Journal: Journal of Medicinal Chemistry

Article Title: RTx-303, an Orally Bioavailable Polθ Polymerase Inhibitor That Potentiates PARP Inhibitors in BRCA Mutant Tumors

doi: 10.1021/acs.jmedchem.5c00551

Figure Lengend Snippet: Cellular and in vitro activity of RTx-284. A. Bar plot showing the IC50 of RTx-284 in the indicated HR-proficient (gray) and HRD (red) cell lines. Data represent mean of at least 3 independent experiments performed in triplicate. B-D. Synergy plots created by Combenefit showing synergistic activity between RTx-284 and indicated PARPi in the indicated HRD cell lines. E. Bar plot showing that 10 μM RTx-284 suppresses the MMEJ GFP reporter. Data represent mean of 3 individual experiments performed in triplicate ±SEM. F. Dot plot showing increase of γH2AX following RTx-284:olaparib treatment in DLD1 BRCA2–/– cells. G. Bar plot showing that RTx-284 promotes an increase in caspase positive DLD1 BRCA2–/– cells. Data represent mean of 3 independent experiments performed in triplicate, ±SEM.

Article Snippet: HCT 116 BRCA2 −/– and HCT 116 Parental were obtained from Cancertools, London, UK.

Techniques: In Vitro, Activity Assay

Journal: Journal of Medicinal Chemistry

Article Title: RTx-303, an Orally Bioavailable Polθ Polymerase Inhibitor That Potentiates PARP Inhibitors in BRCA Mutant Tumors

doi: 10.1021/acs.jmedchem.5c00551

Figure Lengend Snippet: RTx-303 potentiates PARPi in BRCA mutant cells and xenografts. A. Scatter plot showing relative viability of the indicated ID8 cells treated with the indicated concentrations of olaparib with and without 5 μM RTx-303. Data represent mean of 3 independent experiments performed in triplicate, ±SEM. B. Scatter plot showing BRCA2 mutant BR-05–0566 PDX volumes following treatment with vehicle, 45 mg/kg olaparib (PO,QD), 60 mg/kg RTx-303 (PO,BID), and 45 mg/kg olaparib (PO,QD) with 60 mg/kg RTx-303 (PO,BID) (left). Scatter plot showing % body weight change (right). Data represent mean, n = 7 ±SEM. C. Scatter plot showing BRCA2 mutant BR-05–0568 PDX volumes following treatment with vehicle, 0.12 mg/kg talazoparib (PO,QD) with and without 60 mg/kg RTx-303 (PO,BID) (left). Scatter plot showing % body weight change. (right). Data represent mean, n = 6 ±SEM. D. Scatter plot showing MDA-MB-436 tumor volumes following treatment with vehicle, 45 mg/kg olaparib (PO,QD) with and without 60 mg/kg RTx-303 (PO,BID) (left). Scatter plot showing % body weight change (right). Data represent mean, n = 8 ±SEM. * p < 0.05, *** p < 0.001.

Article Snippet: HCT 116 BRCA2 −/– and HCT 116 Parental were obtained from Cancertools, London, UK.

Techniques: Mutagenesis

Journal: Cell Death & Disease

Article Title: Di (2-ethylhexyl) phthalate exposure impairs meiotic progression and DNA damage repair in fetal mouse oocytes in vitro

doi: 10.1038/cddis.2017.350

Figure Lengend Snippet: Exposure to DEHP impairs DNA repair in oocytes. ( a ) Immunolabeling of the oocyte chromosomes with anti-SYCP3 (red) and anti-BRCA1 (green) antibodies. ( b ) Percentage of BRCA1 positive oocytes after six days of culture with or without DEHP ( c ) Percentage of oocytes at the pachytene and diplotene stages showing negative or positive BRCA1 staining after 6 days of culture with or without DEHP. (* P <0.05; ** P <0.01)

