ML SA1

Activator of TRPML channels CAS# 332382-54-4

ML SA1

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ML SA1

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Chemical Properties of ML SA1

Cas No. 332382-54-4 SDF Download SDF
PubChem ID 2880983 Appearance Powder
Formula C22H22N2O3 M.Wt 362.42
Type of Compound N/A Storage Desiccate at -20°C
Solubility Soluble to 20 mM in DMSO
Chemical Name 2-[2-oxo-2-(2,2,4-trimethyl-3,4-dihydroquinolin-1-yl)ethyl]isoindole-1,3-dione
SMILES CC1CC(N(C2=CC=CC=C12)C(=O)CN3C(=O)C4=CC=CC=C4C3=O)(C)C
Standard InChIKey KDDHBJICVBONAX-UHFFFAOYSA-N
Standard InChI InChI=1S/C22H22N2O3/c1-14-12-22(2,3)24(18-11-7-6-8-15(14)18)19(25)13-23-20(26)16-9-4-5-10-17(16)21(23)27/h4-11,14H,12-13H2,1-3H3
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months.
Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it.
About Packaging 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial.
2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial.
3. Try to avoid loss or contamination during the experiment.
Shipping Condition Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request.

Biological Activity of ML SA1

DescriptionActivator of TRPML channels (TRPML1, 2 and 3); does not activate TRPM2, TRPV2, TRPV3, TRPC6 or TRPA1 channels. Induces TRPML-mediated Ca2+ release from lysosomes; activity corrects trafficking defects and reduces cholesterol accumulation in Niemann-Pick type C macrophages.

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Preparing Stock Solutions of ML SA1

1 mg 5 mg 10 mg 20 mg 25 mg
1 mM 2.7592 mL 13.7961 mL 27.5923 mL 55.1846 mL 68.9807 mL
5 mM 0.5518 mL 2.7592 mL 5.5185 mL 11.0369 mL 13.7961 mL
10 mM 0.2759 mL 1.3796 mL 2.7592 mL 5.5185 mL 6.8981 mL
50 mM 0.0552 mL 0.2759 mL 0.5518 mL 1.1037 mL 1.3796 mL
100 mM 0.0276 mL 0.138 mL 0.2759 mL 0.5518 mL 0.6898 mL
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations.

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References on ML SA1

Complete genome sequence of Novosphingobium resinovorum SA1, a versatile xenobiotic-degrading bacterium capable of utilizing sulfanilic acid.[Pubmed:27851894]

J Biotechnol. 2017 Jan 10;241:76-80.

Sulfanilic acid (4-aminobenzenesulfonic acid) is a sulfonated aromatic amine widely used in chemical industries for synthesis of various organic dyes and sulfa drugs. There are quite a few microbial co-cultures or single isolates capable of completely degrading this compound. Novosphingobium resinovorum SA1 was the first single bacterium which could utilize sulfanilic acid as its sole carbon, nitrogen and sulfur source. The strain has versatile catabolic routes for the bioconversion of numerous other aromatic compounds. Here, the complete genome sequence of the N. resinovorum SA1 strain is reported. The genome consists of a circular chromosome of 3.8 Mbp and four extrachromosomal elements between 67 and 1 759.8 kbp in size. Three alternative 3-ketoadipate pathways were identified on the plasmids. Sulfanilic acid is decomposed via a modified 3-ketoadipate pathway and the oxygenases involved form a phylogenetically separate branch on the tree. Sequence analysis of these elements might provide a genetic background for deeper insight into the versatile catabolic metabolism of various aromatic xenobiotics, including sulfanilic acid and its derivatives. Moreover, this is also a good model strain for understanding the role and evolution of multiple genetic elements within a single strain.

Higher Order Chromatin Modulator Cohesin SA1 Is an Early Biomarker for Colon Carcinogenesis: Race-Specific Implications.[Pubmed:27549371]

Cancer Prev Res (Phila). 2016 Nov;9(11):844-854.

Alterations in high order chromatin, with concomitant modulation in gene expression, are one of the earliest events in the development of colorectal cancer. Cohesins are a family of proteins that modulate high-order chromatin, although the role in colorectal cancer remains incompletely understood. We, therefore, assessed the role of cohesin SA1 in colorectal cancer biology and as a biomarker focusing in particular on the increased incidence/mortality of colorectal cancer among African-Americans. Immunohistochemistry on tissue arrays revealed dramatically decreased SA1 expression in both adenomas (62%; P = 0.001) and adenocarcinomas (75%; P = 0.0001). RT-PCR performed in endoscopically normal rectal biopsies (n = 78) revealed a profound decrease in SA1 expression in adenoma-harboring patients (field carcinogenesis) compared with those who were neoplasia-free (47%; P = 0.03). From a racial perspective, colorectal cancer tissues from Caucasians had 56% higher SA1 expression than in African-Americans. This was mirrored in field carcinogenesis where healthy Caucasians expressed more SA1 at baseline compared with matched African-American subjects (73%; P = 0.003). However, as a biomarker for colorectal cancer risk, the diagnostic performance as assessed by area under ROC curve was greater in African-Americans (AUROC = 0.724) than in Caucasians (AUROC = 0.585). From a biologic perspective, SA1 modulation of high-order chromatin was demonstrated with both biophotonic (nanocytology) and chromatin accessibility [micrococcal nuclease (MNase)] assays in SA1-knockdown HT29 colorectal cancer cells. The functional consequences were underscored by increased proliferation (WST-1; P = 0.0002, colony formation; P = 0.001) in the SA1-knockdown HT29 cells. These results provide the first evidence indicating a tumor suppressor role of SA1 in early colon carcinogenesis and as a risk stratification biomarker giving potential insights into biologic basis of racial disparities in colorectal cancer. Cancer Prev Res; 9(11); 844-54. (c)2016 AACR.

