Synonym
LYS-05 HCl; LYS05; LYS-05; Lys01 (trihydrochloride); Lys01 HCl salt.
IUPAC/Chemical Name
N2-(7-Chloro-4-quinolinyl)-N1-[2-[(7-chloro-4-quinolinyl)amino]ethyl]-N1-methyl-1,2-ethanediamine trihydrochloride
InChi Key
JTUYDBHQGOZPQQ-UHFFFAOYSA-N
InChi Code
InChI=1S/C23H23Cl2N5.3ClH/c1-30(12-10-28-20-6-8-26-22-14-16(24)2-4-18(20)22)13-11-29-21-7-9-27-23-15-17(25)3-5-19(21)23;;;/h2-9,14-15H,10-13H2,1H3,(H,26,28)(H,27,29);3*1H
SMILES Code
CN(CCNC1=CC=NC2=CC(Cl)=CC=C12)CCNC3=CC=NC4=CC(Cl)=CC=C34.[H]Cl.[H]Cl.[H]Cl
Appearance
Brown solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO and water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
Lys05 (Lys01 trihydrochloride) is a lysosomal autophagy inhibitor with IC50 values of 3.6, 3.8, 6 and 7.9 μM for 1205Lu, c8161, LN229 and HT-29 cell line in the MTT assay.
In vitro activity:
Overall, the results suggested that melanoma cells with low Wnt5A and high β–catenin have increased sensitivity to Lys05-mediated autophagy inhibition. To confirm this Wnt5Alow, β–catenin high melanoma cells (FS13 and FS14) and melanoma cells were treated with high Wnt5A and low β–catenin (FS4, FS5) with Lys05 (Figure 6A,B). Indeed, Wnt5Ahigh cells are less sensitive to Lys05 both in terms of cell viability (Figure 6B, Supplementary Figure 4A) and in terms of apoptosis as measured by Annexin V staining (Supplementary Figure 4B). Next, melanoma cells that are high in β– catenin (FS14) were treated with rWnt5A to induce Wnt5A-mediated β–catenin degradation. β–catenin activity was significantly decreased by Wnt5A as measured by Topflash® assay (figure 6C). Treating FS14 cells with rWnt5A makes the cells less sensitive to Lys05-mediated autophagy inhibition, suggesting that Wnt5A-mediated decreases in β–catenin may decrease sensitivity to Lys05 (figure 6D). These data suggest that, as with many other signaling pathways, continued activation of the pathway, in this case by a switch from canonical to non-canonical Wnt signaling can render cells less sensitive to drugs targeted to inhibit this pathway.
Reference: Cancer Res. 2017 Nov 1;77(21):5873-5885. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5718045/
In vivo activity:
In two melanoma xenograft models and a colon cancer xenograft model, intermittent high dose Lys05 or chronic daily dosing of Lys05 at lower doses produces significant early blockade of autophagy in vivo, and has single-agent antitumor activity at doses as low as 10 mg/kg i.p. daily. In contrast, single-agent high dose HCQ treatment administered intermittently does not produce clear evidence of autophagy inhibition at early time points, and is associated with tumor growth compared with control in one model. To better understand these findings, the lysosomal drug accumulation and functional deacidification of lysosomes in Lys05 and HCQ treated cells was compared. Compared with HCQ, Lys05 more potently accumulates within and deacidifies the lysosome of both cells and tumors, resulting in more sustained inhibition of autophagy and tumor growth. While even 100 µM HCQ cannot completely deacidify the endovesicular compartment in cancer cells, complete deacidification is observed with 50 µM Lys05 as evidenced by acridine orange aggregation.
