(S,R,S)-AHPC-amido-C5-acid - CAS 2162120-87-6

(S,R,S)-AHPC-amido-C5-acid is a synthetic E3 ligand-linker conjugate containing a von-Hippel-Lindau (VHL) ligand and a C5 alkyl linker with terminal carboxylic acid for covalent binding, which is an intermediate in the synthesis of the XY028-133 (HY-129180).

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Molecular Formula
C₂₉H₄₀N₄O₆S
Molecular Weight
572.72

(S,R,S)-AHPC-amido-C5-acid

    • Specification
      • Storage
        -20°C, sealed storage, away from moisture and light;In solvent, -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)
        Shipping
        Room temperature in continental US; may vary elsewhere.
        IUPAC Name
        7-[[(2S)-1-[(2S,4R)-4-hydroxy-2-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methylcarbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-7-oxoheptanoic acid
    • Properties
      • InChI Key
        LYAMSRXTXVKKIC-TVZXLZGTSA-N
        InChI
        1S/C29H40N4O6S/c1-18-25(40-17-31-18)20-12-10-19(11-13-20)15-30-27(38)22-14-21(34)16-33(22)28(39)26(29(2,3)4)32-23(35)8-6-5-7-9-24(36)37/h10-13,17,21-22,26,34H,5-9,14-16H2,1-4H3,(H,30,38)(H,32,35)(H,36,37)/t21-,22+,26-/m1/s1
        Canonical SMILES
        CC1=C(C2=CC=C(C=C2)CNC([C@@H]3C[C@H](CN3C([C@H](C(C)(C)C)NC(CCCCCC(O)=O)=O)=O)O)=O)SC=N1
        Pub Chem ID
        134184033
    • Reference Reading
      • 1. Modification and validation of the Birmingham Vasculitis Activity Score (version 3)
        C Mukhtyar, R Lee, D Brown, D Carruthers, B Dasgupta, S Dubey, O Flossmann, C Hall, J Hollywood, D Jayne, R Jones, P Lanyon, A Muir, D Scott, L Young, R A Luqmani Ann Rheum Dis. 2009 Dec;68(12):1827-32.doi: 10.1136/ard.2008.101279.Epub 2008 Dec 3.
        Background:Comprehensive multisystem clinical assessment using the Birmingham Vasculitis Activity score (BVAS) is widely used in therapeutic studies of systemic vasculitis. Extensive use suggested a need to revise the instrument. The previous version of BVAS has been revised, according to usage and reviewed by an expert committee. Objective:To modify and validate version 3 of the BVAS in patients with systemic vasculitis.
        2. Cholangiocarcinoma - evolving concepts and therapeutic strategies
        Sumera Rizvi, Shahid A Khan, Christopher L Hallemeier, Robin K Kelley, Gregory J Gores Nat Rev Clin Oncol. 2018 Feb;15(2):95-111.doi: 10.1038/nrclinonc.2017.157.Epub 2017 Oct 10.
        Cholangiocarcinoma is a disease entity comprising diverse epithelial tumours with features of cholangiocyte differentiation: cholangiocarcinomas are categorized according to anatomical location as intrahepatic (iCCA), perihilar (pCCA), or distal (dCCA). Each subtype has a distinct epidemiology, biology, prognosis, and strategy for clinical management. The incidence of cholangiocarcinoma, particularly iCCA, has increased globally over the past few decades. Surgical resection remains the mainstay of potentially curative treatment for all three disease subtypes, whereas liver transplantation after neoadjuvant chemoradiation is restricted to a subset of patients with early stage pCCA. For patients with advanced-stage or unresectable disease, locoregional and systemic chemotherapeutics are the primary treatment options. Improvements in external-beam radiation therapy have facilitated the treatment of cholangiocarcinoma. Moreover, advances in comprehensive whole-exome and transcriptome sequencing have defined the genetic landscape of each cholangiocarcinoma subtype. Accordingly, promising molecular targets for precision medicine have been identified, and are being evaluated in clinical trials, including those exploring immunotherapy. Biomarker-driven trials, in which patients are stratified according to anatomical cholangiocarcinoma subtype and genetic aberrations, will be essential in the development of targeted therapies. Targeting the rich tumour stroma of cholangiocarcinoma in conjunction with targeted therapies might also be useful. Herein, we review the evolving developments in the epidemiology, pathogenesis, and management of cholangiocarcinoma.
        3. Degree of Myopia and Glaucoma Risk: A Dose-Response Meta-analysis
        Ahnul Ha, Chung Young Kim, Sung Ryul Shim, In Boem Chang, Young Kook Kim Am J Ophthalmol. 2022 Apr;236:107-119.doi: 10.1016/j.ajo.2021.10.007.Epub 2021 Oct 11.
        Purpose:To verify the dose-response relation between the degree of myopia and open-angle glaucoma (OAG) risk DESIGN: Dose-response meta-analysis. Methods:We searched the PubMed, EMBASE, and Cochrane Library databases for population-based studies published until November 30, 2020, and reporting on both myopia and OAG. Random-effect models generated pooled odds ratios (OR) and 95% CIs. Results robustness was confirmed by influence and subgroup analyses. A 2-stage dose-response meta-analysis calculated the OAG risk per unit dose of myopia (spherical equivalent [SE] decrease of 1 diopter [D]) and examined the relationship pattern. Results:The meta-analysis comprised 24 studies in 11 countries (514,265 individuals). The pooled OR of any myopia degree's association with OAG was 1.88 (95% CI, 1.66-2.13; I2 = 53%). The OR differences based on ethnicity (Asians vs Westerners) or 5 geographic areas were not statistically significant (P = .80 and P = .06, respectively). The pooled ORs of the associations between low, moderate, moderate-to-high, high myopia, and OAG were 1.50 (95% CI, 1.29-1.76), 1.69 (95% CI, 1.33-2.15), 2.27 (95% CI, 1.74-2.96), and 4.14 (95% CI, 2.57-6.69), respectively. According to the dose-response meta-analysis, the pooled OR (per SE 1-D change) was 1.21 (95% CI, 1.15-1.28). The OAG risk accelerated at approximately -6 D, and further accelerated from -8 D, showing a nonlinear concave upward slope (P = .03).Conclusions:For each unit (1-D) increase in myopia, the risk of glaucoma increases by approximately 20%. The risk more steeply increases in high-degree myopia, representing a significant nonlinear relationship.
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