Journal: Acta Pharmaceutica Sinica. B

Article Title: Peptidomimetic-based antibody surrogate for HER2

doi: 10.1016/j.apsb.2021.04.016

Figure Lengend Snippet: (A) Schematic presentation of one-bead-two-compounds TentalGel beads for library. (B) Scheme for the synthesis of OBTC cyclic γ -AApeptides library. (a) Soak in water for overnight; (b) (Boc) 2 O, DCM/ether; (c) Fmoc-Met-OH, HOBt, DIC, DMF; (d) deprotect Fmoc by 20% piperidine in DMF; (e) split into five portions equally; (f) Dde protected amino acids, PyBOP, NEM, DMF; (g) deprotect Boc by TFA/triisopropylsilane/H 2 O/Thioanisole (94:2:2:2); (h) Fmoc protected γ -AApeptides, HOBt, DIC, DMF; (i) deprotecting alloc by Pd(PPh 3 ) 4 and Me 2 NH·BH 3 in DCM; (j) Dmt protected mercaptopropionic acid, HOBt, DIC, DMF; (k) deprotecting Dde by NH 2 OH . HCl and imidazole in NMP/DCM (5:1); (l) split-and-pool synthesis, repeating the previous steps; (m) deprotecting Fmoc by 20% piperidine in DMF; (n) 4-(bromomethyl)benzoyl chloride, DIPEA, DCM; (o) deprotecting Dmt by TFA/triisopropylsilane/DCM (2:2:96); (p) (NH 4 ) 2 CO 3 , DMF/H 2 O (1:1). Xs are regular α -amino acids. (C) Scheme showing the overall strategy involved in library screening against HER2.

Article Snippet: HER2 was purchased from Creative BioMart; Anti-phospho-HER2 antibody was purchased from Thermo Fisher Scientific; Anti-phospho-AKT and Anti-phospho-ERK antibodies were from Cell Signaling Technology; GAPDH loading control monoclonal antibody was purchased from Invitrogen.

Techniques: Library Screening

Journal: Acta Pharmaceutica Sinica. B

Article Title: Peptidomimetic-based antibody surrogate for HER2

doi: 10.1016/j.apsb.2021.04.016

Figure Lengend Snippet: (A) Signal transduction pathway mediated by HER2 and proposed inhibition by cyclic peptides monomer and dimer. (B) Western blot analyses of SKBR3 cell lysates following M-3-6 incubation in vitro . M-3-6 treatment resulted in a dose-dependent inhibition of HER2 receptor phosphorylation and a reduction in the phosphorylation of AKT and ERK, downstream signaling of HER2. (C) Western blot analyses of SKBR3 cell lysates following M-3-6-D incubation in vitro . M-3-6-D treatment resulted in a much more effective phosphorylation inhibition compared with M-3-6. (D) M-3-6 and M-3-6-D inhibit cell proliferation. EGF-driven proliferation of SKBR3 cells was analyzed by CCK-8 proliferation assay. EGF (100 ng/mL) induced the proliferation of cells under serum-starved conditions ( ### P < 0.001 vs . non-stimulated cells), and both M-3-6 and M-3-6-D inhibited EGF-induced proliferation significantly in a dose-dependent manner (∗ P < 0.05 vs . EGF-stimulated cells, ∗∗∗ P < 0.001 vs . EGF-stimulated cells).

Article Snippet: HER2 was purchased from Creative BioMart; Anti-phospho-HER2 antibody was purchased from Thermo Fisher Scientific; Anti-phospho-AKT and Anti-phospho-ERK antibodies were from Cell Signaling Technology; GAPDH loading control monoclonal antibody was purchased from Invitrogen.

Techniques: Transduction, Inhibition, Western Blot, Incubation, In Vitro, Phospho-proteomics, CCK-8 Assay, Proliferation Assay

Journal: Acta Pharmaceutica Sinica. B

Article Title: Peptidomimetic-based antibody surrogate for HER2

doi: 10.1016/j.apsb.2021.04.016

Figure Lengend Snippet: Therapeutic efficacy of M-3-6 and M-3-6-D in SKBR3 xenograft models. (A) Mice body weight shift curve of the mice during the experiment. Arrows indicate the time of compounds treatment. (B) Time course assessment of total tumor volume. The day when treatment started was recorded as day 0 and arrows indicate the time of injection. After 2 weeks injection, tumor volume was measured once every 3 days until Day 24. (C) Immunohistochemical staining for P-HER2, P-AKT and P-ERK. Representative staining of section from SKBR3 tumors with antibodies against the indicated proteins. Scale bar: 100 nm.

Article Snippet: HER2 was purchased from Creative BioMart; Anti-phospho-HER2 antibody was purchased from Thermo Fisher Scientific; Anti-phospho-AKT and Anti-phospho-ERK antibodies were from Cell Signaling Technology; GAPDH loading control monoclonal antibody was purchased from Invitrogen.

Techniques: Drug discovery, Injection, Immunohistochemical staining, Staining

Journal: Nature Communications

Article Title: Super-enhancer-based identification of a BATF3/IL-2R−module reveals vulnerabilities in anaplastic large cell lymphoma

doi: 10.1038/s41467-021-25379-9

Figure Lengend Snippet: a OS of pediatric ALCL, ALK + patients (NHL-BFM cohort, n = 88), and b EFS and OS of adult ALCL, ALK − patients without SCT ( n = 34) having low (staining intensity, SI = 0–2) or high (SI = 3) IL-2Rα expression. Kaplan–Meier curves of individual groups were compared using two-tailed log-rank statistics. c Indicated 9 ALCL cell lines and 2 T-cell leukemia-derived control cell lines were incubated for 96 h with different concentrations of PDB dimer linked antibodies targeting either IL-2Rα (ADCT-301) or, as a non-binding control, the glycoprotein gp120 of HIV (B12-SG3249) to determine the LD 50 . Means ± SD of biological triplicates are shown. d In vivo anti-tumor efficacy of ADCT-301 in murine xenograft models of Mac-2A (ALK − ) or TLBR-1 (BIA) ALCL cell lines. For each cell line, mice were randomized into three groups to receive a single dose of either vehicle (PBS, n = 4), control ADC (B12-SG3249, 0.5 mg/kg, n = 5), or ADCT-301 (0.5 mg/kg, n = 5) intravenously at day 1 (indicated by an arrow). Tumor volumes were measured with caliper over time and are shown as means ± SEM. P values were determined by two-tailed unpaired Student’s t test. e Schematic illustration of the proposed mechanism.

Article Snippet: When tumor volumes reached ~100–150 mm 3 , mice were randomly allocated into three groups to receive vehicle (PBS), non-binding ADC (B12-SG3249) or ADCT-301 (camidanlumab tesirine) (both ADC Therapeutics, 0.5 mg/kg, intravenous injection).

Techniques: Staining, Expressing, Two Tailed Test, Derivative Assay, Control, Incubation, Binding Assay, In Vivo

Journal: Nature Reviews. Drug Discovery

Article Title: The clinical impact of glycobiology: targeting selectins, Siglecs and mammalian glycans

doi: 10.1038/s41573-020-00093-1

Figure Lengend Snippet: Selected clinical trials of glycobiology-targeted therapeutics a

Article Snippet: Monoclonal antibody MVT-5873 (clone 5B1 anti-CA19-9); MabVax Therapeutics , Pancreatic cancer , Phase I ongoing , Estimated completion in 2020 , NCT02672917.

Techniques: Clinical Proteomics, Cream, Activation Assay, Recombinant, Glycoproteomics, Vaccines, Produced, Generated, Expressing, Imaging