TC-SP 14

agonist of Sphingosine-1-Phosphate Receptor 1 (S1P1) CAS# 1257093-40-5

TC-SP 14

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Chemical structure

TC-SP 14

3D structure

Chemical Properties of TC-SP 14

Cas No. 1257093-40-5 SDF Download SDF
PubChem ID 51346934 Appearance Powder
Formula C25H20F2N2O2S M.Wt 450.5
Type of Compound N/A Storage Desiccate at -20°C
Solubility Soluble to 50 mM in DMSO with gentle warming
Chemical Name 1-[[3-fluoro-4-[5-[(2-fluorophenyl)methyl]-1,3-benzothiazol-2-yl]phenyl]methyl]azetidine-3-carboxylic acid
SMILES C1C(CN1CC2=CC(=C(C=C2)C3=NC4=C(S3)C=CC(=C4)CC5=CC=CC=C5F)F)C(=O)O
Standard InChIKey GVXGVDIXINMAAL-UHFFFAOYSA-N
Standard InChI InChI=1S/C25H20F2N2O2S/c26-20-4-2-1-3-17(20)9-15-6-8-23-22(11-15)28-24(32-23)19-7-5-16(10-21(19)27)12-29-13-18(14-29)25(30)31/h1-8,10-11,18H,9,12-14H2,(H,30,31)
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 TC-SP 14

DescriptionPotent and selective S1P1 agonist (EC50 values are 0.042 and 3.47 μM for human S1P1 and S1P3 respectively). Attenuates immune response to antigen challenge and reduces circulating blood lymphocyte counts in a rodent model of delayed-type hypersensitivity. Orally bioavailable.

TC-SP 14 Dilution Calculator

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TC-SP 14 Molarity Calculator

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Preparing Stock Solutions of TC-SP 14

1 mg 5 mg 10 mg 20 mg 25 mg
1 mM 2.2198 mL 11.0988 mL 22.1976 mL 44.3951 mL 55.4939 mL
5 mM 0.444 mL 2.2198 mL 4.4395 mL 8.879 mL 11.0988 mL
10 mM 0.222 mL 1.1099 mL 2.2198 mL 4.4395 mL 5.5494 mL
50 mM 0.0444 mL 0.222 mL 0.444 mL 0.8879 mL 1.1099 mL
100 mM 0.0222 mL 0.111 mL 0.222 mL 0.444 mL 0.5549 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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Background on TC-SP 14

EC50: 0.042 μM for hS1P1

TC-SP 14 is an agonist of Sphingosine-1-Phosphate Receptor 1 (S1P1).

Studies have revealed that the lysophospholipid sphingosine-1-phosphate (S1P1) is a pleiotropic modulator of diverse cellular processes. Such effects are reported to be mediated by the interactions of S1P with a set of paralogous G proteincoupled receptors, which are widely expressed in the immune, central nervous and cardiovascular systems.

In vitro: As a small lipophilic substituent proved equally effective to a larger substituent in reducing S1P3 activity, TC-SP 14 was screened. TC-SP 14 was found to be a potent S1P1 agonist (EC50 = 0.042 μM) with reduced activity for S1P3 (EC50 = 3.47 μM) [1].

In vivo: In Lewis rats, TC-SP 14 produced a dose-dependent reduction in circulating blood lymphocytes, which was consistent with S1P1 agonism. Moreover, statistical significance was shown at a dose of 0.3 mg/kg, and the dose fo 3.0 mg/kg led to near maximal lymphopenia. TC-SP 14 was subsequently investigated in a DTH antigen challenge model. Results showed a statistically significant reduction in ear swelling at doses of 0.3 mg/kg and higher. In addition, reduced ear swelling was found to closely track circulating lymphocyte counts [1].

Clinical trial: N/A

Reference:
[1] Lanman BA,Cee VJ,Cheruku SR et al.  Discovery of a Potent, S1P3-Sparing Benzothiazole Agonist of Sphingosine-1-Phosphate Receptor 1 (S1P1). ACS Med Chem Lett.2010 Nov 9;2(2):102-6.

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References on TC-SP 14

Pubertal development and anxiety risk independently relate to startle habituation during fear conditioning in 8-14 year-old females.[Pubmed:28383759]

Dev Psychobiol. 2017 May;59(4):436-448.

Reduced habituation to aversive stimuli has been observed during adolescence and may reflect an underlying mechanism of vulnerability for anxiety disorders. This study examined the startle reflex during a fear-learning task in 54 8-14-year-old girls. We examined the relationship between mean startle, startle habituation, pubertal development, and two measures linked to risk for anxiety: behavioral inhibition system (BIS) and the error-related negativity (ERN). Puberty, BIS, and the ERN were unrelated to mean startle; however, each measure modulated startle habituation. Greater pubertal development was associated with reduced startle habituation across the CS+ and CS-. Higher BIS related to a larger ERN, and both were associated with reduced startle habituation specifically to the CS+. All effects were independent of each other. Findings suggest that puberty alters habituation of defense system activation to both threat and safety cues, and this is independent of risk for anxiety, which uniquely impacts habituation to threat cues.