Reference: Autophagy. 2012 Sep 1; 8(9): 1383–1384. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3442884/
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| DMSO |
12.0 |
21.83 |
|
| Water |
4.7 |
8.55 |
|
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
549.75
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Ndoye A, Budina-Kolomets A, Kugel CH 3rd, Webster MR, Kaur A, Behera R, Rebecca VW, Li L, Brafford PA, Liu Q, Gopal YNV, Davies MA, Mills GB, Xu X, Wu H, Herlyn M, Nicastri MC, Winkler JD, Soengas MS, Amaravadi RK, Murphy ME, Weeraratna AT. ATG5 Mediates a Positive Feedback Loop between Wnt Signaling and Autophagy in Melanoma. Cancer Res. 2017 Nov 1;77(21):5873-5885. doi: 10.1158/0008-5472.CAN-17-0907. Epub 2017 Sep 8. PMID: 28887323; PMCID: PMC5718045.
2. McAfee Q, Zhang Z, Samanta A, Levi SM, Ma XH, Piao S, Lynch JP, Uehara T, Sepulveda AR, Davis LE, Winkler JD, Amaravadi RK. Autophagy inhibitor Lys05 has single-agent antitumor activity and reproduces the phenotype of a genetic autophagy deficiency. Proc Natl Acad Sci U S A. 2012 May 22;109(21):8253-8. doi: 10.1073/pnas.1118193109. Epub 2012 May 7. PMID: 22566612; PMCID: PMC3361415.
In vitro protocol:
1. Ndoye A, Budina-Kolomets A, Kugel CH 3rd, Webster MR, Kaur A, Behera R, Rebecca VW, Li L, Brafford PA, Liu Q, Gopal YNV, Davies MA, Mills GB, Xu X, Wu H, Herlyn M, Nicastri MC, Winkler JD, Soengas MS, Amaravadi RK, Murphy ME, Weeraratna AT. ATG5 Mediates a Positive Feedback Loop between Wnt Signaling and Autophagy in Melanoma. Cancer Res. 2017 Nov 1;77(21):5873-5885. doi: 10.1158/0008-5472.CAN-17-0907. Epub 2017 Sep 8. PMID: 28887323; PMCID: PMC5718045.
In vivo protocol:
1. McAfee Q, Zhang Z, Samanta A, Levi SM, Ma XH, Piao S, Lynch JP, Uehara T, Sepulveda AR, Davis LE, Winkler JD, Amaravadi RK. Autophagy inhibitor Lys05 has single-agent antitumor activity and reproduces the phenotype of a genetic autophagy deficiency. Proc Natl Acad Sci U S A. 2012 May 22;109(21):8253-8. doi: 10.1073/pnas.1118193109. Epub 2012 May 7. PMID: 22566612; PMCID: PMC3361415.
1: Amaravadi RK, Winkler JD. Lys05: a new lysosomal autophagy inhibitor.
Autophagy. 2012 Sep;8(9):1383-4. doi: 10.4161/auto.20958. PubMed PMID: 22878685;
PubMed Central PMCID: PMC3442884.
2: McAfee Q, Zhang Z, Samanta A, Levi SM, Ma XH, Piao S, Lynch JP, Uehara T,
Sepulveda AR, Davis LE, Winkler JD, Amaravadi RK. Autophagy inhibitor Lys05 has
single-agent antitumor activity and reproduces the phenotype of a genetic
autophagy deficiency. Proc Natl Acad Sci U S A. 2012 May 22;109(21):8253-8. doi:
10.1073/pnas.1118193109. PubMed PMID: 22566612; PubMed Central PMCID: PMC3361415.
3: DeVorkin L, Hattersley M, Kim P, Ries J, Spowart J, Anglesio MS, Levi SM,
Huntsman DG, Amaravadi RK, Winkler JD, Tinker AV, Lum JJ. Autophagy Inhibition
Enhances Sunitinib Efficacy in Clear Cell Ovarian Carcinoma. Mol Cancer Res. 2016
Dec 7. pii: molcanres.0132.2016. [Epub ahead of print] PubMed PMID: 27927774.
4: Shi TT, Yu XX, Yan LJ, Xiao HT. Research progress of hydroxychloroquine and
autophagy inhibitors on cancer. Cancer Chemother Pharmacol. 2016 Nov 26. [Epub
ahead of print] Review. PubMed PMID: 27889812.