Article Snippet: Blocking was performed by dipping the slides in antibody dilution buffer (ADB; 0.3% BSA, 10% normal goat serum and 0.005% Triton-X-100 in TBS) for 30 min before incubation in primary antibody, anti-SCP3 at a dilution of 1:150 (Abcam, ab97672, San Francisco, CA, USA; or Novus, NB300-232, Littleton, CO, USA), anti- γ H2AX at a dilution of 1:150 (Abcam, ab26350), anti-RAD51 at a dilution of 1:150 (Abcam, ab133534), BRCA1 at a dilution of 1:100 (Boster, PB9015, Wuhan, China), or anti-MLH1 at a dilution of 1:150 (BD Pharmingen, 551091, Franklin Lakes, NJ, USA) for 3 h at 37 °C.

Techniques: Immunolabeling, Staining

Journal: Molecules

Article Title: Evaluation of In Vivo Prepared Albumin-Drug Conjugate Using Immunoprecipitation Linked LC-MS Assay and Its Application to Mouse Pharmacokinetic Study

doi: 10.3390/molecules28073223

Figure Lengend Snippet: Structure of MAC glucuronide phenol linked SN-38 ((2S,3S,4S,5R,6S)-6-(4-(((((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano [3′,4′:6,7]indolizino [1,2-b]quinolin-9-yl)oxy)methyl)(2-(methylsulfonyl)ethyl)carbamoyl)oxy)methyl)-2-(2-(3-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-N-methylpropanamido)acetamido)phenoxy)-3,4,5-trihydroxytetra-hydro-2H-pyran-2-carboxylic acid).

Article Snippet: MAC glucuronide phenol linked SN-38, and SN-38 was purchased from MedChem Express (Monmouth Junction, NJ, USA).

Techniques:

Journal: Molecules

Article Title: Evaluation of In Vivo Prepared Albumin-Drug Conjugate Using Immunoprecipitation Linked LC-MS Assay and Its Application to Mouse Pharmacokinetic Study

doi: 10.3390/molecules28073223

Figure Lengend Snippet: Representative calibration curve of SN-38 released from MAC glucuronide phenol linked SN-38.

Article Snippet: MAC glucuronide phenol linked SN-38, and SN-38 was purchased from MedChem Express (Monmouth Junction, NJ, USA).

Techniques:

Journal: Molecules

Article Title: Evaluation of In Vivo Prepared Albumin-Drug Conjugate Using Immunoprecipitation Linked LC-MS Assay and Its Application to Mouse Pharmacokinetic Study

doi: 10.3390/molecules28073223

Figure Lengend Snippet: Intra/inter-day accuracy and precision of MAC glucuronide phenol linked SN-38 in quality control samples at three levels ( n = 3 for intra-day accuracy and precision; n = 9 for inter-day accuracy and precision).

Article Snippet: MAC glucuronide phenol linked SN-38, and SN-38 was purchased from MedChem Express (Monmouth Junction, NJ, USA).

Techniques: Control, Concentration Assay

Journal: Molecules

Article Title: Evaluation of In Vivo Prepared Albumin-Drug Conjugate Using Immunoprecipitation Linked LC-MS Assay and Its Application to Mouse Pharmacokinetic Study

doi: 10.3390/molecules28073223

Figure Lengend Snippet: The stability assessment of MAC glucuronide phenol linked SN-38 in mouse plasma ( n = 3).

Article Snippet: MAC glucuronide phenol linked SN-38, and SN-38 was purchased from MedChem Express (Monmouth Junction, NJ, USA).

Techniques: Clinical Proteomics, Concentration Assay

Journal: Molecules

Article Title: Evaluation of In Vivo Prepared Albumin-Drug Conjugate Using Immunoprecipitation Linked LC-MS Assay and Its Application to Mouse Pharmacokinetic Study

doi: 10.3390/molecules28073223

Figure Lengend Snippet: Plasma stability test result of albumin conjugated MAC glucuronide phenol linked SN-38 in mouse and human plasma.

Article Snippet: MAC glucuronide phenol linked SN-38, and SN-38 was purchased from MedChem Express (Monmouth Junction, NJ, USA).