Profiling Diuraphis noxia (Hemiptera: Aphididae) Transcript Expression of the Biotypes SA1 and SAM Feeding on Various Triticum aestivum Varieties.[Pubmed:28334389]

J Econ Entomol. 2017 Apr 1;110(2):692-701.

The intimate relationship between an aphid and its host is mediated by the composition of the secreted saliva. In the present study, aphid heads were sampled and transcript profiling conducted after aphids were fed on their preference host and transferred to a variety of preference and nonpreference hosts. It was found that the virulent Diuraphis noxia (Kurdjumov) (Hemiptera: Aphididae) biotype SAM was able to selectively up-regulate more transcripts when confronted with feeding on a variety of hosts, than was the case with the less virulent D. noxia biotype SA1, suggesting increased genomic regulation when coping with a stressful environment. Collectively, the observed transcriptomic changes are supported by previous findings that host changes induce significant changes in the proteome of phytophagous hemipterans, unlike in many other entomophagous generalist species. The current data suggest that highly specialized hemipterans may be able to counter plant defenses with inducible salivary transcripts with resulting protein biosynthesis, as demonstrated here.

Preliminary treatment of bovine mastitis caused by Staphylococcus aureus, with trx-SA1, recombinant endolysin of S. aureus bacteriophage IME-SA1.[Pubmed:27374909]

Vet Microbiol. 2016 Aug 15;191:65-71.

Methicillin-resistant Staphylococcus aureus (MRSA) has become a great threat to human and animal health and there is an urgent need to develop novel antibacterial agents to control this pathogen. The objective of this study was to obtain an active recombinant endolysin from the novel bacteriophage (IME-SA1), and conduct an efficacy trial of its effectiveness against bovine mastitis. We isolated a phage that was virulent and specific for S. aureus with an optimal multiplicity of infection of 0.01. Electron microscopy revealed that IME-SA1 was a member of the family Myoviridae, with an isometric head (98nm) and a long contractile tail (200nm). Experimental lysis experiments indicated the phage had an incubation period of 20min with a burst size of 80. When host bacteria were in early exponential growth stages, a multiplicity of infection of 0.01 resulted in a complete bacterial lysis after 9h. The endolysin gene (804bp) was cloned into the pET-32a bacterial expression vector and recombinant endolysin Trx-SA1 was successfully obtained with molecular size of about 47kDa. Preliminary results of therapeutic trials in cow udders showed that Trx-SA1 could effectively control mild clinical mastitis caused by S. aureus. The endolysin Trx-SA1 might be an alternative treatment strategy for infections caused by S. aureus, including MRSA.

Lipid storage disorders block lysosomal trafficking by inhibiting a TRP channel and lysosomal calcium release.[Pubmed:22415822]

Nat Commun. 2012 Mar 13;3:731.

Lysosomal lipid accumulation, defects in membrane trafficking and altered Ca(2+) homoeostasis are common features in many lysosomal storage diseases. Mucolipin transient receptor potential channel 1 (TRPML1) is the principle Ca(2+) channel in the lysosome. Here we show that TRPML1-mediated lysosomal Ca(2+) release, measured using a genetically encoded Ca(2+) indicator (GCaMP3) attached directly to TRPML1 and elicited by a potent membrane-permeable synthetic agonist, is dramatically reduced in Niemann-Pick (NP) disease cells. Sphingomyelins (SMs) are plasma membrane lipids that undergo sphingomyelinase (SMase)-mediated hydrolysis in the lysosomes of normal cells, but accumulate distinctively in lysosomes of NP cells. Patch-clamp analyses revealed that TRPML1 channel activity is inhibited by SMs, but potentiated by SMases. In NP-type C cells, increasing TRPML1's expression or activity was sufficient to correct the trafficking defects and reduce lysosome storage and cholesterol accumulation. We propose that abnormal accumulation of luminal lipids causes secondary lysosome storage by blocking TRPML1- and Ca(2+)-dependent lysosomal trafficking.

Cross-talk between TRPML1 channel, lipids and lysosomal storage diseases.[Pubmed:22808310]

Commun Integr Biol. 2012 Mar 1;5(2):111-3.

Described by the Belgian cytologist Christian De Duve in 1949,(1) lysosomes (from the Greek "digestive bodies") are ubiquitous specialized intracellular organelles that ensure the degradation/recycling of macromolecules (proteins, lipids, membranes) through the activity of specific enzymes (i.e., acid hydrolases). They receive their substrates through different internalization pathways (i.e., endocytosis, phagocytosis and autophagy) and are involved in a wide range of physiological functions from cell death and signaling to cholesterol homeostasis and plasma membrane repair.(2) In Mammals, 50 soluble lysosomal hydrolases have been described, each targeting specific substrates. They are confined in the lumen of the lysosome and require an optimum pH (i.e., pH 4.5) to work. This acidic pH compared with the slightly alkaline pH of the cytosol (i.e., ~pH 7.2) is maintained by the activity of integral lysosomal membrane proteins (LMPs, that represent the second class of lysosomal proteins), including the V-type proton (H(+))-ATPase(3) and the chloride ion channel CLC7(4) that pumps protons from the cytosol across the lysosomal membrane.

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