L-Alaninamide
* Please be kindly noted products are not for therapeutic use. We do not sell to patients.
| Category | Others |
| Catalog number | BBF-05675 |
| CAS | 7324-05-2 |
| Molecular Weight | 88.1 |
| Molecular Formula | C3H8N2O |
Online Inquiry
Specification
| Synonyms | H-Ala-NH2 |
| IUPAC Name | (2S)-2-aminopropanamide |
| Canonical SMILES | CC(C(=O)N)N |
| InChI | InChI=1S/C3H8N2O/c1-2(4)3(5)6/h2H,4H2,1H3,(H2,5,6)/t2-/m0/s1 |
| InChI Key | HQMLIDZJXVVKCW-REOHCLBHSA-N |
Reference Reading
1. Notch-1 and Notch-3 Mediate Hypoxia-Induced Activation of Synovial Fibroblasts in Rheumatoid Arthritis
Jianhai Chen, Wenxiang Cheng, Jian Li, Yan Wang, Jingqin Chen, Xin Shen, Ailing Su, Donghao Gan, Liqing Ke, Gang Liu, Jietao Lin, Liang Li, Xueling Bai, Peng Zhang Arthritis Rheumatol. 2021 Oct;73(10):1810-1819. doi: 10.1002/art.41748. Epub 2021 Aug 30.
Objective: To investigate the molecular mechanism of hypoxia-induced rheumatoid arthritis synovial fibroblast (RASF) activation via Notch-1 and Notch-3 signaling, and to evaluate its potential as a therapeutic target. Methods: Expression of Notch-1 intracellular domain (N1ICD), N3ICD, and hypoxia-inducible factor 1α (HIF-1α) was assessed by immunhistology in synovial tissue from patients with RA. RASFs were cultured under hypoxic conditions and normoxic conditions with or without small interfering RNAs (siRNAs), and N1ICD and N3ICD were overexpressed under normoxic conditions. Rats with collagen-induced arthritis (CIA) were administered LY411575 (inhibitor of N1ICD and N3ICD) for 15 days and 28 days, and its therapeutic efficacy was assessed by histologic and radiologic evaluation of the rat synovial tissue, and by analysis of inflammatory cytokine production in the serum of rats. Results: N1ICD, N3ICD, and HIF-1α were expressed abundantly in the synovial tissue of RA patients. HIF-1α was shown to directly regulate the expression of Notch-1 and Notch-3 genes under hypoxic conditions. Moreover, hypoxia-induced N1ICD and N3ICD expression in RASFs was blocked by HIF-1α siRNA. Notch-1 siRNA and Notch-3 siRNA inhibited hypoxia-induced RASF invasion and angiogenesis in vitro, whereas overexpression of N1ICD and N3ICD promoted these processes. In addition, Notch-1 was shown to regulate RASF migration and epithelial-mesenchymal transition under hypoxic conditions, whereas Notch-3 was shown to regulate the processes of anti-apoptosis and autophagy. Furthermore, in vivo studies in rats with CIA showed that the N1ICD and N3ICD inhibitor LY411575 had a therapeutic effect in terms of ameliorating the symptoms and severity of the disease. Conclusion: This study identified a functional link between HIF-1α, Notch-1, and Notch-3 signaling in regulating activation of RASFs and the processes involved in the pathogenesis of RA.
2. Structural basis of γ-secretase inhibition and modulation by small molecule drugs
Guanghui Yang, Rui Zhou, Xuefei Guo, Chuangye Yan, Jianlin Lei, Yigong Shi Cell. 2021 Jan 21;184(2):521-533.e14. doi: 10.1016/j.cell.2020.11.049. Epub 2020 Dec 28.
Development of γ-secretase inhibitors (GSIs) and modulators (GSMs) represents an attractive therapeutic opportunity for Alzheimer's disease (AD) and cancers. However, how these GSIs and GSMs target γ-secretase has remained largely unknown. Here, we report the cryoelectron microscopy (cryo-EM) structures of human γ-secretase bound individually to two GSI clinical candidates, Semagacestat and Avagacestat, a transition state analog GSI L685,458, and a classic GSM E2012, at overall resolutions of 2.6-3.1 Å. Remarkably, each of the GSIs occupies the same general location on presenilin 1 (PS1) that accommodates the β strand from amyloid precursor protein or Notch, interfering with substrate recruitment. L685,458 directly coordinates the two catalytic aspartate residues of PS1. E2012 binds to an allosteric site of γ-secretase on the extracellular side, potentially explaining its modulating activity. Structural analysis reveals a set of shared themes and variations for inhibitor and modulator recognition that will guide development of the next-generation substrate-selective inhibitors.
3. Anti-Aβ agents for mild to moderate Alzheimer's disease: systematic review and meta-analysis
Liming Lu, Xiaoyan Zheng, Shengwen Wang, Chunzhi Tang, Yuqing Zhang, Gaolei Yao, Jingchun Zeng, Shuqi Ge, Hao Wen, Mingzhu Xu, Gordon Guyatt, Nenggui Xu J Neurol Neurosurg Psychiatry. 2020 Dec;91(12):1316-1324. doi: 10.1136/jnnp-2020-323497. Epub 2020 Oct 12.
Objective: To assess the efficacy and safety of Aβ-targeting agents for mild to moderate Alzheimer's disease. Methods: The MEDLINE, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, ClinicalTrials.gov and the WHO's International Clinical Trials Registry Platform search portal were searched from their inception to April 2020. We generated pooled estimates using random effects meta-analyses. Results: Nineteen randomised controlled trials, of which 17 had a low risk of bias, included 12 903 participants. The meta-analysis showed no difference in the cognitive subscale of Alzheimer's Disease Assessment Scale (ADAS-Cog) between anti-Aβ drugs and placebo (mean difference (MD): 0.20, 95% CI -0.40 to 0.81; I 2=99.8%; minimal important difference 3.1-3.8 points, moderate-certainty evidence). For ADAS-Cog, results suggested that one drug that increases Aβ clearance may differ in effect (MD: -0.96, 95% CI -0.99 to -0.92) from drugs that reduce Aβ production (MD: 0.78, 95% CI 0.25 to 1.32) (interaction p<0.000001); this difference also existed in the outcome of MMSE and CDR-SOB. Compared with placebo, anti-Aβ drug-related adverse events were as follows: anxiety, depression, diarrhoea, fatigue, rash, syncope and vomit. Discussion: From current evidence, anti-Aβ interventions are unlikely to have an important impact on slowing cognitive or functional decline. Although the subgroup analysis suggested possible benefits from Aβ clearance drugs, the analysis has limited credibility, and a benefit from drugs that increase clearance, if real, is very small. Trial registration number: PROSPERO registration number CRD42019126272.
Recommended Products
| BBF-00764 | Cerebroside C | Inquiry |
| BBF-00677 | 3-Amino-3-deoxy-D-glucose | Inquiry |
| BBF-01826 | Deoxymannojirimycin | Inquiry |
| BBF-02642 | Lactonamycin | Inquiry |
| BBF-02614 | Nystatin | Inquiry |
| BBF-01825 | Loganin | Inquiry |
Bio Calculators
* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
* Total Molecular Weight:
g/mol
Tip: Chemical formula is case sensitive. C22H30N4O √ c22h30n40 ╳