Exome Sequence Analysis of 14 Families With High Myopia.[Pubmed:28384719]

Invest Ophthalmol Vis Sci. 2017 Apr 1;58(4):1982-1990.

Purpose: To identify causal gene mutations in 14 families with autosomal dominant (AD) high myopia using exome sequencing. Methods: Select individuals from 14 large Caucasian families with high myopia were exome sequenced. Gene variants were filtered to identify potential pathogenic changes. Sanger sequencing was used to confirm variants in original DNA, and to test for disease cosegregation in additional family members. Candidate genes and chromosomal loci previously associated with myopic refractive error and its endophenotypes were comprehensively screened. Results: In 14 high myopia families, we identified 73 rare and 31 novel gene variants as candidates for pathogenicity. In seven of these families, two of the novel and eight of the rare variants were within known myopia loci. A total of 104 heterozygous nonsynonymous rare variants in 104 genes were identified in 10 out of 14 probands. Each variant cosegregated with affection status. No rare variants were identified in genes known to cause myopia or in genes closest to published genome-wide association study association signals for refractive error or its endophenotypes. Conclusions: Whole exome sequencing was performed to determine gene variants implicated in the pathogenesis of AD high myopia. This study provides new genes for consideration in the pathogenesis of high myopia, and may aid in the development of genetic profiling of those at greatest risk for attendant ocular morbidities of this disorder.

Efficacy and Tolerance of Cetuximab Alone or Combined with Chemotherapy in Locally Advanced or Metastatic Cutaneous Squamous Cell Carcinoma: An Open Study of 14 Patients.[Pubmed:28384639]

Dermatology. 2016;232(6):721-730.

BACKGROUND/AIMS: Previous reports highlighted the potential interest of cetuximab alone or in combination with chemotherapy in locally advanced or metastatic cutaneous squamous cell carcinomas (cSCC) care. MATERIAL AND METHODS: To further evaluate the efficiency and safety of cetuximab in advanced cSCC, a single-center retrospective study including all patients treated with cetuximab alone or combined with carboplatin for locally advanced or metastatic cSCC was conducted in a tertiary referral center. The primary end point was the overall response rate (ORR) after 2 cycles of treatment. Secondary end points were best overall disease control rate (DCR), overall survival (OS), best response duration, progression-free survival (PFS), and toxicity profile. RESULTS: Of the 14 enrolled patients, no complete response was obtained after 2 cycles of treatment, but 3 partial responses and 6 stable diseases were observed. ORR and DCR were 21.4 and 64.3%, respectively. Median OS and PFS were 9.25 and 2.65 months, respectively. Median PFS was longer with combined treatment compared with cetuximab monotherapy (9.03 vs. 3.55 months). The safety profile was acceptable with a trend toward a relationship between acne-like rash and longer response (median PFS 5.2 vs. 2.2 months). DISCUSSION/CONCLUSION: In all series including ours, disease control is usually rapidly obtained with cetuximab alone or combined with conventional chemotherapy, although with a minority of partial responses and no complete response. However, this control is of short duration in most cases. The safety profile is acceptable. A randomized phase III trial is warranted to better assess the benefit/risk ratio.

Treatment Outcome of Carotid Artery Stenting Underwent within 14 Days of Stroke Onset - Consideration of Safety and Efficacy of Urgent Carotid Artery Stenting for Neurologically Progressing Patients.[Pubmed:28381652]

Neurol Med Chir (Tokyo). 2017 Jun 15;57(6):278-283.

As the safety and effectiveness of urgent carotid artery stenting (CAS) for neurologically progressing patients remain controversial, we retrospectively analyzed the outcome of urgent CAS based on the patients' pathophysiological condition and neuroimaging findings. We divided 71 patients who underwent CAS within 14 days of stroke onset into two groups. Group 1 (n = 35) was comprised of patients with progressing neurologic signs and a reversible ischemic penumbra on magnetic resonance images (MRI). They were treated by urgent CAS. Group 2 (n = 36) was neurologically stable and underwent prophylactic CAS. In all patients we recorded the National Institutes of Health Stroke Scale (NIHSS) score and the modified Rankin scale (mRS). Urgent CAS resulted in significant improvement in the NIHSS score, when compared before and after CAS in group 1 (5.3 +/- 4.3, P < 0.01). The rate of good outcomes (mRS 0-2 at 3 months post-CAS) was 48.6% in group 1, and 75% in group 2. The cumulative incidence of ipsilateral stroke between 31 days and 1 year was 5.9% in group 1, and 0% in group 2. The procedural complication rate was similar in both groups (group 1: 5.7%, n = 2; group 2: 5.6%, n = 2). No patient suffered a symptomatic intracerebral hemorrhage. When the pathophysiological status and neuroimaging findings are used to determine patient eligibility for urgent CAS, this treatment improve neurologic outcome and can be performed as safely as prophylactic CAS in our cohort of patients with acute ischemic stroke.

Description

Potent S1P1 receptor agonist

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