Techniques: Clinical Proteomics

Journal: Molecules

Article Title: Evaluation of In Vivo Prepared Albumin-Drug Conjugate Using Immunoprecipitation Linked LC-MS Assay and Its Application to Mouse Pharmacokinetic Study

doi: 10.3390/molecules28073223

Figure Lengend Snippet: Pharmacokinetic profiles of SN-38 at 1 mg/kg and albumin conjugated SN-38 at 1 mg/kg and 3 mg/kg MAC glucuronide phenol linked SN-38 after Intravenous administration.

Article Snippet: MAC glucuronide phenol linked SN-38, and SN-38 was purchased from MedChem Express (Monmouth Junction, NJ, USA).

Techniques:

Journal: Molecules

Article Title: Evaluation of In Vivo Prepared Albumin-Drug Conjugate Using Immunoprecipitation Linked LC-MS Assay and Its Application to Mouse Pharmacokinetic Study

doi: 10.3390/molecules28073223

Figure Lengend Snippet: Pharmacokinetic parameters of SN-38 at 1 mg/kg and albumin conjugated SN-38 at 1 mg/kg and 3 mg/kg of MAC glucuronide phenol linked SN-38 (as an equivalent dose of SN-38, 0.36 and 1.08 mg/kg respectively) after intravenous administration.

Article Snippet: MAC glucuronide phenol linked SN-38, and SN-38 was purchased from MedChem Express (Monmouth Junction, NJ, USA).

Techniques:

Journal: Molecules

Article Title: Evaluation of In Vivo Prepared Albumin-Drug Conjugate Using Immunoprecipitation Linked LC-MS Assay and Its Application to Mouse Pharmacokinetic Study

doi: 10.3390/molecules28073223

Figure Lengend Snippet: Dose proportionality evaluation between 1 and 3 mg/kg of MAC glucuronide phenol linked SN-38 using the power regression model.

Article Snippet: MAC glucuronide phenol linked SN-38, and SN-38 was purchased from MedChem Express (Monmouth Junction, NJ, USA).

Techniques:

Journal: Molecules

Article Title: Evaluation of In Vivo Prepared Albumin-Drug Conjugate Using Immunoprecipitation Linked LC-MS Assay and Its Application to Mouse Pharmacokinetic Study

doi: 10.3390/molecules28073223

Figure Lengend Snippet: Mechanism of SN-38 release from MAC glucuronide phenol linked SN-38 after incubation with β-glucuronidase.

Article Snippet: MAC glucuronide phenol linked SN-38, and SN-38 was purchased from MedChem Express (Monmouth Junction, NJ, USA).

Techniques: Incubation

Journal: Technology and Health Care

Article Title: H 2 S improves doxorubicin-induced myocardial fibrosis by inhibiting oxidative stress and apoptosis via Keap1-Nrf2

doi: 10.3233/THC-218020

Figure Lengend Snippet: Expression of TNF- α , TGF- β 1, IL1 β , IL6, Bcl-2, caspase-3, caspase-9, Bax protein in myocardial tissue of each group. P * < 0.05 vs Control group; P # < 0.05 vs DOX group.

Article Snippet: Doxorubicin hydrochloride was purchased from Meilun Biotech Co., Ltd., China; TGF- β (BA0290), CSE (A04496), MMP8 (BM4427), MMP16 (A05065), TIMP1 (A00561), Collagen III (A00788), and primary antibody, anti-rabbit secondary antibody were purchased from Boster Company, China; TNF- α (17590-1-AP), Keap1 (10503-2-AP), caspase-3 (19677-1-AP), Caspase-9 (10380-1-AP), Bax (50599-2-Ig), IL1 β (16806-1-AP), IL6 (21865-1-AP), COX2 (66351-1-Ig), Nrf2 (16396-1-AP), NQO1 (11451-1-AP), HO-1 (10701-1-AP), GCLC (12601-1-AP) and Bcl-2 (12789-1-AP) were purchased from Proteintech; These antibodies are diluted 1:1000.

Techniques: Expressing, Control