST-1 assay
Cell Lines HL60, MOLM13, NB4, and PBMC cells
Concentrations 1~100 µM
Incubation Time 48 h
Results An overall higher degree of reduced metabolic activity was observed from three independent studies with MOLM13 (Figure 14A) and NB4 (Figure14B) cells thus were suggested being more responsive to co-treatment. HL60 cells responded revealed low response to both drugs alone,resulting in only 10-25 % reduced proliferation when exposed to the highest concentrations of VPA (1 mM) and LND (100 µM), respectively (Figure 14C).
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Source Uinversity of Bergen thesis (2016). Figure 13.Lonidamine (AbMole BioScience, CAS No.: 50264-69-2)
Method Cell viability assay
Cell Lines HL60, MOLM13, NB4, and PBMC cells
Concentrations 1~100 µM
Incubation Time 48 h
Results These data indicated a comparable trend of viability in all three cell lines following combinatorial treatment of VPA and LND (Figure 13B, C). HL60 cells are only presented for Hoechst viability scoring in figure 13A since the cells do not expose phosphatidylserine upon apoptosis induction.
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Source Uinversity of Bergen thesis (2016). Figure 12.Lonidamine (AbMole BioScience, CAS No.: 50264-69-2)
Method MST-1 proliferation assay
Cell Lines HL60 cells
Concentrations 50 and 100 µM
Incubation Time 48 or 72 h
Results Maximal potentiation of LND was obtained by 100 µM LND in the sequence VPA  LND+VPA, but no significant increased anti-proliferative effect was obtained from three independent and replicable studies.
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Source Uinversity of Bergen thesis (2016). Figure 11.Lonidamine (AbMole BioScience, CAS No.: 50264-69-2)
Method Hoechst 33342 staining
Cell Lines HL60, MOLM13 and NB5 cells
Concentrations 0~500 µM
Incubation Time 24 or 48 h
Results LND elicits potential of inducing apoptosis after both 24 hours and 48 hour incubation at higher concentrations (> 50 µM) in HL60, MOLM13 and NB4 (Figure 11A-B). Apoptotic cells in the stage of morphological changes such as fragmented or condensed nuclei are shown in Figure 11C, visualized by fluorescence microscopy.
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Source Uinversity of Bergen thesis (2016). Figure 10.Lonidamine (AbMole BioScience, CAS No.: 50264-69-2)
Method WST-1 proliferation assay
Cell Lines HL60, MOLM13, NB4, and PBMC cells
Concentrations 0~1000 µM
Incubation Time 48 h
Results The distinct response of PBMC comparable to MOLM13 and HL60 is noticeably demonstrated in Figure 10A. NB4 was significantly (P<0.05) more sensitive to LND under 24 hours of exposure than 48 hours (5 – 500 µM). The IC50 of LND in NB4 (201 µM), HL60 (248 µM) and MOLM13 (124 µM) are presented in Figure 10 B, C and D indicating LND to be more effective after 48 hour treatment in MOLM13 and NB4 cells at lower concentrations than when treated for 24 hours.
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Source Uinversity of Bergen thesis (2016). Figure 9.Lonidamine (AbMole BioScience, CAS No.: 50264-69-2)
Method WST-1 proliferation assay
Cell Lines HL60, MOLM13, NB4, and PBMC cells
Concentrations 0~1000 µM
Incubation Time 24 h
Results No significant difference (P>0.05) in reduced metabolically active cells was obtained between HL60 and NB4 cells after 24 hour treatment with LND. IC50s of LND was obtained from WST-1 proliferation assay, and are presented in Figure 9B, C and D for HL60 (149 µM), MOLM13 (218 µM) and NB4 (203 µM), respectively. A wider 95% CI is observed for the IC50 of LND in treated NB4 cells (Figure 9D) than for HL60 and MOLM13, thus we cannot exclude the possibility that the IC50 of NB4 could be present anywhere between 106 – 387 µM.
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Source Uinversity of Bergen thesis (2016). Figure 7.Lonidamine (AbMole BioScience, CAS No.: 50264-69-2)
Method WST-1 assay
Cell Lines NB4 cells
Concentrations 12.5, 25, 50, 75 and 100 µM
Incubation Time 48 h
Results The combined effect of HU and MMF, shown in Figure 7A, followed the same anti-proliferative response to that of MMF alone and no additive effect or synergism was achieved. As both HK1 and HPRT1 were down-regulated by VPA in BNML rats, the combination of LND and MMF (Figure 7B) was investigated for potential synergistic or additive effect on proliferation and apoptosis.
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References

Increased apoptotic efficacy of lonidamine plus arsenic trioxide combination in human leukemia cells. Reactive oxygen species generation and defensive protein kinase (MEK/ERK, Akt/mTOR) modulation.
Calviño E, et al. Biochem Pharmacol. 2011 Dec 1;82(11):1619-29. PMID: 21889928.

Lonidamine: efficacy and safety in clinical trials for the treatment of solid tumors.
Di Cosimo S, et al. Drugs Today (Barc). 2003 Mar;39(3):157-74. PMID: 12730701.

Mechanism of lonidamine inhibition of the CFTR chloride channel.
Gong X, et al. Br J Pharmacol. 2002 Nov;137(6):928-36. PMID: 12411425.

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  Catalog
Abmole Inhibitor Catalog 2017




Keywords: Lonidamine, AF 1890 supplier, CFTR, inhibitors

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